CYP3A4 metabolism. Modify Therapy/Monitor Closely.rifabutinMonitor Closely (1)rifabutin will decrease the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inducers may decrease suvorexant efficacy; if increased suvorexant dose required, do not exceed 20 mg/dayrifampinMonitor Closely (1)rifampin will decrease the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inducers may decrease suvorexant efficacy; if increased suvorexant dose required, do not exceed 20 mg/dayrifapentineMonitor Closely (1)rifapentine will decrease the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inducers may decrease suvorexant efficacy; if increased suvorexant dose required, do not exceed 20 mg/dayrimegepantSerious - Use Alternative (1)suvorexant will increase the level or effect of rimegepant by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug.ritonavirSerious - Use Alternative (1)ritonavir increases levels of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Suvorexant not recommended with use of strong CYP3A4 inhibitors.rucaparibMonitor Closely (1)rucaparib will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Adjust dosage of CYP3A4 substrates, if clinically indicated.saquinavirSerious - Use Alternative (1)saquinavir increases levels of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Suvorexant not recommended with use of strong CYP3A4 inhibitors.secobarbitalMonitor Closely (2)secobarbital will decrease the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. suvorexant and secobarbital both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessaryselinexorSerious - Use Alternative (1)selinexor, suvorexant. unspecified interaction mechanism. Avoid or Use Alternate Drug. Patients treated with selinexor may experience neurological toxicities. Avoid taking selinexor with other medications that may cause dizziness or confusion.sertralineMonitor Closely (1)sertraline will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitorsSt John's WortMonitor Closely (1)St John's Wort will decrease the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Strong CYP3A4 inducers may decrease suvorexant efficacy; if increased suvorexant dose required, do not exceed 20 mg/daystiripentolMonitor Closely (2)stiripentol, suvorexant. Either increases effects of the other by sedation. Use Caution/Monitor. Concomitant use stiripentol with other CNS depressants, including alcohol, may increase the risk of sedation and somnolence. stiripentol, suvorexant. affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Stiripentol is a CYP3A4 inhibitor and inducer. Monitor CYP3A4 substrates coadministered with stiripentol for increased or decreased effects. CYP3A4 substrates may require dosage adjustment.sufentanilMonitor Closely (1)suvorexant and sufentanil both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessarysufentanil SLMonitor Closely (1)suvorexant and sufentanil SL both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessarySerious - Use Alternative (1)sufentanil SL, suvorexant. Either increases toxicity of the other by pharmacodynamic synergism. Avoid or Use Alternate Drug. Coadministration may result in hypotension, profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs in patients for whom other treatment options are inadequate. Limit dosages and durations to the minimum required. Monitor closely for signs of respiratory depression and sedation.tapentadolMonitor Closely (1)suvorexant and tapentadol both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessarytazemetostatMonitor Closely (1)tazemetostat will decrease the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor.tecovirimatMonitor Closely (1)tecovirimat will decrease the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Tecovirimat is a weak CYP3A4 inducer. Monitor sensitive CYP3A4 substrates for effectiveness if coadministered.tetracyclineMonitor Closely (1)tetracycline will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitorsticagrelorMonitor Closely (1)ticagrelor will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitorstipranavirSerious - Use Alternative (1)tipranavir increases levels of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Suvorexant not recommended with use of strong CYP3A4 inhibitors.tramadolMonitor Closely (1)suvorexant and tramadol both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessarytrimipramineMonitor Closely (1)suvorexant and trimipramine both increase sedation. Modify Therapy/Monitor Closely. Dosage adjustments of suvorexant and concomitant CNS depressants may be necessarytucatinibSerious - Use Alternative (1)tucatinib will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Avoid concomitant use of tucatinib with CYP3A substrates, where minimal concentration changes may lead to serious or life-threatening toxicities. If unavoidable, reduce CYP3A substrate dose according to product labeling.valerianSerious - Use Alternative (1)valerian and suvorexant both increase sedation. Avoid or Use Alternate Drug.venetoclaxSerious - Use Alternative (1)suvorexant will increase the level or effect of venetoclax by P-glycoprotein (MDR1) efflux transporter. Avoid or Use Alternate Drug. If a P-gp inhibitor must be used, reduce the venetoclax dose by at least 50%. Monitor more closely for signs of venetoclax toxicities.verapamilMonitor Closely (1)verapamil will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitorsvoriconazoleSerious - Use Alternative (1)voriconazole increases levels of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Suvorexant not recommended with use of strong CYP3A4 inhibitors.voxelotorSerious - Use Alternative (1)voxelotor will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Voxelotor increases systemic exposure of sensitive CYP3A4 substrates. Avoid coadministration with sensitive CYP3A4 substrates with a narrow therapeutic index. Consider dose reduction of the sensitive CYP3A4 substrate(s) if unable to avoid.zileutonMonitor Closely (1)zileuton will increase the level or effect of suvorexant by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Modify Therapy/Monitor Closely. Decrease suvorexant starting dose to 5 mg HS if coadministered with moderate CYP3A4 inhibitors 1-10% Somnolence, females (8%) Somnolence (7%) Headache (7%) Somnolence, males (3%) Dizziness (3%) Abnormal dreams (2%) Cough (2%) Diarrhea (2%) Dry mouth (2%) Upper respiratory tract infection (2%) Postmarketing Reports Cardiac disorders: Palpitations, tachycardia Nervous system disorders: Psychomotor hyperactivity Psychiatric disorders: Anxiety Skin and subcutaneous tissue disorders: Pruritus Gastrointestinal disorders: Nausea, vomiting Contraindications Narcolepsy Cautions Can impair daytime wakefulness; CNS depressant effects can last for up to several days after discontinuation Can impair driving skills and may increase the risk of falling asleep while driving Patients should not use suvorexant if they drank alcohol that evening or before bed; coadministration with other CNS depressants (eg, benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression Dosage adjustments of suvorexant and concomitant CNS depressants may be necessary when administered together because of potentially additive effects Use with other drugs to treat insomnia is not recommended Risk of next-day impairment, including impaired driving, is increased if taken with less than a full night of sleep remaining, if a higher than the recommended dose is taken, if coadministered with other CNS depressants, or if coadministered with other drugs that increase suvorexant blood levels Caution patients taking 20 mg to refrain from next-day driving and other activities requiring full mental alertness Reevaluate patients for comorbid conditions if insomnia persists after 7-10 days of treatment Cognitive and behavioral changes (eg, amnesia, anxiety, hallucinations, and other neuropsychiatric symptoms) reported with hypnotics; “sleep driving” and other complex behaviors (eg, preparing and eating food, making phone calls, or having sex), with amnesia for the event, have been reported; discontinue therapy immediately if a patient experiences a complex sleep behavior The use of alcohol and other CNS depressants may increase the risk of cognitive changes listed above; discontinuation should be strongly considered Dose-dependent increase in suicidal ideation was observed in patients taking suvorexant, as assessed by questionnaire; immediately evaluate patients with suicidal ideation or any new-onset behavioral changes; worsening depression or suicidal thinking, thoughts, and actions have been reported with the use of sedative-hypnotic Consider effect on respiratory function Risk of sleep paralysis, hypnagogic/hypnopompic hallucinations, and cataplexy-like symptoms increases with increasing doses Not recommended for patients with severe hepatic impairment or those taking a strong CYP3A inhibitor Pregnancy Available data from postmarketing reports in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes Animal data In animal reproduction studies, oral administration to pregnant rats and rabbits during period of organogenesis decreased maternal body weight and/or weight gain at doses ≥ 30 and 28 times maximum recommended human dose (MRHD) of 20 mg based on AUC in the rat and rabbit, respectively Treatment caused decreased fetal weight at doses ≥ 86 times MRHD based on AUC in rat and did not cause significant fetal toxicity at doses up to 28 times MRHD based on AUC in the rabbit The no observed adverse effect levels (NOAELs) for fetal toxicity are 25 and 28 times MRHD based on AUC in rat and rabbit, respectively Oral administration to pregnant rats during pregnancy and lactation caused decreased maternal and pup body weight or weight gain at approximately 48 times the MRHD based on AUC; the NOAEL for development toxicity in rat is 25 times the MRHD based on AUC Lactation There are no data on presence of drug in human milk, effects on breastfed infant or on milk production; drug and metabolite are present in rat milk; when drug is present in animal milk, it is likely that the drug will be present in human milk Infants exposed to drug through breastmilk should be monitored for excessive sedation; the developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for drug and any potential adverse effects on breastfed infant from drug or from underlying maternal conditionPregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Orexin receptor antagonist; orexin, also called hypocretin, is a neurotransmitter that regulates arousal, wakefulness, and appetite Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R is thought to suppress wake drive Absorption Bioavailability: 82% Peak plasma time: 2 hr (range 30 min to 6 hr) Taking after a high-fat meal delays peak concentration by ~1.5 hr Distribution Protein bound: >99% to human serum albumin and α1-acid glycoprotein Not preferentially distribute into RBCs Vd: 49 L Metabolism Mainly eliminated by metabolism, primarily by CYP3A with a minor contribution from CYP2C19 Metabolite: hydroxy-suvorexant (not active) Elimination Half-life: ~12 hr Excretion: 66% feces; 23% urine Oral Administration May take with or without food; however, for faster sleep onset, do not administer soon after a meal because food will delay the onset of action If alcohol consumed in the evening or before bed, do not take suvorexant BRAND FORM. UNIT PRICE PILL IMAGE Belsomra oral- 20 mg tabletBelsomra oral- 15 mg tabletBelsomra oral- 10 mg tabletCopyright © 2010 First DataBank, Inc.Print Patient Educationsuvorexant oral SUVOREXANT - ORAL (SOO-voe-REX-ant) COMMON BRAND NAME(S): Belsomra USES: This medication is used to treat a certain sleep problem (insomnia). It may help you fall asleep and stay asleep longer, so you can get a better night's rest. Suvorexant belongs to a class of drugs known as sedative-hypnotics.If your insomnia continues for longer than 7 to 10 days after starting treatment, talk to your doctor to see if you need other treatment. HOW TO USE: Read the Medication Guide provided by your pharmacist before you start taking suvorexant and each time you get a refill. If you have any questions, ask your doctor or pharmacist.Take suvorexant by mouth as directed by your doctor, usually 30 minutes before you get into bed. This medication can be taken with or without food, but it