PDR MEMBER LOGIN:
  • PDR Search

    Required field
  • Advertisement
  • CLASSES

    Amide Local Anesthetics

    DEA CLASS

    Rx

    DESCRIPTION

    Long-acting, amide-type local anesthetic; structure and kinetics are similar to bupivacaine, however, ropivacaine appears to be less arrhythmogenic.

    COMMON BRAND NAMES

    Naropin, Ropivacaine

    HOW SUPPLIED

    Naropin/Ropivacaine/Ropivacaine Hydrochloride Monohydrate Epidural Inj Sol: 0.2%, 0.5%, 0.75%, 1%
    Naropin/Ropivacaine/Ropivacaine Hydrochloride Monohydrate Infiltration Inj Sol: 0.2%, 0.5%, 0.75%, 1%

    DOSAGE & INDICATIONS

    For local anesthesia, regional anesthesia, or surgical anesthesia.
    NOTE: Doses listed below are those considered necessary to produce a successful block and should be regarded as guidelines for use in adults. Individual variations in onset and duration may occur. The dose for a major nerve block must be adjusted for the administration site and patient status.
    NOTE: Ropivacaine is not recommended for emergency situations, as a fast onset of surgical anesthesia is necessary. Ropivacaine should be administered in incremental doses.
    For minor nerve block anesthesia and infiltration anesthesia.
    Regional dosage for field block
    Adults

    1—40 ml of a 0.5% solution (5—200 mg) administered in incremental doses.

    For lumbar epidural anesthesia.
    Lumbar epidural dosage
    Adults

    15—30 ml of a 0.5% solution (75—150 mg), 15—25 ml of a 0.75% solution (113—188 mg), or 15—20 ml of a 1% solution (150—200 mg) administered in incremental doses. Long term (continuous) epidural infusion of ropivacaine was evaluated in 11 patients undergoing hip or knee surgery. Patients received an epidural infusion of ropivacaine 2 mg/ml at a rate of 6 ml/hour. The infusion rate was adjusted and ranged from 7—9 ml/ hour (14—18 mg) for up to 72 hours (range of 64—72 hours). The total amount of ropivacaine received during the study ranged between 690 and 1559 mg. Stable sensory block was achieved with minimal motor block.

    For caudal anesthesia†.
    Epidural dosage
    Children

    1 ml/kg (2.5 mg/kg) of 0.25% ropivacaine was similar to 0.25% bupivacaine (1 ml/kg or 2.5 mg/kg) in motor and sensory effects as well as quality and duration of postoperative pain relief.

    For peripheral nerve block, brachial plexus block.
    NOTE:  A higher frequency of adverse events from a local anesthetic may be associated with supraclavicular brachial plexus blocks. Administration of the local anesthetic for a major peripheral nerve block may lead to a high concentration of the drug in a highly vascularized area (see Administration).
    Regional dosage for major nerve block anesthesia
    Adults

    35—50 ml of a 0.5% solution (175—250 mg) or 10—40 ml of a 0.75% solution (75—300 mg) administered in incremental doses.

    For thoracic epidural anesthesia.
    Thoracic epidural dosage
    Adults

    5—15 ml of a 0.5% solution (25—75 mg) or 5—15 ml of a 0.75% solution (38—113 mg) administered in incremental doses.

    For obstetric anesthesia or Caesarean section anesthesia.
    Lumbar epidural infusion dosage
    Adults

    10—20 ml of a 0.2% solution (20—40 mg) initially, then 6—14 ml/hour of a 0.2% solution (12—28 mg/hour) as a continuous epidural infusion. Alternatively, 10—15 ml/hour of a 0.2% solution (20—30 mg/hour) administered in incremental doses.

    Lumbar epidural dosage
    Adults

    1—100 ml of a 0.2% solution (2—200 mg) or 1—40 ml of a 0.5% solution (5—200 mg) administered in incremental doses.

    Epidural dosage (Caesarean anesthesia)
    Adults

    20—30 ml of a 0.5% solution (100—150 mg) or 15—20 ml of a 0.75% solution (113—150 mg) in incremental doses.

    For postoperative treatment of severe pain.
    Lumbar epidural dosage
    Adults

    6—14 ml/hour of a 0.2% solution (12—28 mg/hour) as a continuous epidural infusion can provide analgesia with slight motor block. If regional anesthesia was not used intraoperatively, then an initial epidural block with 5—7 ml of a 0.2% solution epidurally may be given with a cumulative dose up to 770 mg over 24 hours (intraoperative block plus postoperative infusion). Continuous epidural infusions at rates up to 28 mg/hour for 72 hours (2016 mg plus surgical dose of approximately 100—150 mg as top-up) have been well tolerated. Administration of ropivacaine through this technique may reduce the need for opioids.

    Thoracic epidural dosage
    Adults

    6—14 ml/hour of a 0.2% solution (12—28 mg/hour) as a continuous epidural infusion for up to 72 hours.

    Regional dosage for minor nerve block
    Adults

    1—100 ml of a 0.2% solution (2—200 mg) or 1—40 ml of a 0.5% solution (5—200 mg) in incremental doses.

    For ophthalmic anesthesia†, specifically, peribulbar anesthesia and retrobulbar anesthesia.
    NOTE: Although the package labeling advises against this use of ropivacaine (see Contraindications/Precautions), ropivacaine has been studied for retrobulbar and peribulbar nerve block.
    Retrobulbar and Peribulbar dosage
    Adults

    Ropivacaine 0.2% was compared with lidocaine 1% in patients receiving peribulbar/retrobulbar anesthetic blocks. It was found that ropivacaine provided analgesia comparable to lidocaine for ocular surgical analgesia. Supplementary anesthesia was similar in both groups. Ropivacaine produced significantly less motor blockade at the end of treatment compared with lidocaine. Two hours after surgery, significantly more ropivacaine patients had impaired eye movements that required patching than with the lidocaine group.

    †Indicates off-label use

    MAXIMUM DOSAGE

    The dose of local anesthetics differs with the anesthetic procedure; the area to be anesthetized; the vascularity of the tissues; the number of neuronal segments to be blocked; the intensity of the block; the degree of muscle relaxation required; the duration of anesthesia desired; individual tolerance; and the physical condition of the patient.

    Adults

    The maximum dosage is dependent on route of administration and indication for therapy.

    Elderly

    The maximum dosage is dependent on route of administration and indication for therapy.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established; 2.5 mg/kg using a 0.25% solution has been used for caudal anesthesia.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Ropivacaine is extensively metabolized by the liver. Lower doses of ropivacaine may be required in patients with hepatic dysfunction due to prolonged effects and systemic accumulation. Specific dosage guidelines are not available.

    Renal Impairment

    The clearance of ropivacaine may be reduced. However specific guidelines for dosage adjustments in renal impairment are not available.

    ADMINISTRATION

    Injectable Administration

    Consult specialized references for specific procedures and administration techniques.
    Local anesthetics should only be administered by clinicians who are well versed in the diagnosis and management of dose-related toxicity and other acute emergencies that may arise from the block to be employed. Delay in proper management of dose-related toxicity, underventilation from any cause, or altered sensitivity may lead to the development of acidosis, cardiac arrest and, possibly, death.
    Carefully and constantly monitor cardiovascular and respiratory vital signs and the patient's state of consciousness after each injection and during continuous infusion. Resuscitative equipment and drugs used in the management of adverse reactions should be immediately available while administering local anesthetics.
    Administer by infiltration or peripheral block techniques. Avoid intravascular administration or subarachnoid injection. Aspirate for blood or cerebrospinal fluid before EACH injection. A negative aspiration does not ensure against an intravascular or subarachnoid injection but is a measure to help reduce the risk. Before receipt of a major block, determine the correct dose for your patient (see Dosage), take all necessary precautions to avoid intravascular administration, establish an intravenous line, and optimize the patient's general condition status.
    Ropivacaine solubility is limited at pH above 6. Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Do not administer solutions that are discolored or that have particulate matter.

    Other Injectable Administration

    Peripheral block
    Inject slowly and with frequent aspirations to prevent intravascular injection.
     
    Epidural administration
    This route of administration should only be used by specially trained healthcare professionals. Specialized references should be consulted for specific procedures and administration techniques.
    May be given as intermittent bolus, continuous infusion, or as patient-controlled epidural analgesia.
    Placement of the epidural catheter and administration should be at a site near the dermatomes covering the field of pain to decrease dose requirements and increase specificity.
    A test dose of 3—5 ml of a short acting amide anesthetic (e.g., lidocaine with epinephrine) is recommended to detect unintentional intrathecal administration. This will be manifested within a few minutes by signs of subarachnoid block (e.g., decreased sensation of the buttocks, paresis of the legs or absence of knee jerk reflex).
     
    Epidural injection:
    Injections containing preservatives should not be used for epidural injections.
    Discard any partially used injections that do not contain preservatives.
    After ensuring proper placement of the needle or catheter, inject appropriate dose in 3—5 ml increments into the epidural space. Inject doses slowly with frequent aspirations. Time should be taken in between doses to evaluate for toxic manifestations of inadvertent intravascular or intrathecal injection.
     
    Epidural infusion:
    A controlled-infusion device must be used. For highly concentrated injections, an implantable controlled-microinfusion device is used. Patients should be monitored for several days following implantation of the device.
    Injections containing preservatives should not be used for epidural infusion.
    Discard any partially used injections that do not contain preservatives.
    Preservative-free NS injection is recommended for dilution.
     
    Implantable controlled epidural infusion device:
    Filling of the infusion device reservoir should only be done by fully trained and qualified healthcare professionals. Strict aseptic technique must be used. Withdraw dose from the ampule through a 5-µm (or smaller pore diameter) microfilter to avoid contamination with glass or other particles. Remove filter needle and replace with a clean needle prior to injecting dosage into the reservoir. Ensure proper placement of the needle when filling the reservoir to avoid accidental overdosage.
    To avoid exacerbation of severe pain and/or reflux of CSF into the reservoir, depletion of the reservoir should be avoided.

    STORAGE

    Naropin:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Store at controlled room temperature (between 68 and 77 degrees F)
    Ropivacaine:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Requires a specialized care setting, requires an experienced clinician

    Ropivacaine use requires an experienced clinician who is well versed in the diagnosis and management of dose-related toxicity and other acute emergencies that might arise from ropivacaine exposure. Ropivacaine use also requires a specialized care setting; use ropivacaine only if the following are immediately available: oxygen, other resuscitative drugs, cardiopulmonary resuscitative equipment, and the personnel resources needed for proper management of toxic reactions and related emergencies. Delay in proper management of dose-related toxicity, underventilation from any cause, and/or altered sensitivity may lead to the development of acidosis, cardiac arrest, and, possibly, death.

    Intraarterial administration, intrathecal administration, intravenous administration

    Avoid intravenous administration, intraarterial administration, or intrathecal administration of ropivacaine. Do not perform regional intravenous anesthesia (Bier block) with ropivacaine due to a lack of clinical experience and the risk of attaining toxic blood concentrations of ropivacaine. Unintended intravascular or intrathecal injection may be associated with systemic toxicities, including central nervous system or cardiorespiratory depression and coma, ultimately progressing to respiratory arrest. Aspirate for blood or cerebrospinal fluid (when applicable) before injecting ropivacaine, both before the initial injection and with all subsequent doses, to avoid inadvertent intravascular or intrathecal administration. The absence of blood or cerebrospinal fluid does not ensure against intravascular or intrathecal injection. Administer an initial test dose before epidural administration. When clinical conditions permit, consider employing local anesthetic solutions which contain epinephrine for the test dose because circulatory changes compatible with epinephrine may also serve as a warning sign of unintended intravascular injection. Monitor the patient for central nervous system and cardiovascular toxicity, as well as signs of inadvertent intrathecal administration (e.g., decreased sensation of the buttocks, paresis of the legs, absent knee jerk) for an appropriate amount of time before the full dose is given.

    Head and neck anesthesia

    Small doses of ropivacaine used for local head and neck anesthesia may produce systemic toxicity similar to that seen with unintentional intravascular injections of larger doses. These reactions may be due to intraarterial injection of the local anesthetic with retrograde flow to the cerebral circulation. Monitor circulation and respiration constantly; resuscitative medications and equipment and appropriate supportive personnel should be immediately available.

    Ocular surgery

    The use of ropivacaine in retrobulbar blocks for ocular surgery has not been studied. Until appropriate experience is gained, ropivacaine use for such surgery is not recommended.

    Spinal anesthesia

    Do not use ropivacaine for spinal anesthesia due to insufficient data to support such use.

    AV block, hypotension, hypovolemia

    Use local anesthetics with caution in patients with hypotension, hypovolemia, or AV block. Patients in poor general condition due to partial or complete heart conduction block require special attention although regional anesthesia is frequently indicated in these patients. To reduce the risk of potentially serious adverse reactions, attempt to optimize the patient's condition before major blocks are performed, and adjust the dosage accordingly.

    Amide local anesthetic hypersensitivity

    Ropivacaine is contraindicated in patients with a known ropivacaine hypersensitivity or amide local anesthetic hypersensitivity.

    Hepatic disease

    Because amide-type local anesthetics are metabolized by the liver, use ropivacaine, especially repeat doses, cautiously in patients with hepatic disease. Patients with severe hepatic disease, because of their inability to metabolize local anesthetics normally, are at a greater risk of developing toxic plasma concentrations. Patients in poor general condition due to advanced liver disease require special attention although regional anesthesia is frequently indicated in these patients. To reduce the risk of potentially serious adverse reactions, attempt to optimize the patient's condition before major blocks are performed, and adjust the dosage accordingly.

    Renal failure, renal impairment

    Ropivacaine and its metabolites are known to be excreted by the kidney, and the risk of toxic reactions to ropivacaine may be greater in patients with renal impairment. Patients in poor general condition due to severe renal dysfunction or renal failure require special attention although regional anesthesia is frequently indicated in these patients. To reduce the risk of potentially serious adverse reactions, attempt to optimize the patient's condition before major blocks are performed, and adjust the dosage accordingly.

    Continuous intraarticular infusion administration

    Continuous intraarticular infusion administration of local anesthetics after arthroscopic and other surgical procedures is an unapproved use, and there have been postmarketing reports of chondrolysis in patients receiving such infusions. Patients who experienced chondrolysis have required additional diagnostic and therapeutic procedures, and some required arthroplasty or shoulder replacement.

    Malignant hyperthermia

    Many drugs used during anesthesia are considered triggering agents for familial malignant hyperthermia. Although it is unknown whether amide-type local anesthetics trigger this reaction, a standard protocol for management should be available when ropivacaine is administered. Early unexplained tachycardia, tachypnea, labile blood pressure, and metabolic acidosis may precede temperature elevation. Successful outcome is dependent on early diagnosis, prompt discontinuance of the suspected trigger(s), and prompt institution of treatment (e.g., oxygen, supportive measures, dantrolene).

    Geriatric

    Geriatric patients are more likely to have decreased hepatic, renal, or cardiac function, as well as concomitant disease. Therefore, take care in dose selection, starting at the low end of the dosage range, and it may be useful to monitor renal function. Patients in poor general condition due to aging require special attention although regional anesthesia is frequently indicated in these patients. To reduce the risk of potentially serious adverse reactions, attempt to optimize the patient's condition before major blocks are performed, and adjust the dosage accordingly.

    Cardiac disease, G6PD deficiency, infants, methemoglobinemia, neonates, pulmonary disease

    Closely monitor patients with glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency), congenital or idiopathic methemoglobinemia, cardiac or pulmonary compromise (cardiac disease or pulmonary disease), neonates and infants younger than 6 months, and those with concurrent exposure to oxidizing agents or their metabolites for signs and symptoms of methemoglobinemia. Methemoglobinemia is characterized by cyanotic skin discoloration and abnormal coloration of the blood, presenting immediately or within hours of local anesthetic exposure. Discontinue ropivacaine and any other oxidizing agents immediately and initiate supportive care (e.g., oxygen, hydration) if necessary to avoid serious central nervous system and cardiovascular effects. Severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.[52330]

    Labor, obstetric delivery, paracervical nerve block, pregnancy, pudendal nerve block

    Use ropivacaine during pregnancy only if the benefits outweigh the risks. Do not use ropivacaine for the production of obstetrical paracervical nerve block anesthesia due to insufficient data to support such use. Unintended fetal intracranial injection of local anesthetics after intended paracervical or pudendal nerve block for obstetrical anesthesia may cause neonatal depression and seizures. Supportive measures and forced urinary excretion of the local anesthetic have been used successfully to manage this complication.[43383] There are no adequate and well-controlled studies in pregnant women of the effects of ropivacaine on the developing fetus. Teratogenicity studies in rats and rabbits did not show evidence of any adverse effects on organogenesis or early fetal development in rats or rabbits given subcutaneous ropivacaine. The highest doses of 13 mg/kg/day (rabbits) and 26 mg/kg/day (rats) are approximately one-third of the maximum recommended human dose (epidural, 770 mg/24 hours) based on a mg/m2 basis. There were no treatment-related effects on late fetal development, parturition, lactation, neonatal viability, or growth of the offspring in 2 perinatal and postnatal studies in rats, at doses equivalent to the maximum recommended human dose based on body surface area. In another study at 23 mg/kg, an increased pup loss was seen during the first 3 days postpartum, which was considered secondary to impaired maternal care due to maternal toxicity. Local anesthetics rapidly cross the placenta, and when used for epidural, caudal, or pudendal block anesthesia, can cause varying degrees of maternal, fetal, and neonatal toxicity. The incidence and degree of toxicity depend upon the procedure performed, the type and amount of drug used, and the technique of drug administration. Adverse reactions in the pregnant woman, fetus, and neonate involve alterations of the central nervous system, peripheral vascular tone, and cardiac function. Spontaneous vertex delivery occurred more frequently in patients receiving ropivacaine than in those receiving bupivacaine. It is extremely important to avoid aortocaval compression by the gravid uterus during administration of regional block to a pregnant patient. To do this, maintain the patient in the left lateral decubitus position, or a blanket roll or sandbag may be placed beneath the right hip and gravid uterus displaced to the left. Maternal hypotension has resulted from regional anesthesia. Local anesthetics produce vasodilation by blocking sympathetic nerves. During treatment of systemic toxicity, maternal hypotension, or fetal bradycardia after regional block, maintain the pregnant patient in the left lateral decubitus position if possible, or manually displace the uterus off the great vessels. Elevating the patient's legs will also help prevent decreases in blood pressure. Monitor the fetal heart rate continuously, and electronic fetal monitoring is highly advisable. Epidural, spinal, or pudendal nerve block may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts. Epidural anesthesia may prolong the second stage of labor by removing the reflex urge to bear down or interfering with motor function. The use of obstetrical anesthesia may increase the need for forceps assistance. The use of some local anesthetic drug products during labor and obstetric delivery may be followed by diminished muscle strength and tone in a neonate for the first day or 2 of life. Placental transfer of local anesthetics is dependent upon the degree of plasma protein binding, ionization, and lipid solubility of each agent. Fetal to maternal ratios of local anesthetics appear to be inversely related to the degree of plasma protein binding since only free, unbound drug is available for placental transfer.  

    Breast-feeding

    Use caution when administering ropivacaine to a breast-feeding woman; some local anesthetics are excreted in human milk. The excretion of ropivacaine or its metabolites in human milk has not been studied. Based on the milk/plasma concentration ratio in rats, the estimated daily dose to a pup will be about 4% of the dose given to the mother. Assuming that the milk/plasma concentration in humans is of the same order, the total ropivacaine dose to which the infant is exposed by breast-feeding is far lower than by exposure in utero in pregnant women at term. Due to poor oral absorption of local anesthetics, the potential for adverse effects in the nursing infant is low. In general, use of ropivacaine during surgery or other procedures allows breast-feeding of the healthy term infant to be permissible as soon as the mother is awake and alert. A prospective cohort study comparing women who received no analgesia (n = 63) to women who received continuous epidural fentanyl and either bupivacaine 0.05 to 0.1% (n = 39) or ropivacaine (n = 13) during labor and delivery found no differences between the groups in breast-feeding effectiveness or infant neurobehavioral status at 8 to 12 hours postpartum. Although ropivacaine has not been evaluated by the American Academy of Pediatrics (AAP), previous AAP recommendations considered lidocaine to be usually compatible with breast-feeding.

    ADVERSE REACTIONS

    Severe

    bradycardia / Rapid / 5.0-20.0
    oliguria / Early / 1.0-5.0
    ventricular tachycardia / Early / 1.0-5.0
    seizures / Delayed / 0-1.0
    myocardial infarction / Delayed / 0-1.0
    atrial fibrillation / Early / 0-1.0
    bronchospasm / Rapid / 0-1.0
    thrombosis / Delayed / 0-1.0
    pulmonary embolism / Delayed / 0-1.0
    muscle paralysis / Delayed / Incidence not known
    anaphylactoid reactions / Rapid / Incidence not known
    laryngeal edema / Rapid / Incidence not known
    respiratory arrest / Rapid / Incidence not known
    coma / Early / Incidence not known
    ventricular fibrillation / Early / Incidence not known
    visual impairment / Early / Incidence not known
    cardiac arrest / Early / Incidence not known
    AV block / Early / Incidence not known
    chondrolysis / Delayed / Incidence not known
    malignant hyperthermia / Rapid / Incidence not known
    methemoglobinemia / Early / Incidence not known

    Moderate

    hypotension / Rapid / 32.0-54.0
    fetal bradycardia / Delayed / 12.1-12.1
    jaundice / Delayed / 7.7-7.7
    anemia / Delayed / 6.0-6.0
    urinary retention / Early / 1.0-5.0
    hypertension / Early / 1.0-5.0
    chest pain (unspecified) / Early / 1.0-5.0
    sinus tachycardia / Rapid / 1.0-5.0
    dyspnea / Early / 1.0-5.0
    hypokalemia / Delayed / 1.0-5.0
    tachypnea / Early / 2.0-2.0
    fetal distress / Delayed / 1.7-1.7
    hypoglycemia / Early / 1.3-1.3
    fecal incontinence / Early / 0-1.0
    urinary incontinence / Early / 0-1.0
    blurred vision / Early / 0-1.0
    confusion / Early / 0-1.0
    orthostatic hypotension / Delayed / 0-1.0
    phlebitis / Rapid / 0-1.0
    hypomagnesemia / Delayed / 0-1.0
    meningitis / Delayed / Incidence not known
    edema / Delayed / Incidence not known
    erythema / Early / Incidence not known
    dyskinesia / Delayed / Incidence not known
    hypotonia / Delayed / Incidence not known
    respiratory depression / Rapid / Incidence not known
    hallucinations / Early / Incidence not known
    depression / Delayed / Incidence not known
    amnesia / Delayed / Incidence not known
    paresis / Delayed / Incidence not known
    angina / Early / Incidence not known
    premature ventricular contractions (PVCs) / Early / Incidence not known
    palpitations / Early / Incidence not known
    fetal acidosis / Delayed / Incidence not known
    decreased uterine contractility / Early / Incidence not known

    Mild

    nausea / Early / 13.0-25.0
    back pain / Delayed / 4.0-17.0
    vomiting / Early / 7.0-12.0
    fever / Early / 2.0-9.0
    headache / Early / 4.0-8.0
    paresthesias / Delayed / 2.0-6.0
    pruritus / Rapid / 1.0-5.0
    chills / Rapid / 2.0-3.0
    dizziness / Early / 2.5-2.5
    hypoesthesia / Delayed / 1.6-1.6
    infection / Delayed / 1.6-1.6
    anxiety / Delayed / 1.3-1.3
    rhinitis / Early / 1.1-1.1
    tenesmus / Delayed / 0-1.0
    urticaria / Rapid / 0-1.0
    hypothermia / Delayed / 0-1.0
    tremor / Early / 0-1.0
    drowsiness / Early / 0-1.0
    asthenia / Delayed / 0-1.0
    malaise / Early / 0-1.0
    tinnitus / Delayed / 0-1.0
    syncope / Early / 0-1.0
    injection site reaction / Rapid / 0-1.0
    myalgia / Early / 0-1.0
    cough / Delayed / 0-1.0
    weakness / Early / Incidence not known
    libido decrease / Delayed / Incidence not known
    sneezing / Early / Incidence not known
    hyperhidrosis / Delayed / Incidence not known
    agitation / Early / Incidence not known
    emotional lability / Early / Incidence not known
    restlessness / Early / Incidence not known
    nightmares / Early / Incidence not known
    insomnia / Early / Incidence not known
    vertigo / Early / Incidence not known
    diplopia / Early / Incidence not known

    DRUG INTERACTIONS

    Acebutolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Acetaminophen: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Caffeine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Chlorpheniramine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Codeine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Acetaminophen; Dextromethorphan: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Diphenhydramine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Guaifenesin; Phenylephrine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Hydrocodone: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Acetaminophen; Oxycodone: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Pentazocine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Acetaminophen; Propoxyphene: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Acetaminophen; Pseudoephedrine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Alfentanil: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Ambenonium Chloride: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine.
    Aminosalicylate sodium, Aminosalicylic acid: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as aminosalicylic acid, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Amyl Nitrite: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Aprepitant, Fosaprepitant: (Major) Use caution if ropivacaine and aprepitant, fosaprepitant are used concurrently and monitor for an increase in ropivacaine-related adverse effects for several days after administration of a multi-day aprepitant regimen. Ropivacaine is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of ropivacaine. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
    Articaine; Epinephrine: (Moderate) Use articaine and ropivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Aspirin, ASA; Oxycodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Atazanavir: (Moderate) The plasma concentrations of ropivacaine may be elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects, such as hypotension, bradycardia or GI effects, is recommended during coadministration. Atazanavir is a CYP3A4 inhibitor, while ropivacaine is a CYP3A4 substrate.
    Atazanavir; Cobicistat: (Moderate) The plasma concentrations of ropivacaine may be elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects, such as hypotension, bradycardia or GI effects, is recommended during coadministration. Atazanavir is a CYP3A4 inhibitor, while ropivacaine is a CYP3A4 substrate. (Moderate) The plasma concentrations of ropivacaine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hypotension, bradycardia or GI effects, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while ropivacaine is a CYP3A4 substrate.
    Atenolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Atenolol; Chlorthalidone: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Atracurium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Atropine; Edrophonium: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine.
    Belladonna Alkaloids; Ergotamine; Phenobarbital: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as phenobarbital, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Belladonna; Opium: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Bendroflumethiazide; Nadolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Benzalkonium Chloride; Benzocaine: (Moderate) Use ropivacaine and benzocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Benzhydrocodone; Acetaminophen: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Benzocaine: (Moderate) Use ropivacaine and benzocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Benzocaine; Butamben; Tetracaine: (Moderate) Use ropivacaine and benzocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Benzonatate: (Major) Caution is advised if amide local anesthetics are used concurrently with benzonatate. The toxic effects of local anesthetics are additive.
    Beta-adrenergic blockers: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Betaxolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Bisoprolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Boceprevir: (Moderate) Close clinical monitoring is advised when administering ropivacaine with boceprevir due to an increased potential for ropivacaine-related adverse events. If ropivacaine dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of ropivacaine. Ropivacaine is partially metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated ropivacaine plasma concentrations.
    Brimonidine; Timolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Bupivacaine Liposomal: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use other formulations of bupivacaine and ropivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Bupivacaine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use other formulations of bupivacaine and ropivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Bupivacaine; Lidocaine: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use other formulations of bupivacaine and ropivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Use lidocaine and ropivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Bupivacaine; Meloxicam: (Major) Avoid use of other local anesthetics for 96 hours after liposomal bupivacaine administration. Use other formulations of bupivacaine and ropivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Butalbital; Acetaminophen: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Butalbital; Acetaminophen; Caffeine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Carteolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Carvedilol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Chloroprocaine: (Moderate) Use ropivacaine and chloroprocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Chloroquine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as chloroquine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Chlorpheniramine; Codeine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Chlorpheniramine; Hydrocodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Cimetidine: (Major) Known inhibitors of cytochrome P450 1A2, such as cimetidine, may increase the systemic levels of ropivacaine and increase the risk of toxicity when given concurrently.
    Ciprofloxacin: (Moderate) Ropivacaine is metabolized to a 3-OH metabolite primarily by CYP1A2 and to a lesser extent to the pipecoloxylidide (PPX) metabolite by CYP3A4. In a double-blind study, ciprofloxacin reduced the mean plasma clearance of ropivacaine by 31% by inhibiting CYP1A2 and increased the formation of PPX by redirecting metabolism to CYP3A4.
    Cisatracurium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Cobicistat: (Moderate) The plasma concentrations of ropivacaine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hypotension, bradycardia or GI effects, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while ropivacaine is a CYP3A4 substrate.
    Codeine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Codeine; Guaifenesin: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Codeine; Guaifenesin; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Codeine; Phenylephrine; Promethazine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Codeine; Promethazine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Cyclophosphamide: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as cyclophosphamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Dapsone: (Moderate) Coadministration of dapsone with ropivacaine may increase the risk of developing methemoglobinemia. Advise patients to discontinue treatment and seek immediate medical attention with any signs or symptoms of methemoglobinemia.
    Daratumumab; Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
    Darunavir: (Moderate) The plasma concentrations of ropivacaine may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as hypotension, bradycardia or GI effects, is recommended during coadministration. Darunavir is a CYP3A4 inhibitor, while ropivacaine is a CYP3A4 substrate.
    Darunavir; Cobicistat: (Moderate) The plasma concentrations of ropivacaine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hypotension, bradycardia or GI effects, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while ropivacaine is a CYP3A4 substrate. (Moderate) The plasma concentrations of ropivacaine may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as hypotension, bradycardia or GI effects, is recommended during coadministration. Darunavir is a CYP3A4 inhibitor, while ropivacaine is a CYP3A4 substrate.
    Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) The plasma concentrations of ropivacaine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hypotension, bradycardia or GI effects, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while ropivacaine is a CYP3A4 substrate. (Moderate) The plasma concentrations of ropivacaine may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as hypotension, bradycardia or GI effects, is recommended during coadministration. Darunavir is a CYP3A4 inhibitor, while ropivacaine is a CYP3A4 substrate.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Donepezil: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine.
    Donepezil; Memantine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine.
    Dorzolamide; Timolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Doxacurium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Edrophonium: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine.
    Elbasvir; Grazoprevir: (Moderate) Administering ropivacaine with elbasvir; grazoprevir may result in elevated ropivacaine plasma concentrations. Ropivacaine is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) The plasma concentrations of ropivacaine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hypotension, bradycardia or GI effects, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while ropivacaine is a CYP3A4 substrate.
    Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) The plasma concentrations of ropivacaine may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as hypotension, bradycardia or GI effects, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while ropivacaine is a CYP3A4 substrate.
    Erythromycin; Sulfisoxazole: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Esmolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Fentanyl: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for epidural analgesia or additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Flutamide: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Fluvoxamine: (Major) Ropivacaine is metabolized primarily by cytochrome P450 (CYP) isoenzyme 1A2. Agents that are known inhibitors of CYP1A2, such as fluvoxamine, may result in increased systemic levels of ropivacaine when given concurrently, resulting in toxicity. In vivo, the plasma clearance of ropivacaine was reduced by 70% and the half-life doubled during concurrent administration of fluvoxamine.
    Fosphenytoin: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as fosphenytoin, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Galantamine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine.
    Guaifenesin; Hydrocodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Homatropine; Hydrocodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Hyaluronidase, Recombinant; Immune Globulin: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
    Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
    Hydralazine; Isosorbide Dinitrate, ISDN: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Hydrocodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Hydrocodone; Ibuprofen: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Hydrocodone; Phenylephrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Hydrocodone; Pseudoephedrine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Hydromorphone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Hydroxyurea: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as hydroxyurea, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Ibuprofen; Oxycodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with ropivacaine, a CYP3A substrate, as ropivacaine toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
    Ifosfamide: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as ifosfamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Isocarboxazid: (Major) Patients receiving local anesthetics may have an increased risk of hypotension. Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors (e.g., epinephrine) are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
    Isosorbide Dinitrate, ISDN: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Isosorbide Mononitrate: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Ketoconazole: (Moderate) Concurrent administration of ketoconazole and ropivacaine may result in elevated ropivacaine serum concentration; thereby increasing the risk for drug toxicity. The metabolism of ropivacaine to 3-hydroxyropivacaine is dependent on CYP1A2, and the metabolism of ropivacaine to (S)-2',6'-pipecoloxylidide is dependent on CYP3A4. Ropivacaine is metabolized to a lesser extent by cytochrome CYP3A4. Without the presence of an enzyme inducer or inhibitor, the fraction of a ropivacaine dose that is converted to (S)-2',6'-pipecoloxylidide is 0.01 +/- 0.02 whereas 0.39 +/- 0.05 is converted to 3-hydroxyropivacaine. In the presence of the CYP3A4 inhibitor, ketoconazole, the disposition of ketoconazole was all 3-hydroxyropivacaine (0.47 +/- 0.07). Concurrent administration of ketoconazole (100 mg twice daily for 2 days with ropivacaine infusion administered 1 hour after ketoconazole) caused a 15% reduction in in vivo ropivacaine plasma clearance. Plasma ropivacaine concentrations increased slightly.
    Labetalol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Levobetaxolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Levobunolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Levomethadyl: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Levorphanol: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Lidocaine: (Moderate) Use lidocaine and ropivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Lidocaine; Prilocaine: (Moderate) Use lidocaine and ropivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Use ropivacaine and prilocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Lumacaftor; Ivacaftor: (Minor) Lumacaftor; ivacaftor may reduce the efficacy of ropivacaine by increasing its clearance; if used together, monitor therapeutic response and adjust the ropivacaine dosage as needed to attain appropriate anesthesia. Ropivacaine is partially metabolized by CYP3A4. Lumacaftor is a strong CYP3A inducer.
    Lumacaftor; Ivacaftor: (Minor) Lumacaftor; ivacaftor may reduce the efficacy of ropivacaine by increasing its clearance; if used together, monitor therapeutic response and adjust the ropivacaine dosage as needed to attain appropriate anesthesia. Ropivacaine is partially metabolized by CYP3A4. Lumacaftor is a strong CYP3A inducer.
    Magnesium Salts: (Minor) Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as local anesthetics. Caution should be exercised when using these agents concurrently.
    Meperidine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Meperidine; Promethazine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Mepivacaine: (Moderate) Use mepivacaine and ropivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Mepivacaine; Levonordefrin: (Moderate) Use mepivacaine and ropivacaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Methadone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Metoclopramide: (Moderate) Coadministration of ropivacaine with metoclopramide may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other agents associated with methemoglobinemia. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Metoprolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Minocycline: (Moderate) Injectable minocycline contains magnesium sulfate heptahydrate. Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as local anesthetics. Caution should be exercised when using these agents concurrently.
    Mitotane: (Moderate) Use caution if mitotane and ropivacaine are used concomitantly, and monitor for decreased efficacy of ropivacaine and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer. Ropivacaine is a CYP3A4 substrate, although inhibition of this enzyme does not lead to clinically relevant changes in ropivacaine clearance; coadministration may theoretically result in decreased plasma concentrations of ropivacaine.
    Mivacurium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Monoamine oxidase inhibitors: (Major) Patients receiving local anesthetics may have an increased risk of hypotension. Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors (e.g., epinephrine) are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
    Morphine: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Morphine; Naltrexone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Nadolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Nebivolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Nebivolol; Valsartan: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Neostigmine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine.
    Neuromuscular blockers: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Nitrates: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Nitrofurantoin: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as nitrofurantoin, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Nitroglycerin: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as nitrates, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Obeticholic Acid: (Moderate) Obeticholic acid may increase the exposure to concomitant drugs that are CYP1A2 substrates, such as ropivacaine. Clinical monitoring for adverse effects, such as hypotension, bradycardia or GI effects, is recommended during coadministration.
    Oxycodone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Oxymorphone: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Pancuronium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Pazopanib: (Moderate) Pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and ropivacaine, a CYP3A4 substrate, may cause an increase in systemic concentrations of ropivacaine. Use caution when administering these drugs concomitantly.
    Peginterferon Alfa-2b: (Moderate) Monitor for adverse effects, such as hypotension, bradycardia or GI effects, associated with increased exposure to ropivacaine if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 inhibitor and ropivacaine is metabolized to a 3-OH metabolite primarily by CYP1A2 and to a lesser extent to the pipecoloxylidide (PPX) metabolite by CYP3A4.
    Penbutolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Penicillin G Benzathine; Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with other local anesthetics, such as ropivacaine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other local anesthetic. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with other local anesthetics, such as ropivacaine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other local anesthetic. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Pertuzumab; Trastuzumab; Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
    Phenelzine: (Major) Patients receiving local anesthetics may have an increased risk of hypotension. Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors (e.g., epinephrine) are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
    Phenobarbital: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as phenobarbital, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as phenobarbital, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Phenytoin: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as phenytoin, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Physostigmine: (Moderate) Local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used. Also, local anesthetics interfere with the release of acetylcholine.
    Pindolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Prilocaine: (Moderate) Use ropivacaine and prilocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Prilocaine; Epinephrine: (Moderate) Use ropivacaine and prilocaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Primaquine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as primaquine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Primidone: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as primidone, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Procarbazine: (Major) Patients taking procarbazine should not be given local anesthetics containing sympathomimetic vasoconstrictors; coadministration may invoke a severe hypertensive reaction. Procarbazine should be discontinued for at least 10 days prior to elective surgery.
    Propoxyphene: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic may allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Propranolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Pyrimethamine; Sulfadoxine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Quinine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as quinine, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Rapacuronium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Rasburicase: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as rasburicase, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Remifentanil: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Rituximab; Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
    Rocuronium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Rofecoxib: (Major) Ropivacaine is metabolized primarily by cytochrome P450 isoenzyme 1A2. Interactions are possible with other drug known to be inhibitors of CYP1A2, such as rofecoxib.
    Simeprevir: (Moderate) Simeprevir, a mild CYP1A2 inhibitor and a mild intestinal CYP3A4 inhibitor, may increase the side effects of ropivacaine, which is a CYP1A2 and CYP3A4 substrate. Monitor patients for adverse effects of ropivacaine, such as hypotension, CNS toxicity, and respiratory depression.
    Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Minor) Because of the CNS-depressant effects of magnesium sulfate, additive central-depressant effects can occur following concurrent administration with CNS depressants such as local anesthetics. Caution should be exercised when using these agents concurrently.
    Succinylcholine: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Sufentanil: (Moderate) The use of these drugs together must be approached with caution. Although commonly used together for additive analgesic effects, the patient must be monitored for respiratory depression, hypotension, and excessive sedation due to additive effects on the CNS and blood pressure. In rare instances, serious morbidity and mortality has occurred. Limit the use of opiate pain medications with local anesthetics to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. The use of the local anesthetic will allow for the use a lower initial dose of the opiate and then the doses can be titrated to proper clinical response. Educate patients about the risks and symptoms of respiratory depression and sedation.
    Sulfadiazine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Sulfasalazine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Sulfisoxazole: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Sulfonamides: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as sulfonamides, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Tacrine: (Major) Known inhibitors of cytochrome P450 CYP1A2, such as tacrine, may increase the systemic plasma concentrations of ropivacaine and increase the risk of toxicity when given concurrently. Also, local anesthetics can antagonize the effects of cholinesterase inhibitors by inhibiting neuronal transmission in skeletal muscle, especially if large doses of local anesthetics are used.
    Telaprevir: (Moderate) Close clinical monitoring is advised when administering ropivacaine with telaprevir due to an increased potential for ropivacaine-related adverse events. If ropivacaine dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of ropivacaine. Ropivacaine is partially metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated ropivacaine plasma concentrations.
    Tetracaine: (Moderate) Use ropivacaine and tetracaine together with caution. Monitor cardiovascular and respiratory vital signs, as well as the patient's state of consciousness if used concurrently due to potential for additive CNS and/or cardiovascular toxic effects. Manifestations of toxicity may include CNS excitation and/or depression, cardiac conduction depression, or peripheral vasodilation. Additionally, coadministration may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue local anesthetic use. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Theophylline, Aminophylline: (Minor) Agents that are also metabolized by cytochrome P450 1A2, such as aminophylline, may decrease the metabolism of ropivacaine through competitive inhibition. (Minor) Agents that are also metabolized by cytochrome P450 1A2, such as theophylline, may decrease the metabolism of ropivacaine through competitive inhibition.
    Thiabendazole: (Moderate) Thiabendazole is a potent CYP1A2 inhibitor. Ropivacaine is metabolized to a 3-OH metabolite primarily by CYP1A2 and to a lesser extent to the pipecoloxylidide (PPX) metabolite by CYP3A4. Other significant CYP1A2 inhibitors can reduce the mean plasma clearance of ropivacaine by inhibiting CYP1A2 and increase the formation of PPX by redirecting metabolism to CYP3A4. Use caution and monitor closely during times of coadministration.
    Timolol: (Moderate) Local anesthetics may cause additive hypotension in combination with antihypertensive agents.
    Tramadol; Acetaminophen: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as acetaminophen, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Tranylcypromine: (Major) Patients receiving local anesthetics may have an increased risk of hypotension. Combined hypotensive effects are possible with use of MAOIs and spinal anesthetics. When local anesthetics containing sympathomimetic vasoconstrictors (e.g., epinephrine) are coadministered with MAOIs, severe and prolonged hypertension may occur. MAOIs can increase the sensitivity to epinephrine by inhibiting epinephrine reuptake or metabolism. If concurrent therapy is necessary, carefully monitor the patient. Phenelzine and tranylcypromine are contraindicated for use for at least 10 days prior to elective surgery.
    Trastuzumab; Hyaluronidase: (Moderate) Hyaluronidase, when used in combination with local anesthetics, hastens the onset of analgesia and reduces the swelling caused by local infiltration; this interaction is beneficial and is the reason hyaluronidase is used adjunctively in local infiltrative anesthesia techniques. However, the wider spread of the local anesthetic solution may increase the systemic absorption of the local anesthetic, which shortens the duration of anesthetic action and tends to increase the potential risk for systemic side effects.
    Tubocurarine: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Valproic Acid, Divalproex Sodium: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as valproic acid, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
    Vecuronium: (Moderate) Concomitant use of neuromuscular blockers and local anesthetics may prolong neuromuscular blockade. The use of a peripheral nerve stimulator is strongly recommended to evaluate the level of neuromuscular blockade, to assess the need for additional doses of neuromuscular blocker, and to determine whether adjustments need to be made to the dose with subsequent administration.
    Viloxazine: (Moderate) Use caution when ropivacaine is coadministered with viloxazine. Concomitant use may lead to increased ropivacaine concentrations. Ropivacaine is a CYP1A2 substrate and viloxazine is a strong CYP1A2 inhibitor. Coadministration with another strong CYP1A2 inhibitor decreased the clearance of ropivacaine by 70%.
    Zileuton: (Major) Concomitant use of ropivacaine and zileuton may result in increased systemic concentrations of ropivacaine and subsequent toxicity. Ropivacaine is metabolized primarily by CYP1A2. Zileuton is a competitive inhibitor of CYP1A2.

    PREGNANCY AND LACTATION

    Pregnancy

    Use ropivacaine during pregnancy only if the benefits outweigh the risks. Do not use ropivacaine for the production of obstetrical paracervical nerve block anesthesia due to insufficient data to support such use. Unintended fetal intracranial injection of local anesthetics after intended paracervical or pudendal nerve block for obstetrical anesthesia may cause neonatal depression and seizures. Supportive measures and forced urinary excretion of the local anesthetic have been used successfully to manage this complication.[43383] There are no adequate and well-controlled studies in pregnant women of the effects of ropivacaine on the developing fetus. Teratogenicity studies in rats and rabbits did not show evidence of any adverse effects on organogenesis or early fetal development in rats or rabbits given subcutaneous ropivacaine. The highest doses of 13 mg/kg/day (rabbits) and 26 mg/kg/day (rats) are approximately one-third of the maximum recommended human dose (epidural, 770 mg/24 hours) based on a mg/m2 basis. There were no treatment-related effects on late fetal development, parturition, lactation, neonatal viability, or growth of the offspring in 2 perinatal and postnatal studies in rats, at doses equivalent to the maximum recommended human dose based on body surface area. In another study at 23 mg/kg, an increased pup loss was seen during the first 3 days postpartum, which was considered secondary to impaired maternal care due to maternal toxicity. Local anesthetics rapidly cross the placenta, and when used for epidural, caudal, or pudendal block anesthesia, can cause varying degrees of maternal, fetal, and neonatal toxicity. The incidence and degree of toxicity depend upon the procedure performed, the type and amount of drug used, and the technique of drug administration. Adverse reactions in the pregnant woman, fetus, and neonate involve alterations of the central nervous system, peripheral vascular tone, and cardiac function. Spontaneous vertex delivery occurred more frequently in patients receiving ropivacaine than in those receiving bupivacaine. It is extremely important to avoid aortocaval compression by the gravid uterus during administration of regional block to a pregnant patient. To do this, maintain the patient in the left lateral decubitus position, or a blanket roll or sandbag may be placed beneath the right hip and gravid uterus displaced to the left. Maternal hypotension has resulted from regional anesthesia. Local anesthetics produce vasodilation by blocking sympathetic nerves. During treatment of systemic toxicity, maternal hypotension, or fetal bradycardia after regional block, maintain the pregnant patient in the left lateral decubitus position if possible, or manually displace the uterus off the great vessels. Elevating the patient's legs will also help prevent decreases in blood pressure. Monitor the fetal heart rate continuously, and electronic fetal monitoring is highly advisable. Epidural, spinal, or pudendal nerve block may alter the forces of parturition through changes in uterine contractility or maternal expulsive efforts. Epidural anesthesia may prolong the second stage of labor by removing the reflex urge to bear down or interfering with motor function. The use of obstetrical anesthesia may increase the need for forceps assistance. The use of some local anesthetic drug products during labor and obstetric delivery may be followed by diminished muscle strength and tone in a neonate for the first day or 2 of life. Placental transfer of local anesthetics is dependent upon the degree of plasma protein binding, ionization, and lipid solubility of each agent. Fetal to maternal ratios of local anesthetics appear to be inversely related to the degree of plasma protein binding since only free, unbound drug is available for placental transfer.  

    MECHANISM OF ACTION

    Mechanism of Action: Ropivacaine works by interfering with sodium entry into nerve cell membranes. Like all local anesthetics, ropivacaine causes a reversible nerve-conduction blockade by decreasing nerve membrane permeability to sodium. This decreases the rate of membrane depolarization, thereby increasing the threshold for electrical excitability. The blockade affects all nerve fibers in the following sequence: autonomic, sensory, and motor, with effects diminishing in reverse order. Loss of nerve function clinically is as follows: pain, temperature, touch, proprioception, and skeletal muscle tone.Systemic absorption of local anesthetics can produce effects on the central nervous and cardiovascular systems. At blood concentrations achieved with therapeutic doses, changes in cardiac conduction, excitability, refractoriness, contractility, and peripheral vascular resistance have been reported. Toxic blood concentrations depress cardiac conduction and excitability, which may lead to AV block, ventricular arrhythmia, and cardiac arrest, sometimes resulting in fatalities. In addition, myocardial contractility is depressed and peripheral vasodilatation occurs, leading to decreased cardiac output and arterial blood pressure. Following systemic absorption, local anesthetics can produce central nervous system stimulation, depression, or both. CNS stimulation is usually manifested as restlessness, tremors, and shivering progressing to convulsions, followed by depression and coma, progressing ultimately to respiratory arrest. However, local anesthetics have a primary depressant effect on the medulla and higher centers. The depressed stage may occur without the prior excitatory stage. Animal studies demonstrated that the cardiac toxicity of ropivacaine is less than bupivacaine, although both agents were more toxic than lidocaine. Ropivacaine caused significantly less depression of cardiac contractility (less QRS widening) than bupivacaine. Both caused evidence of depression of cardiac contractility, but there were no changes in cardiac output. In human studies, similar CNS symptoms were seen with both ropivacaine and bupivacaine.

    PHARMACOKINETICS

    Ropivacaine is given parenterally either as an epidural infusion or a regional nerve block. (NOTE: INTRAVENOUS ADMINISTRATION IS TO BE AVOIDED.) Absorption is dependent on the total dose and concentration of drug administered, the route of administration, the patient's hemodynamic/circulatory condition and the vascularity of the administration site. Unlike other local anesthetics, epinephrine has no major effect on either the time of onset or the duration of action of ropivacaine. Therefore, the addition of epinephrine has no effect on limiting systemic absorption.
     
    Ropivacaine is distributed to all tissues and highly protein bound to alpha-1 acid glycoprotein. It is extensively metabolized by the liver and is excreted renally with 1% of the dose excreted unchanged.
     
    Affected cytochrome P450 isoenzymes and drug transporters:  CYP1A2, CYP3A4
    The metabolism of ropivacaine to 3-hydroxyropivacaine is dependent on CYP1A2, and the metabolism of ropivacaine to (S)-2',6'-pipecoloxylidide is dependent on CYP3A4. CYP3A4 is involved to a lesser extent, and inhibition of this enzyme does not lead to clinically relevant changes in ropivacaine clearance.

    Other Route(s)

    Epidural route
    After epidural injection, ropivacaine shows a biphasic absorption, with an initial rapid phase half-life (mean of 14 +/- 7 minutes) and a slower phase (4.2 +/- 0.9 minutes). After administration of ropivacaine the onset of action occurs at 10—25 minutes with a duration of 2—4 hours. The terminal half life of ropivacaine is 4.2 +/- 1.0 hours after epidural administration. The terminal half-life is longer after epidural administration than after intravenous administration because of this slow absorption.
     
    Nerve block 
    After administration of ropivacaine the onset of action occurs at 15—30 minutes for major nerve block with a duration of 5—8 hours.
     
    Field block 
    After administration of ropivacaine the onset of action occurs at 1—15 minutes for field block with a duration of 2—6 hours.
     
    Intravascular route
    The terminal half life of ropivacaine is 1.8 +/- 0.7 hours after intravascular administration.