| Active Ingredient | SUVOREXANT |
|---|
| Drug Name | FDA Application No. | Company | Dosage Form;Route | Strength | RLD Strength | Original Approval or Tentative Approval Date |
Exclusivity Expiration (NCE) |
Exclusivity Expiration (ODE) |
Chemical Type |
Review Classification |
Marketing Status |
TE Code |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| BELSOMRA | (NDA) 204569 | MERCK SHARP DOHME | TABLET;ORAL | 5MG, 10MG, 15MG, 20MG | 20MG | August 13, 2014 | August 13, 2019 | - | 1 New molecular entity (NME) | S Standard review drug | Prescription | None |
| Parameters | Details |
|---|---|
| Structural Formula |
 |
| Chemical Name | [(7R)-4-(5-chloro-2-benzoxazolyl) hexahydro-7-methyl-1H-1,4-diazepin-1-yl][5-methyl-2-(2H-1,2,3-triazol2-yl)phenyl]methanone |
| CAS No | 1030377-33-3 |
| Molecular Formula | C23H23ClN6O2 |
| Molecular Weight | 450.92 |
| Appearance | a white to off-white powder |
| Solubility | It is insoluble in water. |
| Water Solubility | 0.117 mg/mL (Predicted) |
| Polymorphism | - |
| pKa (Strongest Acidic) | - |
| pKa (Strongest Basic) | 0.25 (Predicted) |
| Log P | 3.86 (Predicted) |
| Identification | - |
| Degradation | - |
| Hygroscopic | - |
| Photostability study | - |
| Melting Point | - |
| BCS Class | - |
| Manufacture of API | - |
| Parameters | Details |
|---|---|
| Indications and Usage | BELSOMRA (suvorexant) is indicated for the treatment of insomnia characterized by difficulties with sleep onset and/or sleep maintenance. |
| Dosage and Administration |
Use the lowest dose effective for the patient. The recommended dose for BELSOMRA is 10 mg, taken no more than once per night and within 30 minutes of going to bed, with at least 7 hours remaining before the planned time of awakening. 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 once daily. |
| Mechanism of action |
The mechanism by which suvorexant exerts its therapeutic effect in insomnia is presumed to be through antagonism of orexin receptors. The orexin neuropeptide signaling system is a central promoter of wakefulness. Blocking the binding of wake-promoting neuropeptides orexin A and orexin B to receptors OX1R and OX2R is thought to suppress wake drive. Antagonism of orexin receptors may also underlie potential adverse effects such as signs of narcolepsy/cataplexy. Genetic mutations in the orexin system in animals result in hereditary narcolepsy; loss of orexin neurons has been reported in humans with narcolepsy. |
| Absorption |
Suvorexant exposure increases in a less than strictly dose-proportional manner over the range of 10-80 mg because of decreased absorption at higher doses. Suvorexant pharmacokinetics are similar in healthy subjects and patients with insomnia. Suvorexant peak concentrations occur at a median Tmax of 2 hours (range 30 minutes to 6 hours) under fasted conditions. The mean absolute bioavailability of 10 mg is 82%. |
| Food Effect | Ingestion of suvorexant with a high-fat meal resulted in no meaningful change in AUC or Cmax but a delay in Tmax of approximately 1.5 hours. Suvorexant may be taken with or without food; however for faster sleep onset, suvorexant should not be administered with or soon after a meal. |
| Distribution | The mean volume of distribution of suvorexant is approximately 49 liters. Suvorexant is extensively bound (>99%) to human plasma proteins and does not preferentially distribute into red blood cells. Suvorexant binds to both human serum albumin and 1-acid glycoprotein. |
| Metabolism | Suvorexant is mainly eliminated by metabolism, primarily by CYP3A with a minor contribution from CYP2C19. The major circulating entities are suvorexant and a hydroxy-suvorexant metabolite. This metabolite is not expected to be pharmacologically active. |
| Elimination | The primary route of elimination is through the feces, with approximately 66% of radiolabeled dose recovered in the feces compared to 23% in the urine. The systemic pharmacokinetics of suvorexant are linear with an accumulation of approximately 1- to 2-fold with once-daily dosing. Steady-state is achieved by 3 days. The mean t1/2 is approximately 12 hours (95% CI: 12 to 13). |
| Peak plasma time (Tmax) | 2 hours (range 30 minutes to 6 hours) (Fasted) |
| Half life | 12 hours |
| Bioavailability | - |
| Age, gender | Gender, age, body mass index (BMI), and race were included as factors assessed in the population pharmacokinetic model to evaluate suvorexant pharmacokinetics in healthy subjects and to predict exposures in the patient population. Age and race are not predicted to have any clinically meaningful changes on suvorexant pharmacokinetics; therefore, no dose adjustment is warranted based upon these factors. |
| DMF | Status | Type | Submit Date | Holder |
|---|---|---|---|---|
| Not Available | ||||
| Parameters | Details | ||||
|---|---|---|---|---|---|
| Strength | 5MG | 10MG | 15MG | 20MG | |
| Excipients used | polyvinylpyrrolidone/vinyl acetate copolymer (copovidone), microcrystalline cellulose, lactose monohydrate, croscarmellose sodium, and magnesium stearate | ||||
| Composition of coating material | lactose monohydrate, hypromellose, titanium dioxide, triacetin, iron oxide yellow and iron oxide black | lactose monohydrate, hypromellose, titanium dioxide, triacetin, iron oxide yellow and FD&C Blue #1/Brilliant Blue FCF Aluminum Lake | lactose monohydrate, hypromellose, titanium dioxide, triacetin | ||
| Composition of caspule shell | - | ||||
| Pharmaceutical Development | - | ||||
| Manufacture of the product | - | ||||
| Tablet / Capsule Image |
|
||||
| Appearance | yellow, round, film-coated tablets with “5” on one side and plain on the other side | green, round, film-coated tablets with “33” on one side and plain on the other side | white, oval, film-coated tablets with the Merck logo on one side and “325” on the other side | white, round, film-coated tablets with the Merck logo and “335” on one side and plain on the other side. | |
| Imprint code / Engraving / Debossment | Debossed with “5” on one side and plain on the other side | Debossed with “33” on one side and plain on the other side | Debossed with the Merck logo on one side and “325” on the other side | Debossed with the Merck logo and “335” on one side and plain on the other side | |
| Score | no score | no score | no score | no score | |
| Color | Yellow | Green | White | White | |
| Shape | Round | Round | Oval | Round | |
| Dimension | 5mm | 6mm | 10mm | 8mm | |
| Mfg by | - | ||||
| Mfg for | - | ||||
| Marketed by | Merck Sharp & Dohme Corp. (US) | ||||
| Distributed by | - | ||||
| Application No. | Prod No | Patent No | Patent Expiration | Drug Substance Claim | Drug Product Claim | Patent Use Code | Delist Requested | Link |
|---|---|---|---|---|---|---|---|---|
| N204569 | 1 | 7951797 | November 20, 2029 | Y | Y | U - 620 | - | Download |
| USP Apparatus | Speed (RPMs) | Medium | Volume (mL) | Recommended Sampling Times (minutes) | Date Updated |
|---|---|---|---|---|---|
| II (Paddle) with sinker | 75 | 0.4% Sodium Lauryl Sulfate in Water | 900 | 5, 10, 15, 20, 30 and 45 | September 3, 2015 |
| Label | Link |
|---|---|
| FDA label | Download |
| FDA chemistry review | Download |
| FDA Pharmacology Review(s) | Download |
| FDA Clinical Pharmacology Biopharmaceutics Review(s) | Download |
| FDA BE Recommendation | Download |
| European Public Assessment Report |
| - |
| www.accessdata.fda.gov, www.drugbank.ca, www.ema.europa.eu, www.medicines.org.uk, dailymed.nlm.nih.gov, www.drug.com |
