Suvorexant: pharmacokinetics, clinical applications and side effects

General Description

Suvorexant is a medication used for treating insomnia in adults and pediatric patients. It acts by blocking signals that promote wakefulness, helping patients fall asleep faster and maintain sleep. Clinical trials have shown its effectiveness in improving sleep and daytime functioning. When taken on an empty stomach, it reaches maximum concentration in about 2 hours. It has a high bioavailability of approximately 82% and steady state is achieved within 3 days of regular dosing. Suvorexant is extensively bound to plasma proteins and has a large volume of distribution. It is primarily metabolized by CYP3A enzymes and eliminated mainly through feces and urine. Common side effects include somnolence, fatigue, and dose-dependent increases in cholesterol levels. Suicidal ideation, sleep paralysis, and hallucinations are potential side effects that should be monitored. Suvorexant is generally well tolerated, with no withdrawal symptoms or physical dependence observed. Discontinuing the medication does not result in rebound insomnia.

Figure 1. Tablets of suvorexant

Pharmacokinetics

Suvorexant is a medication with specific pharmacokinetic characteristics. When taken on an empty stomach, it reaches maximum plasma concentration in about 2 hours. The mean bioavailability of a 10 mg dose is approximately 82%. Administering suvorexant with a high-fat meal does not significantly affect its systemic exposure but may delay the time to maximum concentration by around 1.5 hours. Steady state is achieved within 3 days of regular dosing. The drug has a large volume of distribution, around 49 L, and binds extensively to plasma proteins, including albumin and a1-acid glycoprotein. It does not accumulate preferentially in red blood cells. Suvorexant is primarily metabolized by CYP3A enzymes, with a minor contribution from CYP2C19. The main circulating compounds are the unchanged drug and a non-pharmacologically active hydroxyl metabolite. Elimination occurs mainly through feces (66%) and urine (23%). The average elimination half-life of suvorexant is approximately 12 hours. Studies have been conducted on individuals with impaired renal function and hepatic insufficiency. ¹

Clinical applications

Suvorexant is a prescription medication used for the treatment of insomnia in adults and pediatric patients. It is an orexin receptor antagonist that works by binding to orexin receptors in the brain, promoting sleep by blocking signals that promote wakefulness. Clinical trials have shown that suvorexant effectively helps patients with insomnia to fall asleep faster and maintain sleep. It has also been associated with improvements in daytime functioning, such as reduced fatigue and increased alertness. When prescribing suvorexant, healthcare professionals need to consider factors like the patient's medical history, allergies, other medications they are taking, and potential side effects. Individual evaluation is important to determine if suvorexant is the appropriate treatment option for each patient. In conclusion, suvorexant has been clinically proven as a beneficial treatment for insomnia, assisting patients in falling asleep and staying asleep. Collaboration with a healthcare professional is essential to determine its suitability for individual patients. ²

Side effect

Suvorexant, administered at doses of 15-40 mg once daily, has been generally well tolerated in clinical trials over a one-year period. The most common side effects reported were somnolence and fatigue, which were usually mild to moderate in severity and temporary. Other potential side effects include suicidal ideation, sleep paralysis, and hypnagogic / hypnopompic hallucinations. It is recommended to monitor for these symptoms. Somnolence and increased serum cholesterol levels were observed to be dose-dependent. Tolerability profiles were similar across different patient populations, with certain side effects occurring more frequently in female patients. Discontinuing suvorexant did not result in withdrawal symptoms or rebound insomnia, and no signs of physical dependence were observed during prolonged use. Behavioral changes were observed in canines but not in non-human primates or in human trials. Falls reported during the trials were not linked to somnolence or impaired coordination, although mild cataplexy-like symptoms were noted. ³

Reference

1. Merck Co. BELSOMRA. (suvorexant) US prescribing information. 2014. https://www.merck.com/product/usa/pi_circulars/b/belsomra/belsomra_pi.pdf.

2. Suvorexant. In: LiverTox: Clinical and Research Information on Drug-Induced Liver Injury. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; September 25, 2021.

3. Yang LP. Suvorexant: first global approval. Drugs, 2014, 74(15):1817-1822.