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  • CLASSES

    Injectable Bisphosphonates
    Oral Bisphosphonates

    DEA CLASS

    Rx

    DESCRIPTION

    Potent oral and parenteral third-generation bisphosphonate
    Primarily used for treatment and prevention of postmenopausal osteoporosis; increases bone mineral density and reduces vertebral fracture risk; consider if spine-specific osteoporosis therapy needed
    Used off-label for hypercalcemia of malignancy and for reduction of skeletal events in patients with breast cancer and bone metastases

    COMMON BRAND NAMES

    Boniva

    HOW SUPPLIED

    Boniva/Ibandronate Sodium Intravenous Inj Sol: 3mg, 3mL
    Boniva/Ibandronate Sodium Oral Tab: 150mg

    DOSAGE & INDICATIONS

    For the treatment of osteoporosis.
    Once monthly oral regimen for postmenopausal osteoporosis.
    Oral dosage
    Adult postmenopausal females

    150 mg PO once monthly on the same date each month. Supplement with calcium and vitamin D if dietary intake is inadequate. Once per month dosing has similar clinical effects when compared to the previously available 2.5 mg/day dosing regimen.[27859] The optimal treatment duration has not been determined; reevaluate treatment on a periodic basis. For those patients at low risk for fracture, consider stopping ibandronate after 3 to 5 years. After discontinuation of therapy, continue to periodically reassess fracture risk. Bisphosphonates are a first-line therapy for the treatment of osteoporosis in postmenopausal women.

    Once every 3 months injectable regimen for postmenopausal osteoporosis.
    Intravenous dosage
    Adult postmenopausal females  

    3 mg IV (over 15 to 30 seconds) every 3 months. Do not administer more often than every 3 months. Supplement with calcium and vitamin D if dietary intake is inadequate. If a dose is missed, administer the missed dose as soon as possible and schedule future injections every 3 months from that date. The optimal treatment duration has not been determined; reevaluate treatment on a periodic basis. For those patients at low risk for fracture, consider stopping ibandronate after 3 to 5 years. After discontinuation of therapy, periodically reassess fracture risk. Bisphosphonates are a first-line therapy for the treatment of osteoporosis in postmenopausal women.

    For corticosteroid-induced osteoporosis† in men and women.
    Oral dosage
    Adults

    150 mg PO once monthly on the same date each month. Supplement with calcium and vitamin D if dietary intake is inadequate. Per guidelines, only use in patients with moderate to high risk for fracture; not recommended if low fracture risk.

    Intravenous dosage
    Adults

    Safety and efficacy have not been established; oral therapy is preferred by expert guidelines. Various dose regimens have been used in trials. 2 mg given IV once every 3 months has been found effective for up to 2 years.

    For osteoporosis prophylaxis.
    Once monthly oral regimen for prevention of postmenopausal osteoporosis.
    Oral dosage
    Adult postmenopausal females

    150 mg PO once monthly on the same date each month. Supplement calcium and vitamin D if dietary intake is inadequate. The optimal treatment duration has not been determined; reevaluate treatment on a periodic basis. For those patients at low risk for fracture, consider stopping ibandronate after 3 to 5 years. After discontinuation of therapy, continue to periodically reassess fracture risk.

    Once monthly oral regimen for corticosteroid-induced osteoporosis prophylaxis† in men and women.
    Oral dosage
    Adults

    150 mg PO once monthly on the same date each month. Supplement with calcium and vitamin D if dietary intake is inadequate. The optimal treatment duration has not been determined; reevaluate treatment on a periodic basis. For those patients at low risk for fracture, consider stopping ibandronate after 3 to 5 years. Per guidelines, only use in patients with moderate to high risk for fracture; not recommended if low fracture risk.

    For the treatment of Paget's disease†.
    Intravenous dosage
    Adults

    Safety and efficacy have not been established; ibandronate has only been studied for short-term control of Paget's disease. Single doses of 2 mg IV (over 15 to 30 seconds) or as a 6 mg IV infusion have been reported. No long-term clinical trials exist. Guidelines recommend other bisphosphonates (e.g., zoledronic acid) preferentially for Paget's disease due to long-term data with those medications at reducing pain and lytic lesions and improving quality of life.

    For the treatment of hypercalcemia† of malignancy.
    Intravenous dosage
    Adults

    Safety and efficacy have not been established; limited data reports in literature. In one comparator study, patients (n = 72) received ibandronate 2 mg or 4 mg as an IV infusion given over 2 hours or a pamidronate IV infusion (15 to 90 mg), with dosage of each agent was chosen according to the baseline degree of hypercalcemia. The most common dosage of ibandronate was a 4 mg IV infusion. Ibandronate and pamidronate resulted in similar efficacy and tolerability.

    For the prevention of adverse skeletal events due to bone metastases† in selected cancer patients (e.g., breast cancer).
    Oral dosage
    Adults

    50 mg PO once daily; this dosage is approved in Europe. This dosage form is not available in the U.S. Efficacy in reducing fracture rates (vertebral and non-vertebral) and bone pain was demonstrated in breast cancer patients.

    Intravenous dosage
    Adults

    6 mg IV infusion (over at least 15 minutes, and longer if renal impairment is present) given every 3 to 4 weeks. This dosage is approved in Europe. This dosage form is not available in the U.S. Efficacy in reducing fracture rates (vertebral and non-vertebral) and bone pain was demonstrated in breast cancer patients.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    2.5 mg/day PO, 150 mg/month PO, or 3 mg IV every 3 months for osteoporosis-related indications; for selected off-label indications, doses as large as 50 mg/day PO or 6 mg IV infusion as a single dose have been used.

    Geriatric

    2.5 mg/day PO, 150 mg/month PO, or 3 mg IV every 3 months for osteoporosis-related indications; for selected off-label indications, doses as large as 50 mg/day PO or 6 mg IV infusion as a single dose have been used.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    Infants

    Safety and efficacy have not been established.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No dosage adjustment required.

    Renal Impairment

    CrCl 30 mL/minute or more: Dosage adjustments are not necessary.
    CrCl less than 30 mL/minute: Use not recommended.
    For off-label indications and dosage forms, different renal dosing and administration recommendations apply.

    ADMINISTRATION

    Oral Administration

    Administer in the morning with a full glass of plain water (180 to 240 mL or 6 to 8 ounces) at least 1 hour before the first food, beverage, or medication of the day. Administering on an empty stomach is critical to drug effectiveness and the avoidance of selected side effects. At least 1 hour should elapse after an ibandronate dose before administering any other oral drugs.
    To avoid esophageal irritation, the patient should not lie down for at least 1 hour after administering the dose. Do not administer at bedtime or before arising.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. Do not use the prefilled syringe if particulate matter or discoloration is present.
    Take precautions to prevent allergic reactions by ensuring appropriate monitoring and medical support are available during administration.

    Intravenous Administration

    Intravenous ibandronate must be administered by a health care professional.
    Ibandronate is administered every 3 months; do not give more often than every 3 months.
    Ibandronate is available in 3 mg/3 mL prefilled syringes. The prefilled syringes are for single use only; discard unused portion. Use the needle provided by the manufacturer for drug administration.
    Administer via IV injection only. Do not administer by another route, especially intraarterially or paravenously, as this could lead to tissue damage.
    Do not mix the injection with calcium-containing solutions or other intravenously administered drugs.
    Administer IV over 15 to 30 seconds.[31826]

    STORAGE

    Boniva:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Extravasation, history of angioedema, intraarterial administration, phosphonate hypersensitivity, requires a specialized care setting

    Oral and parenteral ibandronate use is contraindicated in any patient with a history of angioedema, serious rash, anaphylaxis or another severe hypersensitivity reaction to the drug or product excipients. Allergic reactions including anaphylactic reaction/shock with fatalities, angioedema, bronchospasm, asthma exacerbations, rash, Stevens-Johnson syndrome, erythema multiforme, and dermatitis bullous have been reported. If anaphylactic or another severe hypersensitivity/allergic reaction occurs, immediately discontinue ibandronate and initiate appropriate treatment. Ibandronate should be used cautiously in patients with known phosphonate hypersensitivity.[29558] [31826] Ibandronate injection therapy requires a specialized care setting. Proper medical support and monitoring measures should be readily available when the ibandronate injection is administered in case there is hypersensitivity or another severe reaction.[31826] Injectable ibandronate must be administered by the intravenous route only; avoid other injectable routes. If ibandronate undergoes intraarterial administration or paravenous administration, extravasation or tissue damage may occur.[31826]

    Achalasia, dysphagia, esophageal stricture, esophagitis, gastritis, gastroesophageal reflux disease (GERD), GI disease, GI perforation, hiatal hernia, inability to stand or sit upright

    A history of GI disease is an independent risk factor for the development of GI adverse reactions during oral bisphosphonate therapy. Oral ibandronate should be used with caution in patients with esophageal and GI disease, including dysphagia, esophagitis, gastritis, gastroesophageal reflux disease (GERD), hiatal hernia, duodenitis, ulcers, or GI perforation. Use of such formulations are contraindicated in patients with abnormalities of the esophagus which delay esophageal emptying such as esophageal stricture or achalasia. Further, use of orally administered ibandronate is contraindicated in patients with an inability to stand or sit upright for at least 60 minutes after dose administration as the risk of esophagitis and esophageal ulceration/erosion appears to be greater in patients who lay down after taking this medicine. Prescribers and health care professionals should closely monitor patients for any signs or symptoms an esophageal reaction. Advise patients to discontinue ibandronate and seek medical attention if they develop dysphagia, odynophagia, or retrosternal pain. The risk of esophageal reactions increases in patients who do not follow the administration instructions. It is very important that patients understand and follow these instructions; direct observation may be required in those who cannot independently follow dosing instructions due to mental disability. In 2011, the FDA announced an ongoing review of data from published studies to evaluate whether use of oral bisphosphonate drugs is associated with an increased risk of esophageal cancer. There have been conflicting findings from studies evaluating this risk. At the time of the announcement, FDA states that the benefits of oral bisphosphonate drugs in reducing the risk of serious fractures in people with osteoporosis continue to outweigh their potential risks.

    Diabetes mellitus, hypertension, multiple myeloma, renal failure, renal impairment

    Ibandronate is not recommended in patients with severe renal impairment as the drug will likely accumulate. No dosage adjustment is recommended by the manufacturer if creatinine clearance is > 30 ml/min (mild to moderate renal insufficiency). Until further evidence is available, ibandronate is not recommended for patients with creatinine clearance < 30 ml/min (renal failure). Specific precautions pertain to intravenous use. Treatment with other intravenous bisphosphonates (i.e., pamidronate and zoledronic acid) has been associated with renal toxicity manifested as deterioration in renal function (i.e., decreased creatinine clearance) and in rare cases, acute renal failure. The risk of serious renal toxicity with these bisphosphonates appears to be inversely related to the rate of drug administration. No cases of acute renal failure were observed during controlled clinical trials when parenteral ibandronate was administered as an IV bolus over 15—30 seconds; however, acute renal failure has been reported during post-marketing use. Patients who receive ibandronate injection should have a serum creatinine measured prior to each dose. Patients with concomitant diseases that have the potential for adverse effects on the kidney (i.e., pre-existing renal impairment, dehydration, multiple myeloma, advanced cancers, diabetes mellitus, and hypertension), or patients that are using other drugs with the potential for nephrotoxicity (i.e., NSAIDs, radiopaque contrast media, and aminoglycosides) should be assessed during treatment with ibandronate as clinically necessary. If deterioration in kidney function occurs, ibandronate should be withheld. About 50% of an IV dose is excreted in the urine. In humans, any ibandronate not deposited in bone is rapidly excreted.

    Hypocalcemia, vitamin D deficiency

    Preexistent hypocalcemia is a contraindication and must be corrected before initiating ibandronate therapy. Similarly, vitamin D deficiency must be pretreated. Adequate intake of calcium and vitamin D are essential. This is most important for patients with Paget's disease who are to receive ibandronate. Ibandronate can decrease serum calcium and phosphate in these patients, who may have a higher rate of bone turnover.

    Children, infants, neonates

    Safety and efficacy of ibandronate have not been established in neonates, infants, children, or adolescents. Bisphosphonates have been used successfully in children for treatment of specific disease states (i.e., hypercalcemia of malignancy, idiopathic or glucocorticoid induced osteoporosis, osteogenesis imperfecta, Paget's disease). However, extreme caution must be used to ensure appropriate use in children; excessive doses of bisphosphonates may compromise skeletal quality during growth, despite concomitant increases in bone density. In a case report, inappropriate and excessive doses of pamidronate in a child resulted in osteopetrosis (abnormally dense and misshapen bone predisposed to fracture). It may be advisable to monitor biochemical markers of skeletal turnover when bisphosphonates are used in children to help assure clinicians that skeletal resorption is not excessively suppressed.

    Geriatric

    In clinical trials of oral ibandronate 52% of the patients studied were over 65 years of age, and 10% were over 75 years of age. Fifty-one percent (51%) of patients were over 65 years of age in clinical trials of ibandronate injection. No overall differences in effectiveness or safety were observed between these patients and younger patients but greater sensitivity in some older individuals cannot be ruled out. Geriatric patients may be at increased risk for the development of adverse GI reactions during ibandronate therapy. Increased age has been identified as an independent risk factor particularly for GI perforations, ulcers, or bleeding, but not necessarily esophageal events, with other bisphosphonates. The federal Omnibus Budget Reconciliation Act (OBRA) regulates the use of medications in residents of long-term care facilities. The OBRA guidelines state that bisphosphonates must be taken according to very specific directions, including time of day, position, and timing relative to other medications and food. Patients receiving these medications should be monitored closely for GI complications (e.g., esophageal or gastric erosion). Potential adverse effects of bisphosphonates include dysphagia, esophagitis, gastritis, or esophageal and gastric ulcers, particularly when used in combination with oral corticosteroids, aspirin, or other NSAIDs.

    Hypoparathyroidism

    Ibandronate should be used cautiously in patients with a history of hypoparathyroidism, due to an increased risk of hypocalcemia.

    Pregnancy

    Ibandronate is not indicated for use in women of reproductive potential. There are no data of ibandronate use during human pregnancy to inform of any drug-associated risks. Based on animal studies and the known class effects of bisphosphonates, fetal harm may occur. Reproductive studies in animals indicate that ibandronate may be associated with increased incidence of fetal renal pelvis ureter (RPU) syndrome, impaired infant neuromuscular development, maternal hypocalcemia, postimplantation fetal loss, dystocia and maternal periparturient death, and maternal and fetal death.

    Breast-feeding

    Ibandronate is not indicated in women of reproductive potential; use during breast-feeding is not recommended due to the potential for serious adverse events in a breastfed infant. There are no data on the presence of ibandronate in human milk, the effects on the breastfed infant, or the effects on milk production. Ibandronate was excreted into the milk of lactating rats after intravenous administration and remained present in rat breast milk for 2 to 24 hours after dose administration; the milk concentration averaged 1.5 times plasma concentrations.

    Anemia, chemotherapy, coagulopathy, corticosteroid therapy, dental disease, dental work, infection

    Osteonecrosis of the jaw has been reported in patients with cancer receiving treatment regimens which included bisphosphonates (most commonly pamidronate and zoledronic acid), but also occasionally in patients receiving chronic oral bisphosphonate therapy for osteoporosis, including ibandronate. The risk may increase with duration of exposure to the bisphosphonate. In patients with cancer receiving intravenous bisphosphonates, many patients were also receiving chemotherapy and corticosteroids. The majority of reported cases have been associated with dental procedures, such as tooth extraction, and many of these patients had signs of local infection including osteomyelitis; however, cases have appeared spontaneously. It would be prudent for all patients including those with concomitant risk factors (e.g. anemia, cancer, chemotherapy, coagulopathy, corticosteroid therapy, dental disease, infection, poor oral hygiene) initiating bisphosphonate therapy to receive a dental examination with appropriate preventive dentistry and correction of dental complications prior to beginning treatment. Preventive measures such as these as well as continued regular follow-up with a dentist during bisphosphonate therapy are recommended by the American Academy of Oral Medicine as the best way to minimize the risk of osteonecrosis. Invasive dental procedures should be avoided, if possible, during treatment, but if they are necessary, should be performed by an experienced dentist with close patient follow-up. If osteonecrosis of the jaw does develop during bisphosphonate therapy, it should be noted that dental surgery may exacerbate the condition. For patients requiring dental work, no data are available to suggest whether discontinuation of bisphosphonate treatment reduces the risk of osteonecrosis of the jaw. In addition, discontinuing the bisphosphonate once osteonecrosis develops is controversial as the estimated half-life of bisphosphonates in the bone is years.

    Laboratory test interference

    Bisphosphonates are known to interfere with the use of bone-imaging agents. Specific studies with ibandronate regarding this laboratory test interference have not been performed.

    ADVERSE REACTIONS

    Severe

    uveitis / Delayed / 0-0.1
    atrial fibrillation / Early / Incidence not known
    Stevens-Johnson syndrome / Delayed / Incidence not known
    angioedema / Rapid / Incidence not known
    bronchospasm / Rapid / Incidence not known
    anaphylactic shock / Rapid / Incidence not known
    erythema multiforme / Delayed / Incidence not known
    GI perforation / Delayed / Incidence not known
    esophageal ulceration / Delayed / Incidence not known
    peptic ulcer / Delayed / Incidence not known
    esophageal stricture / Delayed / Incidence not known
    GI bleeding / Delayed / Incidence not known
    visual impairment / Early / Incidence not known
    osteonecrosis / Delayed / Incidence not known
    bone fractures / Delayed / Incidence not known
    renal failure (unspecified) / Delayed / Incidence not known

    Moderate

    hypertension / Early / 5.3-7.3
    hypercholesterolemia / Delayed / 1.5-4.8
    constipation / Delayed / 2.5-4.1
    cystitis / Delayed / 3.4-3.4
    erythema / Early / 1.3-2.8
    gastritis / Delayed / 1.9-2.2
    depression / Delayed / 1.3-2.2
    hot flashes / Early / Incidence not known
    dysphagia / Delayed / Incidence not known
    esophagitis / Delayed / Incidence not known
    oral ulceration / Delayed / Incidence not known
    melena / Delayed / Incidence not known
    bone pain / Delayed / Incidence not known
    conjunctivitis / Delayed / Incidence not known
    ocular inflammation / Early / Incidence not known
    elevated hepatic enzymes / Delayed / Incidence not known
    thrombocytopenia / Delayed / Incidence not known
    hypercalciuria / Delayed / Incidence not known
    hypomagnesemia / Delayed / Incidence not known
    hypophosphatemia / Delayed / Incidence not known
    hypocalcemia / Delayed / Incidence not known

    Mild

    arthralgia / Delayed / 3.5-14.0
    back pain / Delayed / 4.3-13.5
    dyspepsia / Early / 3.6-11.9
    fever / Early / 1.1-10.0
    abdominal pain / Early / 5.1-7.8
    diarrhea / Early / 2.4-6.8
    headache / Early / 2.6-6.5
    myalgia / Early / 0.8-5.7
    nausea / Early / 2.1-5.1
    pharyngitis / Delayed / 2.5-4.3
    infection / Delayed / 4.3-4.3
    dizziness / Early / 1.0-3.7
    asthenia / Delayed / 3.5-3.5
    vertigo / Early / 3.0-3.0
    pruritus / Rapid / 1.3-2.8
    rash / Early / 1.3-2.8
    maculopapular rash / Early / 1.3-2.8
    vomiting / Early / 2.7-2.7
    insomnia / Early / 0.8-2.6
    injection site reaction / Rapid / 0-2.0
    muscle cramps / Delayed / 1.8-2.0
    diaphoresis / Early / Incidence not known
    pyrosis (heartburn) / Early / Incidence not known
    dysgeusia / Early / Incidence not known
    gastroesophageal reflux / Delayed / Incidence not known
    musculoskeletal pain / Early / Incidence not known
    ocular pain / Early / Incidence not known

    DRUG INTERACTIONS

    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Aluminum Hydroxide: (Moderate) Separating times of administration of the oral bisphosphonate from aluminum-containing medications will maximize absorption and clinical benefit. Aluminum hydroxide will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any aluminum containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any aluminum containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any aluminum containing product.
    Aluminum Hydroxide; Magnesium Carbonate: (Moderate) Separating times of administration of the oral bisphosphonate from aluminum-containing medications will maximize absorption and clinical benefit. Aluminum hydroxide will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any aluminum containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any aluminum containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any aluminum containing product.
    Aluminum Hydroxide; Magnesium Hydroxide: (Moderate) Separating times of administration of the oral bisphosphonate from aluminum-containing medications will maximize absorption and clinical benefit. Aluminum hydroxide will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any aluminum containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any aluminum containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any aluminum containing product.
    Aluminum Hydroxide; Magnesium Hydroxide; Simethicone: (Moderate) Separating times of administration of the oral bisphosphonate from aluminum-containing medications will maximize absorption and clinical benefit. Aluminum hydroxide will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any aluminum containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any aluminum containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any aluminum containing product.
    Aluminum Hydroxide; Magnesium Trisilicate: (Moderate) Separating times of administration of the oral bisphosphonate from aluminum-containing medications will maximize absorption and clinical benefit. Aluminum hydroxide will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any aluminum containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any aluminum containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any aluminum containing product.
    Amikacin: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like the aminoglycosides may increase the risk of developing nephrotoxicity.
    Aminoglycosides: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like the aminoglycosides may increase the risk of developing nephrotoxicity.
    Amlodipine; Celecoxib: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Aspirin, ASA: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Aspirin, ASA; Caffeine: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Aspirin, ASA; Carisoprodol: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Aspirin, ASA; Citric Acid; Sodium Bicarbonate: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use. (Moderate) Sodium bicarbonate can reduce the absorption of the oral bisphosphonates. Wait at least 30 minutes after oral alendronate, 1 hour after ibandronate, and 2 hours after oral etidronate, risedronate, or tiludronate before taking a sodium bicarbonatecontaining product.
    Aspirin, ASA; Dipyridamole: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Aspirin, ASA; Omeprazole: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Aspirin, ASA; Oxycodone: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Aspirin, ASA; Pravastatin: (Moderate) Aspirin, ASA use is associated with esophageal and/or gastric irritation, and GI ulceration. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. In clinical trials, aspirin use along with bisphosphonates increased the risk of GI events in some patients; however, some clinical trials of bisphosphonates have not reported increased rates of GI adverse events with aspirin co-use. Exercise caution when administering aspirin with a bisphosphonate. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, and monitor renal function during combined use.
    Bumetanide: (Moderate) When the intravenous formulation of ibandronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
    Bupivacaine; Meloxicam: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Calcium Acetate: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Calcium Carbonate: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Calcium Carbonate; Famotidine; Magnesium Hydroxide: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Calcium Carbonate; Magnesium Hydroxide: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Calcium Carbonate; Risedronate: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Calcium Carbonate; Simethicone: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Calcium Chloride: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Calcium Gluconate: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Calcium: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Calcium; Vitamin D: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Celecoxib: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Chromium: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Cyclosporine: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like cyclosporine may increase the risk of developing nephrotoxicity.
    Deferasirox: (Moderate) Because gastric ulceration and GI bleeding have been reported in patients taking deferasirox, use caution when coadministering with other drugs known to increase the risk of peptic ulcers or gastric hemorrhage including ibandronate.
    Diclofenac: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Diclofenac; Misoprostol: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Diflunisal: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Diphenhydramine; Ibuprofen: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Diphenhydramine; Naproxen: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Ethacrynic Acid: (Moderate) When the intravenous formulation of ibandronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
    Etodolac: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Famotidine; Ibuprofen: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Fenoprofen: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Ferric Maltol: (Moderate) Separating times of administration of the oral bisphosphonate from iron-containing supplements and medications will maximize absorption and clinical benefit. Iron will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any iron containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any iron containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Flurbiprofen: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Food: (Major) Ibandronate oral absorption becomes almost negligible if ibandronate is taken within 2 hours of breakfast. Even orange juice or coffee can reduce bioavailability. The ingestion of high-calcium foods can interfere with the absorption of ibandronate, and should not be eaten before or for at least 60 minutes after, administration of ibandronate. To achieve maximum possible bioavailability, ibandronate must be taken in the fasting state and at least 2 hours before a standard breakfast.
    Furosemide: (Moderate) When the intravenous formulation of ibandronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
    Gentamicin: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like the aminoglycosides may increase the risk of developing nephrotoxicity.
    Hetastarch; Dextrose; Electrolytes: (Moderate) Magnesium-containing products may significantly reduce the absorption of ibandronate. All medications should be administered at least 60 minutes after an ibandronate dose to help prevent these absorption interactions. However, some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after ibandronate or at a completely different time of day. (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Hydrocodone; Ibuprofen: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Ibuprofen: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Ibuprofen; Oxycodone: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Ibuprofen; Pseudoephedrine: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Indomethacin: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Iron Salts: (Moderate) Separating times of administration of the oral bisphosphonate from iron-containing supplements and medications will maximize absorption and clinical benefit. Iron will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any iron containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any iron containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Iron: (Moderate) Separating times of administration of the oral bisphosphonate from iron-containing supplements and medications will maximize absorption and clinical benefit. Iron will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any iron containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any iron containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Kanamycin: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like the aminoglycosides may increase the risk of developing nephrotoxicity.
    Ketoprofen: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Ketorolac: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Lansoprazole; Naproxen: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Lanthanum Carbonate: (Moderate) To limit absorption problems, the oral bisphosphonates should not be taken within 2 hours of dosing with lanthanum carbonate. Oral drugs known to interact with cationic antacids, like the oral bisphosphonates, may also be bound by lanthanum carbonate. Separating times of administration will maximize absorption and clinical benefit of the bisphosphonate. Separate the times of administration appropriately. Monitor the patient's clinical status and bone density as recommended to ensure the appropriate response to bisphosphonate therapy is obtained.
    Loop diuretics: (Moderate) When the intravenous formulation of ibandronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
    Magnesium Citrate: (Moderate) Do not administer oral magnesium-containing products within 2 hours of oral bisphosphonates; oral magnesium may significantly reduce the absorption of the oral bisphosphonates (e.g., alendronate, etidronate, ibandronate, risedronate, or tiludronate). All medications should be administered at least 30 minutes after an alendronate or risedronate dose, and at least 1 hour after an ibandronate dose to help prevent absorption interactions. Some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after these drugs or at a different time of day.
    Magnesium Salts: (Moderate) Magnesium-containing products may significantly reduce the absorption of ibandronate. All medications should be administered at least 60 minutes after an ibandronate dose to help prevent these absorption interactions. However, some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after ibandronate or at a completely different time of day.
    Magnesium: (Moderate) Magnesium-containing products may significantly reduce the absorption of ibandronate. All medications should be administered at least 60 minutes after an ibandronate dose to help prevent these absorption interactions. However, some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after ibandronate or at a completely different time of day.
    Meclofenamate Sodium: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Mefenamic Acid: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Meloxicam: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Nabumetone: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Naproxen: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Naproxen; Esomeprazole: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Naproxen; Pseudoephedrine: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Non-Ionic Contrast Media: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs, such as radiopaque contrast agents, may increase the risk of developing nephrotoxicity.
    Nonsteroidal antiinflammatory drugs: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Norethindrone Acetate; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Separating times of administration of the oral bisphosphonate from iron-containing supplements and medications will maximize absorption and clinical benefit. Iron will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any iron containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any iron containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Norethindrone; Ethinyl Estradiol; Ferrous fumarate: (Moderate) Separating times of administration of the oral bisphosphonate from iron-containing supplements and medications will maximize absorption and clinical benefit. Iron will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any iron containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any iron containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Omeprazole; Sodium Bicarbonate: (Moderate) Sodium bicarbonate can reduce the absorption of the oral bisphosphonates. Wait at least 30 minutes after oral alendronate, 1 hour after ibandronate, and 2 hours after oral etidronate, risedronate, or tiludronate before taking a sodium bicarbonatecontaining product.
    Oxaprozin: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Paromomycin: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like the aminoglycosides may increase the risk of developing nephrotoxicity.
    Piroxicam: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Plazomicin: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like the aminoglycosides may increase the risk of developing nephrotoxicity.
    Polycarbophil: (Moderate) Coadministration of ibandronate with calcium polycarbophil can interfere with the oral absorption of ibandronate; do not administer calcium polycarbophil within 60 minutes of ibandronate. Each 625 mg of calcium polycarbophil contains a substantial amount of calcium (approximately 125 mg).
    Polysaccharide-Iron Complex: (Moderate) Separating times of administration of the oral bisphosphonate from iron-containing supplements and medications will maximize absorption and clinical benefit. Iron will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any iron containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any iron containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Pyridoxine, Vitamin B6: (Moderate) Separating times of administration of the oral bisphosphonate from calcium-containing supplements and medications will maximize absorption and clinical benefit. Calcium will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any calcium containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any calcium containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Rofecoxib: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Sodium Bicarbonate: (Moderate) Sodium bicarbonate can reduce the absorption of the oral bisphosphonates. Wait at least 30 minutes after oral alendronate, 1 hour after ibandronate, and 2 hours after oral etidronate, risedronate, or tiludronate before taking a sodium bicarbonatecontaining product.
    Sodium Ferric Gluconate Complex; ferric pyrophosphate citrate: (Moderate) Separating times of administration of the oral bisphosphonate from iron-containing supplements and medications will maximize absorption and clinical benefit. Iron will interfere with the absorption of the orally administered bisphosphonates alendronate, etidronate, ibandronate, risedronate, and tiludronate. At least 30 minutes should elapse after the oral administration of alendronate before taking any iron containing product. At least 1 hour should elapse after the oral administration of ibandronate before taking any iron containing product. At least 2 hours should elapse after the oral administration of etidronate, risedronate, or tiludronate before administering any calcium containing product.
    Sodium Sulfate; Magnesium Sulfate; Potassium Chloride: (Moderate) Magnesium-containing products may significantly reduce the absorption of ibandronate. All medications should be administered at least 60 minutes after an ibandronate dose to help prevent these absorption interactions. However, some recommend that divalent cation-containing products should preferentially be taken at least 2 hours after ibandronate or at a completely different time of day.
    Streptomycin: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like the aminoglycosides may increase the risk of developing nephrotoxicity.
    Sulindac: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Sumatriptan; Naproxen: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Tacrolimus: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like tacrolimus may increase the risk of developing nephrotoxicity.
    Tobramycin: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like the aminoglycosides may increase the risk of developing nephrotoxicity.
    Tolmetin: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Torsemide: (Moderate) When the intravenous formulation of ibandronate is used for the treatment of hypercalcemia of malignancy, combination therapy with loop diuretics should be used with caution in order to avoid hypocalcemia. In patients with hypercalcemia of malignancy, the initial treatment typically includes the use of loop diuretics, in combination with saline hydration, however, diuretic therapy should not be employed prior to correction of hypovolemia and dehydration.
    Valdecoxib: (Moderate) Exercise caution when administering an NSAID with a bisphosphonate. Monitor for the presence of GI complaints, including potential GI ulceration and bleeding, as well as renal function, during combined use. Nonsteroidal antiinflammatory drugs (NSAIDs) are associated with esophageal and/or gastric irritation, GI ulceration. a risk of nephrotoxicity, and decreased bone mineral density. Bisphosphonates may cause GI adverse events and occasionally, renal dysfunction. Though patients receiving intravenously administered bisphosphonates have a decreased incidence of GI adverse effects as compared to those taking orally administered bisphosphonates, nephrotoxicity is possible, and GI events are rarely reported.
    Vancomycin: (Moderate) Theoretically, coadministration of intravenous ibandronate with other potentially nephrotoxic drugs like vancomycin may increase the risk of developing nephrotoxicity.

    PREGNANCY AND LACTATION

    Pregnancy

    Ibandronate is not indicated for use in women of reproductive potential. There are no data of ibandronate use during human pregnancy to inform of any drug-associated risks. Based on animal studies and the known class effects of bisphosphonates, fetal harm may occur. Reproductive studies in animals indicate that ibandronate may be associated with increased incidence of fetal renal pelvis ureter (RPU) syndrome, impaired infant neuromuscular development, maternal hypocalcemia, postimplantation fetal loss, dystocia and maternal periparturient death, and maternal and fetal death.

    Ibandronate is not indicated in women of reproductive potential; use during breast-feeding is not recommended due to the potential for serious adverse events in a breastfed infant. There are no data on the presence of ibandronate in human milk, the effects on the breastfed infant, or the effects on milk production. Ibandronate was excreted into the milk of lactating rats after intravenous administration and remained present in rat breast milk for 2 to 24 hours after dose administration; the milk concentration averaged 1.5 times plasma concentrations.

    MECHANISM OF ACTION

    Ibandronate has pharmacologic actions similar to those of other bisphosphonates, although, compared to other bisphosphonates, ibandronate is more potent than alendronate, pamidronate, and clodronate, but is less potent than risedronate. Bone resorption releases excessive amounts of calcium into the blood. The double phosphonate group common to all bisphosphonates allows them to bind to calcified bone matrix. Adsorption of ibandronate to hydroxyapatite crystals in the mineralized matrix reduces solubility of the matrix and therefore osteoclastic resorption. A stable bone matrix will also prevent signaling to osteoclasts to migrate to the site. Ibandronate blocks attachment of osteoclast precursors to mineralized matrix, preventing transformation into mature, functioning osteoclasts. Ibandronate reduces bone turnover and, when used in combination with adequate hydration to increase renal excretion of calcium, reduces serum calcium concentrations. Serum calcium concentrations, urinary calcium/creatinine ratio, and hydroxyproline/creatinine ratio usually return to within or below normal within the first week after treatment.
     
    In multiple myeloma, myeloma cells release soluble factors that activate osteoclasts to resorb bone. In multiple myeloma animal models, ibandronate inhibited osteoclast stimulatory activity and the development of lytic lesions, but not eventual tumor burden. Inhibition of enzymes in the mevalonate pathway appears to explain the effectiveness of ibandronate in multiple myeloma. It is expected that, like other bisphosphonates, ibandronate decreases the extent of accelerated bone resorption that results from osteoclast hyperactivity. Hypercalcemia is a common problem affecting cancer patients. Malignancy-associated hypercalcemia arises from accelerated bone resorption. This form of hypercalcemia could result from a direct skeletal action by various tumors inducing osteoclast hyperactivity. Ibandronate does not lower the level of parathyroid hormone-related protein (PTHrP) in patients with hypercalcemia of malignancy. Ibandronate inhibits bone resorption without inhibiting bone formation or mineralization. The drug has no antineoplastic properties.
     
    Like other bisphosphonates, the exact mechanism of ibandronate's therapeutic effect in patients with Paget's disease has not been clearly established. Paget's disease is a progressive, idiopathic disease of bone. Increasing numbers of unusually large osteoclasts are produced at affected sites. Increased bone resorption follows, which is compensated for by an increase in new bone formation. This new bone is inferior and often deformed, and can fracture easily. Bisphosphonates are believed to reduce the solubility of mineralized bone matrix by adsorption to hydroxyapatite crystals in the matrix. The matrix becomes less soluble and resistant to osteoclastic resorption. Ibandronate, and other bisphosphonates, can also block the formation of mature osteoclasts by affecting the attachment of osteoclast precursors to the mineralized matrix.

    PHARMACOKINETICS

    Ibandronate is administered orally and intravenously.  After absorption, it is rapidly redistributed to bone or undergoes urinary excretion. Ibandronate is 86—99% bound to protein in human plasma; an estimated 40—50% of the circulating dose is bound to the bone. There is no evidence that any metabolism takes place. The portion that is not removed from the circulation via bone absorption is eliminated unchanged by the kidney (approximately 50—60% of the absorbed dose). Any unabsorbed orally-administered ibandronate is eliminated unchanged in the feces. The apparent half-life range is broad, generally 5—60 hours, and dependent on the dosage studied and on assay sensitivity. However, early plasma concentrations fall quickly, reaching 10% of peak values within 3 and 8 hours after intravenous or oral administration, respectively.
     
    Affected cytochrome P450 isoenzymes: none

    Oral Route

    With oral administration, ibandronate is absorbed in the upper gastrointestinal tract. Oral absorption is poor, with a bioavailability of approximately 0.6% compared to intravenous dosing. Absorption becomes almost negligible if ibandronate is taken within 1 hour of breakfast. To achieve maximum possible bioavailability, ibandronate must be taken in the fasting state and at least 1 hour before a standard breakfast. Concomitantly administered cations (e.g., calcium, magnesium) are likely to reduce bioavailability. After an oral dose, the time to maximum observed plasma ibandronate concentrations (Cmax) ranged from 0.5 to 2 hours (median 1 hour) in fasted healthy postmenopausal women.