Belsomra (Tablets) Instructions for Use

Marketing Authorization Holder

MSD Pharmaceuticals, LLC (Russia)

Manufactured By

MSD International GmbH (Puerto Rico Branch), LLC (Puerto Rico)

Labeled By

ANDERSONBRECON, Inc. (USA)

ATC Code

N05CM19 (Suvorexant)

Active Substance

Suvorexant (Rec.INN registered by WHO)

Dosage Forms

	Belsomra	Film-coated tablets, 10 mg: 10 or 30 pcs.
		Film-coated tablets, 15 mg: 10 or 30 pcs.
		Film-coated tablets, 20 mg: 10 or 30 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets light green in color, round, biconvex, engraved with “33” on one side, smooth on the other side.

Excipients: copovidone – 40 mg, lactose monohydrate – 20.94 mg, microcrystalline cellulose – 41.25 mg, croscarmellose sodium – 12.5 mg, magnesium stearate – 0.313 mg.

Film coating composition: opadry II green 39K110000 – 5.6 mg: lactose monohydrate – 35%, hypromellose-2910 – 33%, titanium dioxide – 23.58%, triacetin – 8%, brilliant blue aluminum lake dye – 0.23%, yellow iron oxide – 0.19%.

10 pcs. – PA/Al/PVC blisters (1) – cardboard packs.
10 pcs. – PA/Al/PVC blisters (3) – cardboard packs.

Film-coated tablets white in color, oval, biconvex, with the company logo on one side and engraved with “325” on the other side.

Excipients: copovidone – 60 mg, lactose monohydrate – 31.41 mg, microcrystalline cellulose – 61.88 mg, croscarmellose sodium – 18.75 mg, magnesium stearate – 0.469 mg.

Film coating composition: opadry II white 39K18561 – 8 mg: lactose monohydrate – 35%, hypromellose-2910 – 33%, titanium dioxide – 24%, triacetin – 8%.

10 pcs. – PA/Al/PVC blisters (1) – cardboard packs.
10 pcs. – PA/Al/PVC blisters (3) – cardboard packs.

Film-coated tablets white in color, round, biconvex, engraved with “335” and the company logo on one side, smooth on the other side.

Excipients: copovidone – 80 mg, lactose monohydrate – 41.88 mg, microcrystalline cellulose – 82.5 mg, croscarmellose sodium – 25 mg, magnesium stearate – 0.625 mg.

Film coating composition: opadry II white 39K18561 – 8.8 mg: lactose monohydrate – 35%, hypromellose-2910 – 33%, titanium dioxide – 24%, triacetin – 8%.

10 pcs. – PA/Al/PVC blisters (1) – cardboard packs.
10 pcs. – PA/Al/PVC blisters (3) – cardboard packs.

Clinical-Pharmacological Group

Hypnotic drug

Pharmacotherapeutic Group

Hypnotic agent

Pharmacological Action

Selective, reversible, high-affinity antagonist of orexin receptors OX1R (Ki 0.55 nmol/L) and OX2R (Ki 0.35 nmol/L).

The orexin neuropeptide signaling system is a key mechanism that promotes wakefulness. Nerve cells that produce orexin are located in the hypothalamus and influence brain neurons responsible for the wakefulness process. Suvorexant initiates the physiological process of the brain transitioning from wakefulness to sleep by reversibly blocking the binding of wakefulness neuropeptides (orexins A and B) to OX1R and OX2R receptors, thereby suppressing the maintenance of wakefulness.

Suvorexant does not possess direct pharmacological activity or binding capacity (Ki>10 µmol/L) for GABA, serotonin, dopamine, norepinephrine, melatonin, histamine, acetylcholine, or opioid receptors.

Pharmacokinetics

In the dose range from 10 mg to 80 mg, suvorexant exposure increases in a less than dose-proportional manner due to decreased absorption. The pharmacokinetic parameters of suvorexant are the same in healthy volunteers and patients with insomnia.

The C_max of suvorexant is achieved on average within 2 hours (range from 30 minutes to 6 hours) when the drug is taken on an empty stomach. The mean absolute bioavailability of suvorexant at a 20 mg dose is 62% (5th-95th percentile: from 55% to 69%).

Taking suvorexant with a high-fat meal resulted in a minor change in AUC or C_max and an increase in T_max by approximately 1.5 hours. Suvorexant can be taken without regard to meals. However, to achieve a faster sleep onset effect, Suvorexant should not be taken during or immediately after a meal.

The mean V_d of suvorexant is approximately 49 L. The binding of suvorexant to human plasma proteins is >99%, and it barely penetrates erythrocytes. Suvorexant binds to human serum albumin and alpha₁-acid glycoprotein.

Suvorexant is eliminated from the body mainly by metabolism, primarily via the CYP3A isoenzyme with a minor contribution from the CYP2C19 isoenzyme. The main circulating substances are Suvorexant and the metabolite hydroxysuvorexant. The metabolite is not expected to be pharmacologically active.

The primary route of elimination for suvorexant is via the intestine: about 66% of the radioactively labeled dose is excreted via the intestine, 23% via the kidneys. Suvorexant is eliminated from the body predominantly as metabolites, with less than 1% of the administered dose found unchanged as suvorexant in feces and urine.

With once-daily dosing, systemic pharmacokinetics are linear with dose accumulation not exceeding two-fold.

Steady state after once-daily administration of suvorexant is reached within 3 days and corresponds to a mean T_1/2 of about 12 hours (95% CI: from 12 to 13).

Suvorexant exposure after a single dose was similar in patients with moderate hepatic impairment (Child-Pugh score 7-9) and in healthy volunteers. However, the apparent terminal T_1/2 of suvorexant increased from approximately 15 hours (range 10-22 hours) in healthy volunteers to 19 hours (range 11-49 hours) in patients with moderate hepatic impairment.

Indications

Treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance.

ICD codes

Dosage Regimen

Take Belsomra orally.

Administer once per night, immediately before bedtime.

Ensure at least 7 hours remain before planned awakening.

Take the tablet within 30 minutes of going to bed.

For faster sleep onset, do not take during or immediately after a meal.

The recommended dose is 10 mg.

The maximum recommended dose is 20 mg.

Use the lowest effective dose for the shortest duration necessary.

For patients taking moderate CYP3A inhibitors, do not exceed a 10 mg dose.

Concomitant use with strong CYP3A inhibitors is contraindicated.

Assess patient response after 7-10 days of treatment.

Discontinue treatment gradually if necessary to reduce potential withdrawal effects.

Monitor for next-day impairment, including drowsiness and reduced psychomotor performance.

Do not operate vehicles or machinery until the drug’s effects are fully known.

Avoid alcohol consumption during treatment.

Adverse Reactions

Digestive system disorders ≥2% – diarrhea, dry mouth.

Nervous system disorders ≥2% – headache, drowsiness, dizziness.

Psychiatric disorders ≥2% – unusual dreams

Respiratory system disorders ≥2% – cough, upper respiratory tract infections.

Psychiatric disorders ≥2% – unusual dreams. In clinical studies, hypnagogic/hypnopompic hallucinations were reported in <1% of cases.

Contraindications

Severe hepatic impairment; narcolepsy and cataplexy; concomitant use with strong CYP3A isoenzyme inhibitors (including ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin, and conivaptan); concomitant use with other drugs used to treat insomnia; pregnancy, lactation (breastfeeding); age under 18 years (efficacy and safety not studied); hypersensitivity to suvorexant.

Use in Pregnancy and Lactation

Contraindicated for use during pregnancy and lactation (breastfeeding).

Use in Renal Impairment

The drug is approved for use in renal impairment

Pediatric Use

The drug is contraindicated for use in children and adolescents under 18 years of age

Special Precautions

With caution: history of tendency or abuse of drugs or alcohol; respiratory disorders, including COPD.

Suvorexant is a CNS depressant and may impair daytime wakefulness, even when used as prescribed. The physician prescribing suvorexant should monitor the patient for the emergence of drowsiness and CNS depression symptoms.

When suvorexant is used concomitantly with other drugs that have a depressant effect on the CNS (e.g., benzodiazepines, opioid analgesics, tricyclic antidepressants).

The risk of next-day impairment, including impaired ability to drive vehicles, increases if the time between taking suvorexant and awakening is insufficient for a full night’s sleep, as well as when taken at a dose exceeding the recommended one, when taken concomitantly with other CNS depressants (e.g., benzodiazepines, opioids, tricyclic antidepressants), or when taken concomitantly with drugs that increase the blood concentration of suvorexant.
Concomitant use of suvorexant with other drugs used to treat insomnia is not recommended.

Since sleep disturbances may be a manifestation of physical and/or mental disorders, treatment of insomnia should only be initiated after a thorough examination of the patient. Failure of therapy within 7-10 days may indicate the presence of a primary psychiatric and/or other condition requiring diagnosis. Worsening of insomnia or the emergence of new cognitive or behavioral abnormalities may be the result of an undiagnosed underlying psychiatric or physical disorder, rather than insomnia itself, and may manifest during the course of treatment with suvorexant.

The occurrence of various cognitive and behavioral disorders (e.g., amnesia, anxiety, hallucinations, and other neuropsychiatric symptoms) associated with the use of hypnotic drugs similar to suvorexant has been reported. Reports have been received of episodes of complex sleep behaviors, such as “sleep-driving” (i.e., driving a vehicle while not fully awake after taking a hypnotic drug) or other episodes of complex sleep behaviors (sleepwalking, preparing and eating food while asleep), accompanied by amnesia for the events and associated with the use of hypnotic drugs. These reactions can occur in both patients who have not previously taken hypnotic drugs and in patients who have taken such drugs before. Consumption of alcohol and other CNS depressants may increase the risk of such behavior. Use of suvorexant should be discontinued in patients who report episodes of complex sleep behaviors.

Worsening of depression, including the development of suicidal thoughts and actions (including completed suicides) has been reported in patients with primary depression who were taking hypnotic drugs. The appearance of any new behavioral signs or symptoms of depression requires a thorough and immediate evaluation of the patient’s condition.

A clinically significant effect of suvorexant on respiratory function in patients with sleep apnea syndrome and in patients with COPD cannot be excluded. A study of suvorexant in patients with severe sleep apnea syndrome and severe COPD has not been conducted.

No clinically significant differences in safety or efficacy were observed in patients over 65 years of age compared to younger patients when using suvorexant. However, increased sensitivity in some elderly patients cannot be ruled out.

Caution is required when using in patients prone to drug abuse.

The patient should be warned to refrain from consuming alcohol concomitantly with suvorexant.

Effect on ability to drive vehicles and operate machinery

Suvorexant may adversely affect the ability to drive vehicles and operate machinery, and may increase the risk of falling asleep while driving. After taking suvorexant, patients should avoid hazardous activities such as driving a car or operating other dangerous machinery. Furthermore, the patient should be warned about possible next-day performance impairment after taking suvorexant.

Drug Interactions

When suvorexant is used concomitantly with ketoconazole (a strong CYP3A isoenzyme inhibitor), suvorexant exposure increases by 2.79 times. Concomitant use with strong CYP3A isoenzyme inhibitors (ketoconazole, itraconazole, posaconazole, clarithromycin, nefazodone, ritonavir, saquinavir, nelfinavir, indinavir, boceprevir, telaprevir, telithromycin, and conivaptan) is not recommended.

When suvorexant is used concomitantly with diltiazem (a moderate CYP3A isoenzyme inhibitor), suvorexant exposure increases by 2.05 times. The dose of suvorexant should not exceed 10 mg when used concomitantly with moderate CYP3A isoenzyme inhibitors (amprenavir, aprepitant, atazanavir, ciprofloxacin, diltiazem, erythromycin, fluconazole, fosamprenavir, crizotinib, imatinib, verapamil, grapefruit juice).

A significant decrease in suvorexant exposure is possible when used concomitantly with strong CYP3A isoenzyme inducers (rifampicin, carbamazepine, and phenytoin), leading to reduced efficacy of suvorexant.

With sequential multiple administration, Suvorexant exhibits weak inhibitory properties towards the CYP3A isoenzyme and intestinal P-glycoprotein.

When suvorexant is used concomitantly with midazolam (a sensitive CYP3A isoenzyme substrate), the exposure of most drugs metabolized by the CYP3A isoenzyme increases slightly. It is not expected that the use of suvorexant will lead to an increase in plasma concentrations to clinically significant levels.

When suvorexant is used concomitantly with digoxin, the concentration of digoxin increases slightly due to inhibition of intestinal P-glycoprotein. In case of concomitant use of suvorexant with digoxin, digoxin concentration should be monitored according to clinical indications.

When used concomitantly with alcohol, an enhancement of psychomotor impairment was observed.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.