Can Lunesta (eszopiclone) and alprazolam be prescribed together?

Concurrent Use of Lunesta (Eszopiclone) and Alprazolam

Lunesta (eszopiclone) and alprazolam should not be prescribed together due to the significant risk of respiratory depression, central nervous system depression, and increased mortality risk from their combined sedative effects.

Risks of Concurrent Use

Pharmacological Interaction Concerns

• Both medications are central nervous system depressants that can cause additive sedative effects 1
• Concurrent use increases risk of respiratory depression, which can be potentially fatal 1
• The FDA drug label for eszopiclone specifically notes that coadministration with benzodiazepines like alprazolam can result in pharmacodynamic interactions 2
• When eszopiclone was coadministered with lorazepam (another benzodiazepine similar to alprazolam), they decreased each other's maximum concentration (Cmax) by 22%, indicating a pharmacokinetic interaction 2

Safety Concerns

• The combination significantly increases the risk of:
  • Respiratory depression
  • Excessive sedation
  • Cognitive impairment
  • Falls and accidents
  • Potential for overdose

Evidence from Guidelines

The 2016 MMWR Recommendations and Reports explicitly states: "Benzodiazepines and opioids both cause central nervous system depression and can decrease respiratory drive. Concurrent use is likely to put patients at greater risk for potentially fatal overdose" 1. While this specifically mentions opioids, the same principle applies to multiple CNS depressants like eszopiclone and alprazolam.

The British Journal of Pharmacology (2017) notes that while some hypnotics may not significantly worsen obstructive sleep apnea, the combination of multiple sedating medications increases risk 1. This is particularly concerning as both eszopiclone and alprazolam can cause respiratory depression.

Alternative Approaches

For Insomnia Treatment

• First-line treatment: Cognitive Behavioral Therapy for Insomnia (CBT-I) 3
• If pharmacotherapy is needed: Use a single agent rather than combination therapy
  • Eszopiclone alone (2-3mg) for sleep maintenance insomnia 3
  • Low-dose doxepin (3-6mg) for sleep maintenance insomnia with minimal dependency risk 3
  • Trazodone (50-100mg) if a non-benzodiazepine option is needed 3

For Anxiety with Insomnia

• Consider a single medication that addresses both conditions:
  • Mirtazapine (7.5-15mg) for combined insomnia and anxiety 3
  • An SSRI for anxiety with a separate, short-term sleep medication if absolutely necessary 3

Monitoring Requirements if Combination Cannot Be Avoided

In rare clinical situations where alternatives have failed and the combination must be used (which should be extremely uncommon):

1. Use the lowest possible doses of both medications
2. Implement close clinical monitoring for:
   • Respiratory depression
   • Excessive sedation
   • Cognitive impairment
   • Risk of falls
3. Limit the duration of concurrent therapy to the shortest possible time
4. Consider cardiorespiratory monitoring in high-risk patients 1
5. Educate patients about the risks of combining these medications
6. Avoid alcohol and other CNS depressants completely

Conclusion

The concurrent use of Lunesta (eszopiclone) and alprazolam presents significant risks with limited additional benefits. The potential for respiratory depression, excessive sedation, and increased mortality strongly argues against this combination. Clinicians should select a single agent appropriate for the patient's primary condition or choose alternatives that address both insomnia and anxiety without the risks associated with combining these two medications.