Should patients on buprenorphine (Suboxone) be given Klonopin (clonazepam)?

Concomitant Use of Clonazepam (Klonopin) with Buprenorphine (Suboxone) Should Be Avoided

Patients on buprenorphine (Suboxone) should not be given clonazepam (Klonopin) due to the significant risk of respiratory depression, sedation, and potential fatal outcomes from this combination.

Rationale for Avoiding This Combination

Safety Concerns

• The FDA drug label for clonazepam explicitly warns about potentially fatal additive effects when benzodiazepines are used with opioids, including buprenorphine 1
• Benzodiazepines interact at GABA-A sites while opioids interact primarily at mu receptors, creating a dangerous synergistic effect on respiratory depression 1
• Multiple studies have documented fatalities attributed to combinations of buprenorphine with benzodiazepines 2, 3

Pharmacological Interaction

• While buprenorphine alone has a ceiling effect for respiratory depression, this safety advantage is negated when combined with benzodiazepines 2
• The combination produces respiratory depression through a pharmacodynamic interaction affecting multiple ventilatory parameters 4
• Unlike respiratory depression from other opioids, buprenorphine-induced respiratory depression is poorly responsive to naloxone, making overdose management more challenging 2

Clinical Management Algorithm

For Patients Already on Buprenorphine Requiring Anxiolytic Treatment:

1. First-line alternatives to benzodiazepines:

   • Non-benzodiazepine anxiolytics (e.g., buspirone)
   • SSRIs for anxiety disorders
   • Trazodone for insomnia 5
   • Gabapentin for anxiety symptoms 5

2. If anxiety/insomnia persists despite alternatives:

   • Consider mirtazapine or low-dose tricyclic antidepressants 5
   • Behavioral interventions (CBT, relaxation techniques)
   • Consult psychiatry for specialized management

For Patients Already on Both Medications:

1. Do not abruptly discontinue either medication

2. Develop a tapering plan for the benzodiazepine:

   • Gradual dose reduction (typically 10-25% every 1-2 weeks)
   • Monitor for withdrawal symptoms
   • Consider temporary switch to a longer-acting benzodiazepine if using short-acting ones

3. During tapering:

   • Increase monitoring frequency
   • Educate patient and family about overdose risk signs
   • Consider prescribing naloxone kit

Special Considerations

Pain Management in Buprenorphine Patients

• If the patient requires pain management, non-opioid analgesics should be maximized first 6
• For patients on buprenorphine for pain management, consider dividing the daily buprenorphine dose and administering it every 6-8 hours to optimize analgesic effects 5
• Adjunctive non-opioid therapies such as NSAIDs, acetaminophen, or topical agents can enhance pain management 6

Perioperative Management

• For perioperative pain management in patients on buprenorphine, individualize treatment based on the prescribed daily dose, indication for treatment, risk of relapse, and expected level of postsurgical pain 5
• Avoid concomitant use of buprenorphine with QT-prolonging agents 5

Common Pitfalls to Avoid

1. Assuming buprenorphine's ceiling effect on respiratory depression makes benzodiazepine combinations safe - This is false; the combination negates this safety advantage 3

2. Relying on naloxone to reverse overdose - Buprenorphine-induced respiratory depression requires continuous rather than bolus administration of naloxone, and may not be fully reversible in combination overdoses 7

3. Abrupt discontinuation of either medication - This can precipitate withdrawal symptoms that may complicate management 5

4. Underestimating the risk - Even at therapeutic doses, this combination can cause significant respiratory depression, particularly in vulnerable patients 8

The evidence clearly demonstrates that the risks of combining clonazepam with buprenorphine outweigh any potential benefits, and alternative approaches should be pursued for patients requiring treatment for both opioid use disorder and anxiety/seizure disorders.