Concomitant use of a strong CYP enzyme inducer such as rifampin may increase ramelteon metabolism and reduce serum ramelteon, which might decrease its efficacy in some cases. Whether increasing the ramelteon dosage counters this interaction is unknown.
Strong CYP 2C9 inhibitors such as fluconazole or strong CYP 3A4 inhibitors such as ketoconazole can raise serum ramelteon and might increase the risk of adverse events in some persons.
Dosing
Start ramelteon at 8 mg nightly, and tell patients to take it within 30 minutes of going to bed.
Because high-fat food slows its absorption, advise patients not to take ramelteon within 1 hour of eating a high-fat meal.
Ramelteon’s efficacy and side effects do not appear to be dose-dependent when given at 8 to 64 mg/d. Whether dosages >64 mg/d increase side-effect risk or therapeutic effect is unknown.
As with other hypnotics, supplement ramelteon therapy with sleep hygiene education and relaxation techniques.
Clinical implications
Ramelteon appears to help patients who have trouble falling asleep.
Because no other prescription medication targets melatonin neurotransmitters, no precedent and little data exist to guide patient choice, dosing, and treatment duration. Effects of ramelteon use >5 weeks are unknown. Clinical use and future research should uncover more information about ramelteon’s properties.
Related resources
- Ramelteon Web site. www.rozerem.com.
- Arendt J, Skene DJ. Melatonin as a chronobiotic. Sleep Med Rev 2005;9:25-39.
- Scheer FA, Czeisler CA. Melatonin, sleep, and circadian rhythms. Sleep Med Rev 2005;9:5-9.
Drug brand names
- Fluconazole • Diflucan
- Fluvoxamine • Luvox
- Ketoconazole • Nizoral
- Ramelteon • Rozerem
- Rifampin • Rifadin
- Triazolam • Halcion
Disclosures
Dr. Krystal receives research/grant support, is a consultant to, or is a speaker for Cephalon, Cyberonics, GlaxoSmithKline, Johnson & Johnson, King Pharmaceuticals, Mecta Corp., Merck and Co., Neurocrine Biosciences, Neurogen Corp., Neuronetics, Organon, Pfizer, Respironics, Sanofi-Aventis, Sepracor, Somaxon Pharmaceuticals, Takeda Pharmaceuticals North America, and TransOral Pharmaceuticals.