Belsomra
(suvorexant)Dosage & Administration
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Belsomra Prescribing Information
BELSOMRA® (suvorexant) is indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance.
Dosing Information
Use the lowest dose effective for the patient. For all BELSOMRA doses, take no more than once per night within 30 minutes of going to bed (with at least 7 hours remaining prior to planned awakening). Time to effect of BELSOMRA may be delayed if taken with or soon after a meal [see Clinical Pharmacology (12.3)].
The recommended dose for BELSOMRA is 10 mg, taken no more than once per night. If the 10 mg dose is well-tolerated but not effective, the dose can be increased. The maximum recommended dose of BELSOMRA is 20 mg taken no more than once per night.
Special Populations
Exposure to BELSOMRA is increased in obese compared to non-obese patients, and in women compared to men. Particularly in obese women, the increased risk of exposure-related adverse effects should be considered before increasing the dose [see Clinical Pharmacology (12.3)].
Use with CNS Depressants
When BELSOMRA is combined with other CNS depressant drugs, dosage reduction of BELSOMRA and/or the other drug(s) may be necessary because of potentially additive effects [see Warnings and Precautions (5.1)].
Dosage Adjustments with CYP3A Inhibitors
When used with moderate CYP3A inhibitors, the recommended dosage of BELSOMRA is 5 mg taken no more than once per night (the dose generally should not exceed 10 mg). BELSOMRA is not recommended for use with strong CYP3A inhibitors [see Drug Interactions (7.2)].
- 5 mg tablets are yellow, round, film-coated tablets with "5" on one side and plain on the other side.
- 10 mg tablets are green, round, film-coated tablets with "33" on one side and plain on the other side.
- 15 mg tablets are white, oval, film-coated tablets with the corporate logo on one side and "325" on the other side.
- 20 mg tablets are white, round, film-coated tablets with the corporate logo and "335" on one side and plain on the other side.
Pregnancy
Risk Summary
Available data from postmarketing reports with BELSOMRA use in pregnant women are insufficient to establish a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes.
In animal reproduction studies, oral administration of suvorexant to pregnant rats and rabbits during the period of organogenesis decreased maternal body weight and/or weight gain at doses ≥ 30 and 28 times the maximum recommended human dose (MRHD) of 20 mg based on AUC in the rat and rabbit, respectively. Suvorexant caused decreased fetal weight at doses ≥ 86 times the MRHD based on AUC in the rat and did not cause significant fetal toxicity at doses up to 28 times the MRHD based on AUC in the rabbit. The no observed adverse effect levels (NOAELs) for fetal toxicity are 25 and 28 times the MRHD based on AUC in the rat and rabbit, respectively. Oral administration of suvorexant 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 the rat is 25 times the MRHD based on AUC (see Data).
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data
Animal Data
Suvorexant was administered orally to pregnant rats during the period of organogenesis in two separate studies at doses of 30, 150, and 1000 mg/kg/day or 30, 80, and 325 mg/kg/day, which are approximately 3 to 93 times the MRHD based on AUC. Suvorexant decreased maternal weights at doses ≥ 150 mg/kg/day and fetal weights at doses ≥ 325 mg/kg/day. The NOAEL for both maternal and fetal toxicity is 80 mg/kg/day, which is approximately 25 times the MRHD based on AUC.
Suvorexant was administered orally to pregnant rabbits during the period of organogenesis in two separate studies at doses of 40, 100, and 300 mg/kg/day or 50, 150, and 325 mg/kg/day, which are approximately 3 to 70 times the MRHD based on AUC. Suvorexant decreased maternal body weight or weight gain at doses ≥ 150 mg/kg/day. Suvorexant caused excessive maternal toxicity that led to premature deaths at 325 mg/kg/day, which precluded fetal evaluation. Suvorexant did not cause significant fetal toxicity at doses up to 300 mg/kg/day. The NOAELs for maternal and fetal toxicities are 100 mg/kg/day and 300 mg/kg/day, respectively, which are approximately 10 and 28 times the MRHD based on AUC, respectively.
Suvorexant was administered orally to pregnant rats during pregnancy and lactation at doses of 30, 80, and 200 mg/kg/day, which are approximately 8 to 48 times the MRHD based on AUC. Suvorexant caused maternal toxicity of decreased body weight and weight gain and food consumption at 200 mg/kg/day. At this maternally toxic dose, suvorexant caused decreased weight gain in offspring pups. The NOAEL for maternal and developmental toxicity is 80 mg/kg/day, which is approximately 25 times the MRHD based on AUC.
Lactation
Risk Summary
Suvorexant and its metabolite, hydroxy suvorexant, are present in low concentrations in breast milk with a relative infant dose of less than 1% following maternal oral administration (see Data). There are no data on the effects of suvorexant on the breastfed infant, or the effects on milk production.
The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for BELSOMRA and any potential adverse effects on the breastfed infant from BELSOMRA or from the underlying maternal condition.
Data
A single dose (20 mg) milk and plasma lactation study was conducted in 12 healthy lactating women. The mean amount of suvorexant recovered in breast milk was 0.011 mg following a 20 mg maternal dose. The calculated mean daily infant dose was 0.002 mg/kg/day based on the actual infant body weight (i.e., 6.2 kg). The relative infant dose is less than 1% of the maternal dose. Approximately 82% of the amount of suvorexant excreted in breast milk was excreted by 24 hours after a single maternal dose administration.
Suvorexant and its metabolite, hydroxy suvorexant, are present in breast milk and the transfer of hydroxy suvorexant into breast milk is lower than suvorexant (metabolite/parent: 0.13).
Pediatric Use
Safety and effectiveness in pediatric patients have not been established.
Geriatric Use
Of the total number of patients treated with BELSOMRA (n=1784) in controlled clinical safety and efficacy studies, 829 patients were 65 years and over, and 159 patients were 75 years and over. No clinically meaningful differences in safety or effectiveness were observed between these patients and younger patients at the recommended doses [see Clinical Pharmacology (12.3) and Clinical Studies (14)].
Because BELSOMRA can increase drowsiness, patients, particularly the elderly, are at a higher risk of falls [see Warnings and Precautions (5.1)].
Patients with Compromised Respiratory Function
Effects of BELSOMRA on respiratory function should be considered if prescribed to patients with compromised respiratory function.
Obstructive Sleep Apnea
The respiratory depressant effect of BELSOMRA was evaluated after one night and after four consecutive nights of treatment in a randomized, placebo-controlled, 2-period crossover study in patients (n=26) with mild to moderate obstructive sleep apnea. Following once-daily doses of 40 mg, the mean Apnea/Hypopnea Index treatment difference (suvorexant – placebo) on Day 4 was 2.7 (90% CI: 0.22 to 5.09), but there was wide inter- and intra-individual variability such that clinically meaningful respiratory effects of BELSOMRA in obstructive sleep apnea cannot be excluded. BELSOMRA has not been studied in patients with severe obstructive sleep apnea [see Warnings and Precautions (5.5)].
Chronic Obstructive Pulmonary Disease
The respiratory depressant effect of BELSOMRA was evaluated after one night and after four consecutive nights of treatment in a randomized, placebo-controlled, 2-period crossover study in patients (n=25) with mild to moderate chronic obstructive pulmonary disease (COPD). BELSOMRA (40 mg in non-elderly, 30 mg in elderly) had no respiratory depressant effects in patients with mild to moderate COPD, as measured by oxygen saturation. There was wide inter- and intra-individual variability such that clinically meaningful respiratory effects of BELSOMRA in COPD cannot be excluded. BELSOMRA has not been studied in patients with severe COPD [see Warnings and Precautions (5.5)].
Patients with Hepatic Impairment
No dose adjustment is required in patients with mild and moderate hepatic impairment. BELSOMRA has not been studied in patients with severe hepatic impairment and is not recommended for these patients [see Clinical Pharmacology (12.3)].
Patients with Renal Impairment
No dose adjustment is required in patients with renal impairment [see Clinical Pharmacology (12.3)].
BELSOMRA is contraindicated in patients with narcolepsy.
CNS Depressant Effects and Daytime Impairment
BELSOMRA is a central nervous system (CNS) depressant that can impair daytime wakefulness even when used as prescribed. Prescribers should monitor for somnolence and CNS depressant effects, but impairment can occur in the absence of symptoms, and may not be reliably detected by ordinary clinical exam (i.e., less than formal testing of daytime wakefulness and/or psychomotor performance). CNS depressant effects may persist in some patients for up to several days after discontinuing BELSOMRA.
BELSOMRA can impair driving skills and may increase the risk of falling asleep while driving. Discontinue or decrease the dose in patients who drive if daytime somnolence develops. In a study of healthy adults, driving ability was impaired in some individuals taking 20 mg BELSOMRA [see Clinical Studies (14.2)]. Although pharmacodynamic tolerance or adaptation to some adverse depressant effects of BELSOMRA may develop with daily use, patients using the 20 mg dose of BELSOMRA should be cautioned against next-day driving and other activities requiring full mental alertness. Patients taking lower doses of BELSOMRA should also be cautioned about the potential for driving impairment because there is individual variation in sensitivity to BELSOMRA.
Co-administration with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants, alcohol) increases the risk of CNS depression. Patients should be advised not to consume alcohol in combination with BELSOMRA because of additive effects [see Drug Interactions (7.1)]. Dosage adjustments of BELSOMRA and of concomitant CNS depressants may be necessary when administered together because of potentially additive effects. The use of BELSOMRA with other drugs to treat insomnia is not recommended [see Dosage and Administration (2.3)].
The risk of next-day impairment, including impaired driving, is increased if BELSOMRA is taken with less than a full night of sleep remaining, if a higher than the recommended dose is taken, if co-administered with other CNS depressants, or if co-administered with other drugs that increase blood levels of BELSOMRA. Patients should be cautioned against driving and other activities requiring complete mental alertness if BELSOMRA is taken in these circumstances.
Because BELSOMRA can cause drowsiness, patients, particularly the elderly, are at higher risk of falls.
Worsening of Depression/Suicidal Ideation
In clinical studies, a dose-dependent increase in suicidal ideation was observed in patients taking BELSOMRA as assessed by questionnaire. Immediately evaluate patients with suicidal ideation or any new behavioral sign or symptom.
In primarily depressed patients treated with sedative-hypnotics, worsening of depression, and suicidal thoughts and actions (including completed suicides) have been reported. Suicidal tendencies may be present in such patients and protective measures may be required. Intentional overdose is more common in this group of patients; therefore, the lowest number of tablets that is feasible should be prescribed for the patient at any one time.
The emergence of any new behavioral sign or symptom of concern requires careful and immediate evaluation.
Complex Sleep Behaviors
Complex sleep behaviors, including sleep-walking, sleep-driving, and engaging in other activities while not fully awake (e.g., preparing and eating food, making phone calls, having sex), have been reported to occur with the use of hypnotics such as BELSOMRA. These events can occur in hypnotic-naïve as well as in hypnotic-experienced persons. Patients usually do not remember these events. Complex sleep behaviors may occur following the first or any subsequent use of BELSOMRA, with or without the concomitant use of alcohol and other CNS depressants [see Drug Interactions (7.1)]. Discontinue BELSOMRA immediately if a patient experiences a complex sleep behavior.
Sleep Paralysis, Hypnagogic/Hypnopompic Hallucinations, Cataplexy-Like Symptoms
Sleep paralysis, an inability to move or speak for up to several minutes during sleep-wake transitions, and hypnagogic/hypnopompic hallucinations, including vivid and disturbing perceptions by the patient, can occur with the use of BELSOMRA. Prescribers should explain the nature of these events to patients when prescribing BELSOMRA.
Symptoms similar to mild cataplexy can occur, with risk increasing with the dose of BELSOMRA. Such symptoms can include periods of leg weakness lasting from seconds to a few minutes, can occur both at night and during the day, and may not be associated with an identified triggering event (e.g., laughter or surprise).
Patients with Compromised Respiratory Function
Effect of BELSOMRA on respiratory function should be considered if prescribed to patients with compromised respiratory function. BELSOMRA has not been studied in patients with severe obstructive sleep apnea (OSA) or severe chronic obstructive pulmonary disease (COPD) [see Use in Specific Populations (8.6)].
Need to Evaluate for Co-morbid Diagnoses
Because sleep disturbances may be the presenting manifestation of a physical and/or psychiatric disorder, treatment of insomnia should be initiated only after careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated. Worsening of insomnia or the emergence of new cognitive or behavioral abnormalities may be the result of an unrecognized underlying psychiatric or physical disorder and can emerge during the course of treatment with hypnotic drugs such as BELSOMRA.