What is the recommended starting dose of suvorexant for insomnia in adults, and how should it be adjusted for patients ≥65 years, moderate hepatic impairment, or when co‑administered with strong CYP3A inhibitors?

Starting Dose of Suvorexant

The recommended starting dose of suvorexant is 10 mg taken once nightly within 30 minutes of bedtime, with a maximum dose of 20 mg for adults under 65 years; for elderly patients (≥65 years), the starting dose is 5 mg with a maximum of 15 mg. 1

Standard Dosing for Adults

• Start with 10 mg nightly for non-elderly adults (18-64 years), taken within 30 minutes of going to bed with at least 7 hours remaining before planned awakening 1
• The dose may be increased to the maximum of 20 mg if the 10 mg dose is well-tolerated but insufficiently effective 1
• At the 20 mg dose, suvorexant demonstrates clinically significant improvements in both sleep onset (reducing latency by 22.3 minutes) and sleep maintenance (reducing wake after sleep onset by 28 minutes, increasing total sleep time by approximately 50 minutes) 2, 3

Elderly Patients (≥65 Years)

• Start with 5 mg nightly in elderly patients 1
• May increase to a maximum of 15 mg if needed and tolerated 1, 4
• The FDA specifically advises lower maximum dosing in elderly patients due to increased risk of next-day sedation and driving impairment at higher doses 4
• Elderly patients showed efficacy at the 15 mg dose across sleep maintenance and onset measures over 3 months of treatment 5

Moderate Hepatic Impairment

• Use 5 mg as the starting dose in patients with moderate hepatic impairment (Child-Pugh category 7-9) 1
• The dose generally should not exceed 10 mg in these patients 1
• Although total drug exposure is similar to healthy subjects, the elimination half-life is prolonged (approximately 19 hours versus 15 hours), increasing the risk of next-day effects 1

Co-Administration with CYP3A Inhibitors

• Strong CYP3A inhibitors (ketoconazole, itraconazole, clarithromycin, ritonavir, nefazodone): Concomitant use is not recommended due to marked increases in suvorexant exposure 1, 6
• Moderate CYP3A inhibitors (diltiazem, erythromycin, fluconazole, verapamil, grapefruit juice): Use a starting dose of 5 mg, with a maximum dose that generally should not exceed 10 mg 1
• Co-administration with diltiazem increases suvorexant exposure approximately 2-fold, while ketoconazole increases it nearly 3-fold 6

Critical Administration Instructions

• Take on an empty stomach – a high-fat meal delays absorption by approximately 1.5 hours without improving efficacy 4, 1
• Avoid alcohol and other CNS depressants due to additive psychomotor impairment and increased risk of next-day sedation 1, 4
• Ensure at least 7 hours available for sleep before planned awakening to minimize next-day impairment 1

Special Considerations for Obese Females

• Obese females have 46% higher drug exposure compared to non-obese females 1
• Consider this higher exposure before increasing the dose in obese female patients 1
• The starting dose remains 10 mg, but dose escalation should be approached more cautiously 1

Contraindications

• Absolutely contraindicated in narcolepsy 4, 7
• Not recommended during pregnancy or lactation 4
• Use with caution in patients with depressive symptoms, compromised respiratory function (asthma, COPD, sleep-disordered breathing), or hepatic/heart failure 4

No Dose Adjustment Required

• Renal impairment: No dose adjustment needed, even in severe renal impairment 1, 7
• Mild hepatic impairment: No dose adjustment required 7
• Age alone: While elderly patients receive lower maximum doses due to safety concerns, age as an isolated factor does not require adjustment in non-elderly adults 1

Common Pitfall to Avoid

The most important pitfall is using strong CYP3A inhibitors concurrently – this can increase suvorexant levels nearly 3-fold and substantially increase the risk of next-day somnolence and impairment 6. Always review the patient's medication list for CYP3A inhibitors before prescribing, and if a moderate inhibitor is present, start at 5 mg rather than the standard 10 mg dose 1.