Is it safe for a patient with a history of opioid addiction to take naltrexone (opioid antagonist) and suboxone (buprenorphine, partial opioid agonist) together?

Do Not Take Naltrexone and Suboxone Together

Naltrexone and Suboxone (buprenorphine/naloxone) are absolutely contraindicated for concurrent use. The FDA explicitly states that naltrexone is contraindicated in patients currently maintained on partial opioid agonists like buprenorphine 1. Taking these medications together will precipitate severe opioid withdrawal that may require hospitalization 1.

Why This Combination Is Dangerous

Naltrexone is an opioid antagonist that will immediately displace buprenorphine from opioid receptors, triggering acute withdrawal. This occurs because:

• Naltrexone competitively blocks mu, kappa, and sigma opioid receptors with high affinity 2
• Buprenorphine is a partial mu-opioid agonist that patients with opioid use disorder depend on for maintenance therapy 3, 4
• When naltrexone displaces buprenorphine, precipitated withdrawal occurs—this is fundamentally different and more severe than spontaneous withdrawal 1

Critical Timing Requirements

If transitioning from Suboxone to naltrexone, patients must be completely off buprenorphine for a minimum of 7-10 days, though up to 2 weeks may be necessary. 1 This extended waiting period is required because:

• Buprenorphine has a long half-life and high receptor binding affinity 2
• Patients transitioning from buprenorphine are particularly vulnerable to precipitated withdrawal for up to two weeks 1
• Any residual buprenorphine in the system will be antagonized by naltrexone, causing severe withdrawal 1

Clinical Presentation of Precipitated Withdrawal

Precipitated withdrawal from naltrexone administration in buprenorphine-maintained patients presents with:

• Severe withdrawal symptoms requiring hospitalization in many cases 1
• Peak withdrawal intensity occurring within hours of naltrexone administration 5
• Symptoms more intense than spontaneous opioid withdrawal 1
• Recent case reports document this occurring even with long-acting formulations 6

If Naltrexone Was Inadvertently Given

If a patient on Suboxone accidentally receives naltrexone, treat with high-dose buprenorphine plus adjunctive medications including benzodiazepines. 6 The management approach includes:

• Immediate administration of high-dose buprenorphine to compete with naltrexone at opioid receptors 6
• Benzodiazepines for symptomatic relief of withdrawal 6
• Clonidine for autonomic symptoms (average 0.64-0.73 mg over treatment course) 5
• Consider sedatives such as diazepam up to 20 mg as needed 5
• Hospital admission may be required for severe cases 1

The Correct Medication for Opioid Use Disorder

For patients with opioid use disorder, continue Suboxone as prescribed—it is FDA-approved first-line medication-assisted treatment. 4 Key points about Suboxone therapy:

• Therapeutic dosing is 8-16 mg daily, with target dose of 16 mg for most patients 4
• Must be combined with behavioral therapies, not used as monotherapy 4
• Demonstrates clinical equivalence to methadone for treatment retention and reducing illicit opioid use 4
• Discontinuing buprenorphine maintenance substantially increases overdose risk if patients return to illicit opioids 7

When Naltrexone Might Be Appropriate

Naltrexone is only appropriate for opioid use disorder AFTER complete detoxification and extended opioid-free period. 1 The patient must:

• Be completely off all opioids for minimum 7-10 days (up to 14 days for buprenorphine) 1
• Have no symptoms of opioid withdrawal 1
• Pass a naloxone challenge test 1
• Have negative urine screen for opioids 1
• Understand they cannot use opioid-containing medications while on naltrexone 1

Common Pitfall to Avoid

Never assume that because naltrexone is combined with bupropion for weight loss (Contrave), it can be safely combined with buprenorphine. The naltrexone/bupropion combination for obesity is explicitly contraindicated for use with chronic opioid therapy, including buprenorphine maintenance 3. This weight loss medication contains 32 mg naltrexone daily 3, which would precipitate severe withdrawal in anyone on Suboxone.