Can Valium (diazepam) and Rozerem (ramelteon) be taken together at bedtime?

Can Valium and Rozerem Be Taken Together at Bedtime?

Yes, Valium (diazepam) and Rozerem (ramelteon) can be taken together at bedtime, but this combination requires caution due to the FDA black box warning about combining benzodiazepines with other sedating medications, which carries risks of respiratory depression and death. 1

Key Safety Considerations

FDA Black Box Warning

• The FDA has issued a black box warning specifically about combining opioid medications with benzodiazepines and other sedating medications, noting possible serious effects including slowed or difficult breathing and death. 1
• While this warning primarily targets opioid-benzodiazepine combinations, the principle of caution applies when combining any CNS depressants, including benzodiazepines with sleep medications 1

Ramelteon's Safety Profile

• Ramelteon is a selective MT1/MT2 melatonin receptor agonist with a fundamentally different mechanism than benzodiazepines—it does not act on GABA receptors 2, 3
• Ramelteon has no depressant effects on the nervous system and is not expected to affect respiratory control 4
• Studies demonstrate ramelteon does not worsen sleep apnea in patients with mild to moderate obstructive sleep apnea, showing no effect on apnea-hypopnea index or oxygen saturation 4
• Ramelteon is not classified as a controlled substance and has no abuse or dependence potential 5, 3

Clinical Decision Algorithm

For patients requiring both medications:

1. Assess respiratory risk factors:

   • History of sleep apnea (ramelteon is safe even in mild-moderate OSA) 4
   • COPD or other pulmonary disease
   • Age >65 (increased risk of confusion, falls, and morning incoordination with benzodiazepines) 1
   • Concurrent use of other CNS depressants

2. If combining is necessary:

   • Use the lowest effective dose of diazepam (benzodiazepines at 0.5-1.0 mg can worsen sleep apnea) 1
   • Monitor for morning sedation, confusion, and motor incoordination—common benzodiazepine side effects 1
   • Consider that 58% of patients on clonazepam (another benzodiazepine) for sleep disorders experienced moderate-to-severe side effects 1

3. Strongly consider alternatives:

   • Ramelteon alone (8 mg) is effective for sleep onset insomnia and is recommended by the American Academy of Sleep Medicine 6
   • For patients with addiction history, ramelteon is preferred over benzodiazepines due to lack of dependence risk 6
   • Low-dose doxepin (3-6 mg) for sleep maintenance insomnia 7

Common Pitfalls to Avoid

• Do not assume ramelteon carries the same respiratory risks as benzodiazepines—it has a completely different mechanism and safety profile 2, 4
• Avoid long-term benzodiazepine use when possible—clonazepam has a 30-40 hour half-life leading to accumulation and increased fall risk 1
• Monitor for next-day cognitive impairment, particularly with diazepam which has a long half-life 1
• Be aware that benzodiazepines should be used with caution in neurodegenerative disorders 1

Bottom Line

While the combination is not absolutely contraindicated, the safer approach is to use ramelteon alone for sleep onset difficulties, reserving benzodiazepines only when ramelteon proves insufficient, and then using the lowest effective dose with close monitoring for respiratory depression and cognitive side effects. 1, 6, 4