1) COMMON: Somnolence was the most common adverse event. At doses of 15 or 20 mg, somnolence was more likely to occur in females compared to males. Women were also twice as likely as men to experience the following adverse events: headache, dry mouth, abnormal dreams, cough and upper respiratory tract infections. OTHER: Dizziness and diarrhea have also been reported.
2) SERIOUS EVENTS: The CNS depressant effects of suvorexant may impair daytime wakefulness, driving skills and may increase the risk of falling asleep while driving. Coadministration with other CNS depressants (eg, benzodiazepines, opioids, alcohol, tricyclic antidepressants) can increase the risk of CNS depression. Abnormal thinking and behavioral changes (eg, amnesia, anxiety, hallucinations) have developed in patients using hypnotics like suvorexant. In clinical studies, a dose-dependent increase in suicidal ideation has been self-reported in patients receiving suvorexant. Sleep paralysis, hypnagogic/hypnopompic hallucinations, and a cataplexy-like syndrome may occur in patients prescribed suvorexant.
3) DRUG INTERACTIONS: Concurrent use of suvorexant with strong CYP3A inhibitors (eg, ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin, and conivaptan) is not recommended because it can increase exposure to suvorexant and increase the risk of adverse events. In patients taking moderate CYP3A inhibitors (eg, amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice, imatinib and verapamil), suvorexant should be reduced to 5 mg daily; the dose may be increased to 10 mg daily, if needed. Concurrent administration of suvorexant with alcohol can produce an additive effect on psychomotor impairment.

1) OVERDOSE: Overdose effects are anticipated to be an extension of adverse effects following therapeutic use.

1) Treatment is symptomatic and supportive. Monitor mental status and vital signs. Correct any significant fluid and/or electrolyte abnormalities in patients with severe diarrhea.

1) Treatment is symptomatic and supportive. Monitor mental status and vital signs. Assess airway, monitor pulse oximetry, and ensure adequate ventilation in patients with a severe intoxication or a mixed ingestion (ie, other CNS depressants, alcohol).

1) PREHOSPITAL: Prehospital gastrointestinal decontamination is generally not recommended because of the potential for somnolence and loss of airway protection.
2) HOSPITAL: In general, decontamination is not indicated following a minor exposure, but may be considered for a large overdose that presents early. Consider activated charcoal following a recent significant exposure; administer activated charcoal if the patient is awake and cooperative, not vomiting and the airway is protected.

1) Monitor respiratory and CNS function. Assess airway and monitor pulse oximetry following a significant exposure. Although not anticipated to be necessary following a minor or moderate exposure, ensure adequate ventilation and perform endotracheal intubation in patients with severe intoxication (ie, profound somnolence, coma, respiratory depression).

1) None.

1) Suvorexant is highly protein bound (greater than 99%) and has a volume of distribution of approximately 49 L; therefore, hemodialysis is UNLIKELY to be effective.

1) HOME CRITERIA: An asymptomatic adult (other than mild drowsiness) with an inadvertent ingestion of 1 to 2 extra doses may be monitored at home.
2) OBSERVATION CRITERIA: All patients with deliberate ingestions and symptomatic patients should be sent to a health care facility for observation for at least 12 to 18 hours and/or until clinically improved. Children with an unintentional ingestion should be evaluated in a healthcare facility.
3) ADMISSION CRITERIA: Patients with significant, persistent central nervous system toxicity should be admitted. Patients with coma or respiratory depression should be admitted to an intensive care setting.
4) CONSULT CRITERIA: Consult a poison center or medical toxicologist for assistance in managing a patient with severe toxicity (ie, coma, respiratory depression) or in whom the diagnosis is not clear.

1) Consider the possible ingestion of other CNS depressants (eg, benzodiazepines, opioids, tricyclic antidepressants, alcohol) when managing a suspected overdose.

1) Suvorexant exposure appears to increase in a non-dose proportional manner over the range of 10 to 80 mg because of a decrease in absorption at higher doses. Peak concentrations occur at a median Tmax of 2 hours (range, 30 minutes to 6 hours). Exposure is higher in females than males. In women, the AUC and Cmax are increased by 17% and 9% respectively, following a 40 mg dose. Dose adjustment based on gender only is not indicated. The mean volume of distribution is approximately 49 liters. It is extensively bound (greater than 99%) to human plasma proteins. Suvorexant binds to both human serum albumin and alpha 1-acid glycoprotein. It is mainly eliminated by metabolism, primarily by CYP3A. Elimination is primarily through the feces (66%) and to a lesser extent the urine (23%). The mean t(1/2) is approximately 12 hours.

1) Other chemicals or drugs that can produce somnolence or a decrease in CNS and/or respiratory function.

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) WITH THERAPEUTIC USE

1) Rabbits administered up to 325 mg/kg showed no apparent teratogenic effects. However, premature sacrifice of pregnant rabbits occurred at doses of 325 mg/kg due to excessive toxicity (Prod Info BELSOMRA(R) oral tablets, 2014a).

1) Suvorexant is classified as pregnancy category C (Prod Info BELSOMRA(R) oral tablets, 2014a).
2) There are no adequate and well-controlled studies of suvorexant in pregnant women. Animal studies showed decreased fetal body weights in rats, but no teratogenic effects in rabbits. Due to the lack of human safety information, suvorexant should be used in pregnant women only if the potential benefit outweighs the potential risk to the fetus (Prod Info BELSOMRA(R) oral tablets, 2014a).

1) RATS: Animal studies in pregnant rats, administered suvorexant doses up to 1000 mg/kg, showed decreased fetal body weights following doses greater than 80 mg/kg. Plasma exposures at the no-effect dose were approximately 25 times that of humans taking the maximum recommended dose of 20 mg/day (Prod Info BELSOMRA(R) oral tablets, 2014a).

1) It is unknown whether suvorexant is excreted into human milk. Until additional data are available, caution should be exercised with its use in women who are nursing (Prod Info BELSOMRA(R) oral tablets, 2014a).

1) Suvorexant and a hydroxyl-suvorexant metabolite were excreted in rat milk at concentrations higher (9 and 1.5 times, respectively) than maternal plasma concentrations (Prod Info BELSOMRA(R) oral tablets, 2014a).

1) In two studies, male and female rats were treated with suvorexant both prior to and during mating and continued in females up to gestation day 7. A decrease in live fetuses were reported at the highest dose tested (1200 or 325 mg/kg) in both males and females mated with untreated animals, due to increases in peri-implantation loss and resorptions. The no effect dose for adverse effects on fertility in both males and females were 20 times that in humans at the maximum recommended human dose (Prod Info BELSOMRA(R) oral tablets, 2014a).

1) Routine laboratory studies are not needed unless otherwise clinically indicated.
2) Plasma concentrations are not readily available or clinically useful in the management of overdose.

1) Continuously monitor pulse oximetry and obtain blood gases as needed in patients with evidence of CNS and/or respiratory depression. Other causes of CNS depression (eg, benzodiazepines, opioids, tricyclic antidepressants, alcohol) should be ruled out if the diagnosis is not clear or the patient presents with severe intoxication.

A) Patients with significant, persistent central nervous system toxicity should be admitted. Patients with coma or respiratory depression should be admitted to an intensive care setting.

A) An asymptomatic adult (other than mild drowsiness) with an inadvertent ingestion of 1 to 2 extra doses may be monitored at home.

A) Consult a poison center or medical toxicologist for assistance in managing a patient with severe toxicity (ie, coma, respiratory depression) or in whom the diagnosis is not clear.

A) All patients with deliberate ingestions and symptomatic patients should be sent to a health care facility for observation for at least 12 to 18 hours and/or until clinically improved. Children with an unintentional ingestion should be evaluated in a healthcare facility.

1) In general, decontamination is not indicated following a minor exposure, but may be considered for a large overdose that presents early. Consider activated charcoal following a recent significant exposure; administer activated charcoal if the patient is awake and cooperative, not vomiting and the airway is protected.
2) CHARCOAL ADMINISTRATION
3) CHARCOAL DOSE

1) MANAGEMENT OF MILD TO MODERATE TOXICITY
2) MANAGEMENT OF SEVERE TOXICITY

1) Monitor vitals signs and mental status.
2) Routine laboratory studies are not needed unless otherwise clinically indicated.
3) Plasma concentrations are not readily available or clinically useful in the management of overdose.
4) Continuously monitor pulse oximetry and obtain blood gases as needed in patients with evidence of CNS and/or respiratory depression. Other causes of CNS depression (eg, benzodiazepines, opioids, tricyclic antidepressants, alcohol) should be ruled out if the diagnosis is not clear or the patient presents with severe intoxication.