CLASSES

Melatonin Receptor Agonists

DEA CLASS

Rx

DESCRIPTION

Melatonin receptor agonist
Used for non-24-hour sleep-wake disorder and nighttime sleep disturbances in Smith-Magenis Syndrome
May take weeks or months for drug effect to occur in non-24 due to variable circadian rhythms

COMMON BRAND NAMES

HETLIOZ, HETLIOZ LQ

HOW SUPPLIED

HETLIOZ LQ Oral Susp: 1mL, 4mg
HETLIOZ/Tasimelteon Oral Cap: 20mg

DOSAGE & INDICATIONS

MAXIMUM DOSAGE

20 mg/day PO.

20 mg/day PO.

16 to 17 years: 20 mg/day PO.
13 to 15 years weighing more than 28 kg: 20 mg/day PO.
13 to 15 years weighing 28 kg or less: 0.7 mg/kg/day PO.

3 to 12 years weighing more than 28 kg: 20 mg/day PO.
3 to 12 years weighing 28 kg or less: 0.7 mg/kg/day PO.
1 to 2 years: Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

DOSING CONSIDERATIONS

Tasimelteon is not recommended in patients with severe hepatic impairment (Child-Pugh Class C). Dosage adjustment is not necessary in patients with mild or moderate hepatic impairment.

No dosage adjustment necessary.
 
Hemodialysis
Hemodialysis is effective at clearing tasimelteon and the majority of its metabolites; however, it is not known if hemodialysis will reduce exposure.

ADMINISTRATION

Administer without food 1 hour before bedtime, at the same time every night.
If the patient is unable to take the drug at approximately the same time on a given night, they should skip that dose and take the next dose as scheduled.
Limit activities to those necessary to get ready for bed after the drug has been administered.

STORAGE

HETLIOZ:
- Protect from light
- Protect from moisture
- Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
HETLIOZ LQ:
- Refrigerate (between 36 and 46 degrees F)
- See package insert for detailed storage information

CONTRAINDICATIONS / PRECAUTIONS

Limit activity to that necessary for going to bed after taking tasimelteon. Avoid activities that require mental alertness, including driving or operating machinery, after taking tasimelteon. A single dose study indicated a trend towards additive effects of tasimelteon and alcohol on some psychomotor tests. Those with a history of alcoholism may not be appropriate candidates for tasimelteon therapy. Patients should be cautioned about the potential adverse effects of ethanol ingestion and ethanol intoxication during treatment with tasimelteon.

Tasimelteon is extensively metabolized in the liver; however, dosage adjustments are not necessary in patients with mild to moderate hepatic impairment. Because tasimelteon has not been studied in patients with severe hepatic disease, use is not recommended in this patient population.

Tasimelteon exposure is decreased by about 40% in smokers compared to non-smokers. Patients should be advised of the potential for reduced efficacy of the drug during tobacco smoking.

The risk of adverse reactions during treatment with tasimelteon may be increased in geriatric patients compared to younger adults due to an approximate 2-fold increase in exposure; however, the manufacturer does not recommend dosage adjustments based upon age. Further study in this patient population is needed. As with other melatonin receptor agonists, cognitive and behavioral changes are possible during treatment with tasimelteon. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). According to the OBRA guidelines, factors potentially causing insomnia should be evaluated before initiating a sedative (e.g., sleep environment, inadequate physical activity, provision of care disruptions, caffeine or medications, pain, and discomfort, or other underlying conditions that cause insomnia). Most cases of insomnia are associated with other underlying conditions. It is expected that non-pharmacologic interventions and maximized treatment of underlying conditions (if applicable) are implemented to address the causative factor(s). Initiation of sleep induction or maintenance medication should be preceded or accompanied by other interventions to attempt sleep improvement. Use all sleep medications by following the approved product labeling. The use of sedating medications for individuals with diagnosed sleep apnea requires careful assessment, documented clinical rationale, and close monitoring. Exceptions to OBRA include 1) single dose sedative use for a dental or medical procedure or 2) short-term sedative use during initiation of treatment for depression, pain, or other comorbid condition until symptoms improve or the underlying causative factor is identified or effectively treated. OBRA provides dosing guidance for most sedatives, including ramelteon. When a drug is being used to induce sleep or treat a sleep disorder, the facility should attempt periodic tapering of the medication or provide documentation of medical necessity per the OBRA guidelines.

Tasimelteon should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Available postmarketing case reports with use of tasimelteon in pregnant women are not sufficient to evaluate drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In pregnant rats, no embryofetal developmental toxicity was observed at exposures of up to 50 mg/kg/day (the no-effect dose), or approximately 25 times the human exposure at the maximum recommended human dose (MRHD) of 20 mg/day. Oral administration of tasimelteon at 50, 150, or 450 mg/kg/day to rats throughout organogenesis resulted in persistent reductions in body weight, delayed sexual maturation, and physical development, and neurobehavioral impairment in offspring at the highest dose tested which is approximately 220 times the MRHD based on body surface area. Reduced body weight in offspring was also observed at the mid-dose. It is not known what effect tasimelteon would have during labor or obstetric delivery.

There are no data on the presence of tasimelteon in human milk, the effects on the breastfed infant, or the effects on milk production. Caution is advisable when administering tasimelteon to a woman who is breast-feeding an infant. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for tasimelteon and any potential adverse effects on the breastfed infant from tasimelteon or the underlying maternal condition. 

Tasimelteon should be used cautiously in any patient who has a history of endocrine disease. Melatonin and another melatonin agonist, ramelteon, have been associated with an effect on reproductive hormones in adults (e.g., decreased testosterone levels and increased prolactin levels; hyperprolactinemia). It is not known what effect chronic or even chronic intermittent use of melatonin agonists may have on reproduction, or if tasimelteon would adversely impact fertility. When male and female rats were given tasimelteon at oral doses of 5, 50, or 500 mg/kg/day prior to and throughout mating and continuing in females to gestation day 7, estrus cycle disruption and decreased fertility were observed at all but the lowest dose tested. The no-effect dose for effects on female reproduction (5 mg/kg/day) is approximately 2 times the maximum recommended human dose (MHRD) based on body surface area. Advise patients to consult their health care providers if they experience one of the following: irregular menses or galactorrhea in females, decreased libido in either gender, or problems with fertility (infertility). Assessment of prolactin concentrations and testosterone concentrations should be considered as clinically appropriate. It is clear that endogenous melatonin plays an important role in the regulation of endocrine functions in the body, particularly the regulation of other hormones, but the effect of tasimelteon is not known.

ADVERSE REACTIONS

elevated hepatic enzymes / Delayed / 10.0-10.0

headache / Early / 17.0-17.0
abnormal dreams / Early / 10.0-10.0
nightmares / Early / 10.0-10.0
infection / Delayed / 7.0-7.0
drowsiness / Early / 10.0

DRUG INTERACTIONS

Acebutolol: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Acetaminophen; Aspirin, ASA; Caffeine: (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking melatonin or the melatonin analogs (ramelteon, tasimelteon) for sleep should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
Acetaminophen; Aspirin; Diphenhydramine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Acetaminophen; Caffeine: (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking melatonin or the melatonin analogs (ramelteon, tasimelteon) for sleep should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking tasimelteon. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking melatonin or the melatonin analogs (ramelteon, tasimelteon) for sleep should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
Acetaminophen; Caffeine; Pyrilamine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon. (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking melatonin or the melatonin analogs (ramelteon, tasimelteon) for sleep should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
Acetaminophen; Chlorpheniramine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Acetaminophen; Chlorpheniramine; Dextromethorphan: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Acetaminophen; Chlorpheniramine; Phenylephrine : (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Acetaminophen; Codeine: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking tasimelteon. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Acetaminophen; Dextromethorphan; Doxylamine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Acetaminophen; Diphenhydramine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Acetaminophen; Hydrocodone: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking tasimelteon. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Acetaminophen; Oxycodone: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Acetaminophen; Pamabrom; Pyrilamine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Acrivastine; Pseudoephedrine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Alfentanil: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Alprazolam: (Moderate) Concomitant administration of alprazolam with CNS-depressant drugs can potentiate the CNS effects of either agent.
Amobarbital: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as barbiturates or primidone, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of tasimelteon with another potent inducer of CYP3A4, tasimelteon exposure decreased by about 90%. Barbiturates also induce CYP1A2, a secondary metabolic pathway of tasimelteon.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as clarithromycin, should be avoided if possible. Because tasimelteon is partially metabolized via CYP3A4, a large increase in exposure of tasimelteon with the potential for adverse reactions is possible if these drugs are coadministered. During administration of tasimelteon and another potent CYP3A4 inhibitor, tasimelteon exposure increased by about 50%.
Apalutamide: (Major) Avoid coadministration of tasimelteon with apalutamide due to the potential for a large decrease in tasimelteon exposure resulting in reduced efficacy. Tasimelteon is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased tasimelteon exposure by about 90%.
Aprepitant, Fosaprepitant: (Moderate) Use caution if tasimelteon and aprepitant, fosaprepitant are used concurrently and monitor for an increase in tasimelteon-related adverse effects for several days after administration of a multi-day aprepitant regimen.Tasimelteon is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer and may increase plasma concentrations of tasimelteon. For example, a 5-day oral aprepitant regimen increased the AUC of another CYP3A4 substrate, midazolam (single dose), by 2.3-fold on day 1 and by 3.3-fold on day 5. After a 3-day oral aprepitant regimen, the AUC of midazolam (given on days 1, 4, 8, and 15) increased by 25% on day 4, and then decreased by 19% and 4% on days 8 and 15, respectively. As a single 125 mg or 40 mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.5-fold and 1.2-fold, respectively. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction. Fosaprepitant 150 mg IV as a single dose increased the AUC of midazolam (given on days 1 and 4) by approximately 1.8-fold on day 1; there was no effect on day 4. Less than a 2-fold increase in the midazolam AUC is not considered clinically important.
Aripiprazole: (Moderate) Due to the primary CNS effects of aripiprazole, caution should be used when aripiprazole is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics.
Armodafinil: (Moderate) Caution is recommended during concurrent use of tasimelteon and modafinil or armodafinil. Because tasimelteon is metabolized via CYP3A4 and CYP1A2, inducers of these isoenzymes, such as modafinil and armodafinil, may reduce the efficacy of tasimelteon.
Aspirin, ASA; Butalbital; Caffeine: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as barbiturates or primidone, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of tasimelteon with another potent inducer of CYP3A4, tasimelteon exposure decreased by about 90%. Barbiturates also induce CYP1A2, a secondary metabolic pathway of tasimelteon. (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking melatonin or the melatonin analogs (ramelteon, tasimelteon) for sleep should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
Aspirin, ASA; Butalbital; Caffeine; Codeine: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as barbiturates or primidone, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of tasimelteon with another potent inducer of CYP3A4, tasimelteon exposure decreased by about 90%. Barbiturates also induce CYP1A2, a secondary metabolic pathway of tasimelteon. (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking tasimelteon. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking melatonin or the melatonin analogs (ramelteon, tasimelteon) for sleep should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
Aspirin, ASA; Caffeine: (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking melatonin or the melatonin analogs (ramelteon, tasimelteon) for sleep should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
Aspirin, ASA; Caffeine; Orphenadrine: (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking melatonin or the melatonin analogs (ramelteon, tasimelteon) for sleep should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking tasimelteon. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Aspirin, ASA; Oxycodone: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Atazanavir: (Moderate) Caution is recommended during concurrent use of tasimelteon and atazanavir. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors, such as atazanavir, may increase exposure to tasimelteon with the potential for adverse reactions.
Atazanavir; Cobicistat: (Moderate) Caution is recommended during concurrent use of tasimelteon and atazanavir. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors, such as atazanavir, may increase exposure to tasimelteon with the potential for adverse reactions.
Atenolol: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Atenolol; Chlorthalidone: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Barbiturates: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as barbiturates or primidone, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of tasimelteon with another potent inducer of CYP3A4, tasimelteon exposure decreased by about 90%. Barbiturates also induce CYP1A2, a secondary metabolic pathway of tasimelteon.
Belladonna; Opium: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Bendroflumethiazide; Nadolol: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Benzhydrocodone; Acetaminophen: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Beta-blockers: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Betaxolol: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Bexarotene: (Moderate) Caution is recommended during concurrent use of tasimelteon and bexarotene. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inducers, such as bexarotene, may reduce the efficacy of tasimelteon.
Bisoprolol: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Brimonidine; Timolol: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Brompheniramine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Brompheniramine; Dextromethorphan; Guaifenesin: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Brompheniramine; Dextromethorphan; Phenylephrine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Brompheniramine; Phenylephrine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Brompheniramine; Pseudoephedrine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Brompheniramine; Pseudoephedrine; Dextromethorphan: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Buprenorphine: (Moderate) If concurrent use of tasimelteon and buprenorphine is necessary, consider a dose reduction of one or both drugs because of the potential for additive pharmacological effects. Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
Buprenorphine; Naloxone: (Moderate) If concurrent use of tasimelteon and buprenorphine is necessary, consider a dose reduction of one or both drugs because of the potential for additive pharmacological effects. Hypotension, profound sedation, coma, respiratory depression, or death may occur during co-administration of buprenorphine and other CNS depressants. Prior to concurrent use of buprenorphine in patients taking a CNS depressant, assess the level of tolerance to CNS depression that has developed, the duration of use, and the patient's overall response to treatment. Evaluate the patient's use of alcohol or illicit drugs. It is recommended that the injectable buprenorphine dose be halved for patients who receive other drugs with CNS depressant effects; for the buprenorphine transdermal patch, start with the 5 mcg/hour patch. Monitor patients for sedation or respiratory depression.
Butabarbital: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as barbiturates or primidone, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of tasimelteon with another potent inducer of CYP3A4, tasimelteon exposure decreased by about 90%. Barbiturates also induce CYP1A2, a secondary metabolic pathway of tasimelteon.
Butalbital; Acetaminophen: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as barbiturates or primidone, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of tasimelteon with another potent inducer of CYP3A4, tasimelteon exposure decreased by about 90%. Barbiturates also induce CYP1A2, a secondary metabolic pathway of tasimelteon.
Butalbital; Acetaminophen; Caffeine: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as barbiturates or primidone, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of tasimelteon with another potent inducer of CYP3A4, tasimelteon exposure decreased by about 90%. Barbiturates also induce CYP1A2, a secondary metabolic pathway of tasimelteon. (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking melatonin or the melatonin analogs (ramelteon, tasimelteon) for sleep should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
Butalbital; Acetaminophen; Caffeine; Codeine: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as barbiturates or primidone, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of tasimelteon with another potent inducer of CYP3A4, tasimelteon exposure decreased by about 90%. Barbiturates also induce CYP1A2, a secondary metabolic pathway of tasimelteon. (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking tasimelteon. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression. (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking melatonin or the melatonin analogs (ramelteon, tasimelteon) for sleep should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
Caffeine: (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking melatonin or the melatonin analogs (ramelteon, tasimelteon) for sleep should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
Caffeine; Sodium Benzoate: (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking melatonin or the melatonin analogs (ramelteon, tasimelteon) for sleep should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
Cannabidiol: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cannabidiol and tasimelteon. CNS depressants can potentiate the effects of cannabidiol.
Carbamazepine: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as carbamazepine, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of tasimelteon with another potent inducer of CYP3A4, tasimelteon exposure decreased by about 90%. Carbamazepine also induces CYP1A2, a secondary metabolic pathway of tasimelteon.
Carbinoxamine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Carbinoxamine; Phenylephrine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Carbinoxamine; Pseudoephedrine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Cariprazine: (Moderate) Due to the CNS effects of cariprazine, caution should be used when cariprazine is given in combination with other centrally-acting medications including benzodiazepines and other anxiolytics, sedatives, and hypnotics like tasimelteon.
Carteolol: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Carvedilol: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Celecoxib; Tramadol: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Cenobamate: (Moderate) Monitor for excessive sedation and somnolence during coadministration of cenobamate and tasimelteon. Concurrent use may result in additive CNS depression.
Cetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with tasimelteon should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Cetirizine; Pseudoephedrine: (Moderate) Concurrent use of cetirizine/levocetirizine with tasimelteon should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Chlophedianol; Dexbrompheniramine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Chloramphenicol: (Moderate) Caution is recommended during concurrent use of tasimelteon and chloramphenicol. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors, such as chloramphenicol, may increase exposure to tasimelteon with the potential for adverse reactions.
Chlorcyclizine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Chlorpheniramine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Chlorpheniramine; Codeine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon. (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking tasimelteon. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Chlorpheniramine; Dextromethorphan: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Chlorpheniramine; Dextromethorphan; Phenylephrine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon. (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking tasimelteon. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Chlorpheniramine; Hydrocodone: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon. (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking tasimelteon. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Chlorpheniramine; Phenylephrine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Chlorpheniramine; Pseudoephedrine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Cimetidine: (Moderate) Caution is recommended during concurrent use of tasimelteon and cimetidine. Because tasimelteon is metabolized via CYP3A4 and CYP1A2, use with CYP3A4 and CYP1A2 inhibitors, such as cimetidine, may increase exposure to tasimelteon and the potential for adverse reactions.
Ciprofloxacin: (Moderate) Caution is recommended during concurrent use of tasimelteon and enoxacin or ciprofloxacin. Because tasimelteon is partially metabolized via CYP1A2, use with CYP1A2 inhibitors, such as enoxacin or ciprofloxacin, may increase exposure to tasimelteon and the potential for adverse reactions.
Clarithromycin: (Major) Concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as clarithromycin, should be avoided if possible. Because tasimelteon is partially metabolized via CYP3A4, a large increase in exposure of tasimelteon with the potential for adverse reactions is possible if these drugs are coadministered. During administration of tasimelteon and another potent CYP3A4 inhibitor, tasimelteon exposure increased by about 50%.
Clemastine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Codeine: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking tasimelteon. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Codeine; Guaifenesin: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking tasimelteon. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking tasimelteon. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking tasimelteon. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Codeine; Promethazine: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking tasimelteon. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
COMT inhibitors: (Moderate) COMT inhibitors should be given cautiously with other agents that cause CNS depression, including tasimelteon, due to the possibility of additive sedation. COMT inhibitors have also been associated with sudden sleep onset during activities of daily living such as driving, which has resulted in accidents in some cases. Prescribers should re-assess patients for drowsiness or sleepiness regularly throughout treatment, especially since events may occur well after the start of treatment. Patients should be advised to avoid driving or other tasks requiring mental alertness until they know how the combination affects them.
Cyclizine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Cyclobenzaprine: (Moderate) Cyclobenzaprine may cause additive CNS depression if used concomitantly with other CNS depressants, such as anxiolytics, sedatives, and hypnotics. Combination therapy can cause additive effects of sedation and dizziness, which can impair the patient's ability to undertake tasks requiring mental alertness. Dosage adjustments of either or both medications may be necessary.
Cyproheptadine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Dabrafenib: (Moderate) Caution is recommended during concurrent use of tasimelteon and dabrafenib. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inducers, such as dabrafenib, may reduce the efficacy of tasimelteon.
Danazol: (Moderate) Caution is recommended during concurrent use of tasimelteon and danazol. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors, such as danazol, may increase exposure to tasimelteon with the potential for adverse reactions.
Darunavir: (Moderate) Caution is recommended during concurrent use of tasimelteon and darunavir. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors, such as darunavir, may increase exposure to tasimelteon with the potential for adverse reactions.
Darunavir; Cobicistat: (Moderate) Caution is recommended during concurrent use of tasimelteon and darunavir. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors, such as darunavir, may increase exposure to tasimelteon with the potential for adverse reactions.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Moderate) Caution is recommended during concurrent use of tasimelteon and darunavir. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors, such as darunavir, may increase exposure to tasimelteon with the potential for adverse reactions.
Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) Concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as ritonavir, should be avoided if possible. Because tasimelteon is partially metabolized via CYP3A4, a large increase in exposure of tasimelteon with the potential for adverse reactions is possible if these drugs are coadministered. During administration of tasimelteon and another potent CYP3A4 inhibitor, tasimelteon exposure increased by about 50%.
Delavirdine: (Major) Concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as delavirdine, should be avoided if possible. Because tasimelteon is partially metabolized via CYP3A4, a large increase in exposure of tasimelteon with the potential for adverse reactions is possible if these drugs are coadministered. During administration of tasimelteon and another potent CYP3A4 inhibitor, tasimelteon exposure increased by about 50%.
Deutetrabenazine: (Moderate) Advise patients that concurrent use of deutetrabenazine and drugs that can cause CNS depression, such as tasimelteon, may have additive effects and worsen drowsiness or sedation.
Dexamethasone: (Moderate) Caution is recommended during concurrent use of tasimelteon and dexamethasone. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inducers, such as dexamethasone, may reduce the efficacy of tasimelteon.
Dexbrompheniramine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Dexbrompheniramine; Pseudoephedrine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Dexchlorpheniramine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Dextromethorphan; Diphenhydramine; Phenylephrine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Difelikefalin: (Moderate) Monitor for dizziness, somnolence, mental status changes, and gait disturbances if concomitant use of difelikefalin with CNS depressants is necessary. Concomitant use may increase the risk for these adverse reactions.
Diltiazem: (Moderate) Caution is recommended during concurrent use of tasimelteon and diltiazem. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors, such as diltiazem, may increase exposure to tasimelteon with the potential for adverse reactions.
Dimenhydrinate: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Diphenhydramine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Diphenhydramine; Ibuprofen: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Diphenhydramine; Naproxen: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Diphenhydramine; Phenylephrine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Dorzolamide; Timolol: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Doxylamine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Doxylamine; Pyridoxine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Dronedarone: (Moderate) Caution is recommended during concurrent use of tasimelteon and dronedarone. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors, such as dronedarone, may increase exposure to tasimelteon with the potential for adverse reactions.
Efavirenz: (Moderate) Caution is recommended during concurrent use of tasimelteon and efavirenz. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors may increase exposure to tasimelteon with the potential for adverse reactions. Because efavirenz may inhibit or induce CYP3A4, the clinical outcome of this combination is unknown.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is recommended during concurrent use of tasimelteon and efavirenz. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors may increase exposure to tasimelteon with the potential for adverse reactions. Because efavirenz may inhibit or induce CYP3A4, the clinical outcome of this combination is unknown.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is recommended during concurrent use of tasimelteon and efavirenz. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors may increase exposure to tasimelteon with the potential for adverse reactions. Because efavirenz may inhibit or induce CYP3A4, the clinical outcome of this combination is unknown.
Elbasvir; Grazoprevir: (Moderate) Administering tasimelteon with elbasvir; grazoprevir may result in elevated tasimelteon plasma concentrations. Tasimelteon is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Enzalutamide: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as enzalutamide, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of tasimelteon with another potent inducer of CYP3A4, tasimelteon exposure decreased by about 90%.
Ergotamine; Caffeine: (Minor) Caffeine is a central nervous system (CNS) stimulant. Patients taking melatonin or the melatonin analogs (ramelteon, tasimelteon) for sleep should avoid caffeine-containing medications, dietary supplements, foods, and beverages close to bedtime. Patients should be encouraged to avoid excessive total daily caffeine intake, as part of proper sleep hygiene, since caffeine intake can interfere with proper sleep.
Erythromycin: (Moderate) Caution is recommended during concurrent use of tasimelteon and erythromycin. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors, such as erythromycin, may increase exposure to tasimelteon with the potential for adverse reactions.
Esketamine: (Moderate) Closely monitor patients receiving esketamine and tasimelteon for sedation and other CNS depressant effects. Instruct patients who receive a dose of esketamine not to drive or engage in other activities requiring alertness until the next day after a restful sleep.
Eslicarbazepine: (Moderate) Caution is recommended during concurrent use of tasimelteon and eslicarbazepine. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inducers, such as eslicarbazepine, may reduce the efficacy of tasimelteon.
Esmolol: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Ethanol: (Major) Advise patients to avoid alcohol consumption while taking tasimelteon. A single dose study indicated a trend towards additive effects of tasimelteon and alcohol on some psychomotor tests.
Ethotoin: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as hydantoins, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of tasimelteon with another potent inducer of CYP3A4, tasimelteon exposure decreased by about 90%.
Etravirine: (Moderate) Caution is recommended during concurrent use of tasimelteon and etravirine. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inducers, such as etravirine, may reduce the efficacy of tasimelteon.
Fenfluramine: (Moderate) Monitor for excessive sedation and somnolence during coadministration of fenfluramine and tasimelteon. Concurrent use may result in additive CNS depression.
Fentanyl: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Fluconazole: (Moderate) Caution is recommended during concurrent use of tasimelteon and fluconazole. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors, such as fluconazole, may increase exposure to tasimelteon with the potential for adverse reactions.
Fluvoxamine: (Major) Concurrent use of tasimelteon and strong inhibitors of CYP1A2, such as fluvoxamine, should be avoided. Because tasimelteon is partially metabolized via CYP1A2, a large increase in exposure of tasimelteon with the potential for adverse reactions is possible if these drugs are coadministered. During administration of fluvoxamine 50 mg/day for 6 days, the AUC and Cmax of tasimelteon increased by 7-fold and 2-fold, respectively.
Food: (Major) Advise patients to avoid cannabis use while taking CNS depressants due to the risk for additive CNS depression and potential for other cognitive adverse reactions.
Fosamprenavir: (Major) Concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as amprenavir or fosamprenavir, should be avoided if possible. Because tasimelteon is partially metabolized via CYP3A4, a large increase in exposure of tasimelteon with the potential for adverse reactions is possible if these drugs are coadministered. During administration of tasimelteon and another potent CYP3A4 inhibitor, tasimelteon exposure increased by about 50%.
Fosphenytoin: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as hydantoins, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of tasimelteon with another potent inducer of CYP3A4, tasimelteon exposure decreased by about 90%.
Gabapentin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of tasimelteon and gabapentin. Concurrent use may result in additive CNS depression.
Givosiran: (Major) Avoid concomitant use of givosiran and tasimelteon due to the risk of increased tasimelteon-related adverse reactions. If use is necessary, consider decreasing the tasimelteon dose. Tasimelteon is a sensitive CYP1A2 substrate. Givosiran may moderately reduce hepatic CYP1A2 enzyme activity because of its pharmacological effects on the hepatic heme biosynthesis pathway.
Guaifenesin; Hydrocodone: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking tasimelteon. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking tasimelteon. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Homatropine; Hydrocodone: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking tasimelteon. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydantoins: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as hydantoins, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of tasimelteon with another potent inducer of CYP3A4, tasimelteon exposure decreased by about 90%.
Hydrocodone: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking tasimelteon. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydrocodone; Ibuprofen: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking tasimelteon. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydrocodone; Pseudoephedrine: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Avoid prescribing opioid cough medications in patients taking tasimelteon. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydromorphone: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Hydroxyzine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Ibuprofen; Oxycodone: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Imatinib: (Moderate) Caution is recommended during concurrent use of tasimelteon and imatinib, STI-571. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors, such as imatinib, may increase exposure to tasimelteon with the potential for adverse reactions.
Indinavir: (Major) Concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as indinavir, should be avoided if possible. Because tasimelteon is partially metabolized via CYP3A4, a large increase in exposure of tasimelteon with the potential for adverse reactions is possible if these drugs are coadministered. During administration of tasimelteon and another potent CYP3A4 inhibitor, tasimelteon exposure increased by about 50%.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with tasimelteon may result in increased serum concentrations of tasimelteon. Tasimelteon is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as rifampin, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of rifampin 600 mg/day for 11 days, the exposure of tasimelteon decreased by about 90%. Rifampin also induces CYP1A2, a secondary metabolic pathway of tasimelteon.
Isoniazid, INH; Rifampin: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as rifampin, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of rifampin 600 mg/day for 11 days, the exposure of tasimelteon decreased by about 90%. Rifampin also induces CYP1A2, a secondary metabolic pathway of tasimelteon.
Itraconazole: (Major) Concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as itraconazole, should be avoided if possible. Because tasimelteon is partially metabolized via CYP3A4, a large increase in exposure of tasimelteon with the potential for adverse reactions is possible if these drugs are coadministered. During administration of tasimelteon and another potent CYP3A4 inhibitor, tasimelteon exposure increased by about 50%.
Ketoconazole: (Moderate) Avoid concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as ketoconazole, if possible. Tasimelteon is partially metabolized via CYP3A4, and an increase in exposure of tasimelteon with the potential for adverse reactions is possible if a strong CYP3A4 inhibitor is coadministered. During administration of ketoconazole 40 mg/day for 5 days, tasimelteon exposure increased by about 50%.
Labetalol: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as clarithromycin, should be avoided if possible. Because tasimelteon is partially metabolized via CYP3A4, a large increase in exposure of tasimelteon with the potential for adverse reactions is possible if these drugs are coadministered. During administration of tasimelteon and another potent CYP3A4 inhibitor, tasimelteon exposure increased by about 50%.
Lasmiditan: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lasmiditan and tasimelteon. Concurrent use may result in additive CNS depression.
Lemborexant: (Major) The use of lemborexant with other hypnotic drugs, such as tasimelteon, is not recommended. Additive sedative, CNS depressant effects, impairment, and effects on mood and behaviors, including sleep-related behaviors, may occur.
Letermovir: (Moderate) An increase in the plasma concentration of tasimelteon may occur during concurrent administration with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Tasimelteon is partially metabolized by CYP3A4. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates is similar to a strong CYP3A4 inhibitor. In a drug interaction study, administration of tasimelteon with another strong CYP3A4 inhibitor increased tasimelteon exposure by approximately 50%.
Levobetaxolol: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Levobunolol: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Levocetirizine: (Moderate) Concurrent use of cetirizine/levocetirizine with tasimelteon should generally be avoided. Coadministration may increase the risk of CNS depressant-related side effects. If concurrent use is necessary, monitor for excessive sedation and somnolence.
Levoketoconazole: (Moderate) Avoid concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as ketoconazole, if possible. Tasimelteon is partially metabolized via CYP3A4, and an increase in exposure of tasimelteon with the potential for adverse reactions is possible if a strong CYP3A4 inhibitor is coadministered. During administration of ketoconazole 40 mg/day for 5 days, tasimelteon exposure increased by about 50%.
Levorphanol: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Lofexidine: (Moderate) Monitor for excessive sedation during coadministration of lofexidine and tasimelteon. Lofexidine can potentiate the effects of CNS depressants.
Lopinavir; Ritonavir: (Major) Concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as ritonavir, should be avoided if possible. Because tasimelteon is partially metabolized via CYP3A4, a large increase in exposure of tasimelteon with the potential for adverse reactions is possible if these drugs are coadministered. During administration of tasimelteon and another potent CYP3A4 inhibitor, tasimelteon exposure increased by about 50%.
Lumacaftor; Ivacaftor: (Major) Lumacaftor; ivacaftor may reduce the efficacy of tasimelteon by significantly decreasing its systemic exposure; avoid concomitant use. Tasimelteon is a CYP3A substrate, and lumacaftor is a strong CYP3A inducer.
Lumateperone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of lumateperone and tasimelteon. Concurrent use may result in additive CNS depression.
Lurasidone: (Moderate) Drugs that can cause CNS depression, if used concomitantly with atypical antipsychotics, can increase both the frequency and the intensity of adverse effects such as drowsiness, sedation, and dizziness.
Meclizine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Melatonin: (Major) Because of pharmacologic similarities in action as melatonin-receptor agonists, tasimelteon should likely not be coadministered with melatonin. The actions would be expected to be duplicative, and might result in additive side effects. In a clinical trial, there was clear evidence for a transitory pharmacodynamic interaction between melatonin and another hypnotic agent one hour following co-dosing. Concomitant administration resulted in increased impairment of attention, memory and coordination compared to the hypnotic agent alone. Use of more than one agent for hypnotic purposes may increase the risk for over-sedation, CNS effects, or sleep-related behaviors. Be alert for unusual changes in moods or behaviors. Patients should be advised to avoid dietary supplements containing melatonin.
Meperidine: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Meperidine; Promethazine: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Methadone: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Methohexital: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as barbiturates or primidone, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of tasimelteon with another potent inducer of CYP3A4, tasimelteon exposure decreased by about 90%. Barbiturates also induce CYP1A2, a secondary metabolic pathway of tasimelteon.
Metoprolol: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Mexiletine: (Moderate) Caution is recommended during concurrent use of tasimelteon and mexiletine. Because tasimelteon is partially metabolized via CYP1A2, use with CYP1A2 inhibitors, such as mexiletine, may increase exposure to tasimelteon and the potential for adverse reactions.
Mitotane: (Major) Avoid the concomitant use of mitotane with tasimelteon due to decreased tasimelteon exposure and possible decreases in efficacy. Mitotane is a strong CYP3A4 inducer and tasimelteon is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of tasimelteon. During administration of tasimelteon with another potent inducer of CYP3A4, tasimelteon exposure decreased by about 90%.
Modafinil: (Moderate) Caution is recommended during concurrent use of tasimelteon and modafinil or armodafinil. Because tasimelteon is metabolized via CYP3A4 and CYP1A2, inducers of these isoenzymes, such as modafinil and armodafinil, may reduce the efficacy of tasimelteon.
Morphine: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Morphine; Naltrexone: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Nabilone: (Moderate) Monitor for excessive sedation and somnolence during coadministration of nabilone and tasimelteon. Concurrent use may result in additive CNS depression.
Nadolol: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Nebivolol: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Nebivolol; Valsartan: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Nefazodone: (Major) Concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as nefazodone, should be avoided if possible. Because tasimelteon is partially metabolized via CYP3A4, a large increase in exposure of tasimelteon with the potential for adverse reactions is possible if these drugs are coadministered. During administration of tasimelteon and another potent CYP3A4 inhibitor, tasimelteon exposure increased by about 50%.
Nelfinavir: (Moderate) Caution is recommended during concurrent use of tasimelteon and nelfinavir. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors, such as nelfinavir, may increase exposure to tasimelteon with the potential for adverse reactions.
Nilotinib: (Moderate) Caution is recommended during concurrent use of tasimelteon and nilotinib. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors, such as nilotinib, may increase exposure to tasimelteon with the potential for adverse reactions.
Nirmatrelvir; Ritonavir: (Major) Concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as ritonavir, should be avoided if possible. Because tasimelteon is partially metabolized via CYP3A4, a large increase in exposure of tasimelteon with the potential for adverse reactions is possible if these drugs are coadministered. During administration of tasimelteon and another potent CYP3A4 inhibitor, tasimelteon exposure increased by about 50%.
Obeticholic Acid: (Moderate) Obeticholic acid may increase the exposure to concomitant drugs that are CYP1A2 substrates, such as tasimelteon. Therapeutic monitoring is recommended with coadministration.
Oliceridine: (Moderate) Concomitant use of oliceridine with tasimelteon may cause excessive sedation and somnolence. Limit the use of oliceridine with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect.
Ombitasvir; Paritaprevir; Ritonavir: (Major) Concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as ritonavir, should be avoided if possible. Because tasimelteon is partially metabolized via CYP3A4, a large increase in exposure of tasimelteon with the potential for adverse reactions is possible if these drugs are coadministered. During administration of tasimelteon and another potent CYP3A4 inhibitor, tasimelteon exposure increased by about 50%.
Omeprazole; Amoxicillin; Rifabutin: (Moderate) Caution is recommended during concurrent use of tasimelteon and rifabutin. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inducers, such as rifabutin, may reduce the efficacy of tasimelteon.
Oxycodone: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Oxymorphone: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Penbutolol: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Pentobarbital: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as barbiturates or primidone, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of tasimelteon with another potent inducer of CYP3A4, tasimelteon exposure decreased by about 90%. Barbiturates also induce CYP1A2, a secondary metabolic pathway of tasimelteon.
Phenobarbital: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as barbiturates or primidone, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of tasimelteon with another potent inducer of CYP3A4, tasimelteon exposure decreased by about 90%. Barbiturates also induce CYP1A2, a secondary metabolic pathway of tasimelteon.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as barbiturates or primidone, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of tasimelteon with another potent inducer of CYP3A4, tasimelteon exposure decreased by about 90%. Barbiturates also induce CYP1A2, a secondary metabolic pathway of tasimelteon.
Phenytoin: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as hydantoins, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of tasimelteon with another potent inducer of CYP3A4, tasimelteon exposure decreased by about 90%.
Pindolol: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Posaconazole: (Major) Concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as posaconazole, should be avoided if possible. Because tasimelteon is partially metabolized via CYP3A4, a large increase in exposure of tasimelteon with the potential for adverse reactions is possible if these drugs are coadministered. During administration of tasimelteon and another potent CYP3A4 inhibitor, tasimelteon exposure increased by about 50%.
Pregabalin: (Moderate) Monitor for excessive sedation and somnolence during coadministration of tasimelteon and pregabalin. Concurrent use may result in additive CNS depression.
Primidone: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as barbiturates or primidone, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of tasimelteon with another potent inducer of CYP3A4, tasimelteon exposure decreased by about 90%. Barbiturates also induce CYP1A2, a secondary metabolic pathway of tasimelteon.
Propranolol: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Pseudoephedrine; Triprolidine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Pyrilamine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Ramelteon: (Contraindicated) Because of pharmacologic similarities in action as melatonin-receptor agonists, ramelteon should not be coadministered with tasimelteon. The actions would be expected to be duplicative, and might result in additive side effects, such as somnolence, headache, unusual behaviors or moods, memory impairment, or balance and coordination issues.
Remifentanil: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Remimazolam: (Moderate) The sedative effect of remimazolam can be accentuated by tasimelteon. Titrate the dose of remimazolam to the desired clinical response and continuously monitor sedated patients for hypotension, airway obstruction, hypoventilation, apnea, and oxygen desaturation.
Rifabutin: (Moderate) Caution is recommended during concurrent use of tasimelteon and rifabutin. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inducers, such as rifabutin, may reduce the efficacy of tasimelteon.
Rifampin: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as rifampin, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of rifampin 600 mg/day for 11 days, the exposure of tasimelteon decreased by about 90%. Rifampin also induces CYP1A2, a secondary metabolic pathway of tasimelteon.
Rifapentine: (Major) Avoid coadministration of tasimelteon with rifapentine due to the potential for a large decrease in tasimelteon exposure resulting in reduced efficacy. Tasimelteon is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. Coadministration with another strong CYP3A4 inducer decreased tasimelteon exposure by about 90%.
Ritonavir: (Major) Concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as ritonavir, should be avoided if possible. Because tasimelteon is partially metabolized via CYP3A4, a large increase in exposure of tasimelteon with the potential for adverse reactions is possible if these drugs are coadministered. During administration of tasimelteon and another potent CYP3A4 inhibitor, tasimelteon exposure increased by about 50%.
Safinamide: (Moderate) Dopaminergic medications, including safinamide, may cause a sudden onset of somnolence which sometimes has resulted in motor vehicle accidents. Patients may not perceive warning signs, such as excessive drowsiness, or they may report feeling alert immediately prior to the event. Because of possible additive effects, advise patients about the potential for increased somnolence during concurrent use of safinamide with other sedating medications, such as tasimelteon.
Saquinavir: (Moderate) Caution is recommended during concurrent use of tasimelteon and saquinavir. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors, such as saquinavir, may increase exposure to tasimelteon with the potential for adverse reactions.
Secobarbital: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as barbiturates or primidone, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of tasimelteon with another potent inducer of CYP3A4, tasimelteon exposure decreased by about 90%. Barbiturates also induce CYP1A2, a secondary metabolic pathway of tasimelteon.
Sedating H1-blockers: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Sotalol: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
St. John's Wort, Hypericum perforatum: (Major) Concurrent use of tasimelteon and strong inducers of CYP3A4, such as St. John's Wort, hypericum perforatum, should be avoided. Because tasimelteon is partially metabolized via CYP3A4, a large decrease in exposure is possible with the potential for reduced efficacy. During administration of tasimelteon with another potent inducer of CYP3A4, tasimelteon exposure decreased by about 90%.
Stiripentol: (Moderate) Consider a dose adjustment of tasimelton when coadministered with stiripentol. Coadministration may alter plasma concentrations of tasimelton resulting in an increased risk of adverse reactions and/or decreased efficacy. Additive somnolence and sedation may occur. Tasimelton is a sensitive CYP1A2 substrate. In vitro data predicts inhibition or induction of CYP1A2 by stiripentol potentially resulting in clinically significant interactions.
Sufentanil: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Suvorexant: (Major) The use of suvorexant with other hypnotic drugs, such as tasimelteon, is not recommended. Additive sedative, CNS depressant effects, impairment, and effects on mood and behaviors, including sleep-related behaviors, may occur.
Tapentadol: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Timolol: (Moderate) Advise patients to administer the beta-blocker in the morning if tasimelteon is used concomitantly. Nighttime administration of a beta-blocker may reduce the efficacy of tasimelteon by decreasing the production of melatonin via inhibition of beta1 receptors.
Tipranavir: (Major) Concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as tipranavir, should be avoided if possible. Because tasimelteon is partially metabolized via CYP3A4, a large increase in exposure of tasimelteon with the potential for adverse reactions is possible if these drugs are coadministered. During administration of tasimelteon and another potent CYP3A4 inhibitor, tasimelteon exposure increased by about 50%.
Tobacco: (Major) Advise patients to avoid smoking tobacco while taking tasimelteon. Due to partial metabolism of tasimelteon by CYP1A2, drug exposure is decreased by about 40% in smokers compared to non-smokers. Patients should be advised of the potential for reduced efficacy due to tobacco use.
Tramadol: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Tramadol; Acetaminophen: (Moderate) Concomitant use of opioid agonists with tasimelteon may cause excessive sedation and somnolence. Limit the use of opioid pain medications with tasimelteon to only patients for whom alternative treatment options are inadequate. If concurrent use is necessary, use the lowest effective doses and minimum treatment durations needed to achieve the desired clinical effect. Educate patients about the risks and symptoms of excessive CNS depression.
Trandolapril; Verapamil: (Moderate) Caution is recommended during concurrent use of tasimelteon and verapamil. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors, such as verapamil, may increase exposure to tasimelteon with the potential for adverse reactions.
Trazodone: (Moderate) CNS depressants should be used cautiously in patients receiving trazodone because of additive CNS depressant effects, including possible respiratory depression or hypotension. A dose reduction of one or both drugs may be warranted.
Triprolidine: (Moderate) Because sedating H1-blockers cause sedation, an enhanced CNS depressant effect may occur when it is combined with other CNS depressants including anxiolytics, sedatives, and hypnotics, such as tasimelteon.
Vemurafenib: (Moderate) Caution is recommended during concurrent use of tasimelteon and vemurafenib. Concurrent use of these agents may have variable effects on tasimelteon exposure. Vemurafenib has inhibitory effects on CYP1A2 and inducing effects on CYP3A4, which are two metabolic pathways of tasimelteon.
Verapamil: (Moderate) Caution is recommended during concurrent use of tasimelteon and verapamil. Because tasimelteon is partially metabolized via CYP3A4, use with CYP3A4 inhibitors, such as verapamil, may increase exposure to tasimelteon with the potential for adverse reactions.
Viloxazine: (Contraindicated) Concomitant use of viloxazine and tasimelteon is contraindicated due to the increased risk for tasimelteon-related adverse effects and exposure. Tasimelteon is a CYP1A2 substrate and viloxazine is a strong CYP1A2 inhibitor. Coadministration with another strong CYP1A2 inhibitor increased tasimelteon exposure by 7-fold.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as clarithromycin, should be avoided if possible. Because tasimelteon is partially metabolized via CYP3A4, a large increase in exposure of tasimelteon with the potential for adverse reactions is possible if these drugs are coadministered. During administration of tasimelteon and another potent CYP3A4 inhibitor, tasimelteon exposure increased by about 50%.
Voriconazole: (Major) Concurrent use of tasimelteon and strong inhibitors of CYP3A4, such as voriconazole, should be avoided if possible. Because tasimelteon is partially metabolized via CYP3A4, a large increase in exposure of tasimelteon with the potential for adverse reactions is possible if these drugs are coadministered. During administration of tasimelteon and another potent CYP3A4 inhibitor, tasimelteon exposure increased by about 50%.
Zileuton: (Moderate) Caution is recommended during concurrent use of tasimelteon and zileuton. Because tasimelteon is partially metabolized via CYP1A2, use with a CYP1A2 inhibitor, such as zileuton, may increase exposure to tasimelteon and the potential for adverse reactions.

PREGNANCY AND LACTATION

Tasimelteon should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Available postmarketing case reports with use of tasimelteon in pregnant women are not sufficient to evaluate drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. In pregnant rats, no embryofetal developmental toxicity was observed at exposures of up to 50 mg/kg/day (the no-effect dose), or approximately 25 times the human exposure at the maximum recommended human dose (MRHD) of 20 mg/day. Oral administration of tasimelteon at 50, 150, or 450 mg/kg/day to rats throughout organogenesis resulted in persistent reductions in body weight, delayed sexual maturation, and physical development, and neurobehavioral impairment in offspring at the highest dose tested which is approximately 220 times the MRHD based on body surface area. Reduced body weight in offspring was also observed at the mid-dose. It is not known what effect tasimelteon would have during labor or obstetric delivery.

There are no data on the presence of tasimelteon in human milk, the effects on the breastfed infant, or the effects on milk production. Caution is advisable when administering tasimelteon to a woman who is breast-feeding an infant. Consider the developmental and health benefits of breast-feeding along with the mother's clinical need for tasimelteon and any potential adverse effects on the breastfed infant from tasimelteon or the underlying maternal condition. 

MECHANISM OF ACTION

Tasimelteon is a melatonin receptor agonist. Tasimelteon is an agonist at MT1 and MT2, which are believed to be involved in the promotion of sleep and the maintenance of the normal circadian rhythm (shift between day and night).

PHARMACOKINETICS

Tasimelteon is administered orally. Apparent Vd at steady state is approximately 59 to 126 L. Approximately 90% is protein bound. Metabolism occurs primarily through oxidation at multiple sites and oxidative dealkylation resulting in opening of the dihydrofuran ring followed by further oxidation to a carboxylic acid. The major isoenzymes involved in the metabolism of tasimelteon are CYP1A2 and CYP3A4. Phenolic glucuronidation is the major phase II metabolic route. The major metabolites of tasimelteon have 13-fold or less activity at melatonin receptors than the parent compound. The mean elimination half-life of tasimelteon is 1.3 hours +/- 0.4 hours. The mean elimination half-lives of the primary metabolites range from 1.3 hours +/- 0.5 to 3.7 hours +/- 2.2 hours. Approximately 4% of a dose is excreted in the feces and 80% in the urine. Less than 1% of a dose is excreted in urine as the parent compound.
 
Affected cytochrome P450 isoenzymes and drug transporters: CYP1A2 and CYP3A4
No drug interactions have been identified in vitro with inducers or inhibitors of CYP1A1, CYP1A2, CYP2B6, CYP2C9/2C19, CYP2E1, CYP2D6, P-glycoprotein, OATP1B1, OATP1B3, OCT2, OAT1, or OAT3. Drugs that inhibit CYP1A2 and CYP3A4 are expected to alter the metabolism of tasimelteon.