Can a patient take naltrexone and Subutex (buprenorphine) together?

Can Naltrexone and Subutex (Buprenorphine) Be Taken Together?

No, naltrexone and Subutex (buprenorphine) are contraindicated for concurrent use and should never be taken together. 1

Absolute Contraindication

The FDA explicitly contraindicates naltrexone in patients currently maintained on partial opioid agonists like buprenorphine (Subutex). 1 This is a black-and-white prohibition, not a relative caution. 1

Why This Combination Is Dangerous

Naltrexone will precipitate severe opioid withdrawal in anyone taking buprenorphine, regardless of whether naloxone is present in the formulation. 1 The presence or absence of naloxone in Suboxone versus Subutex is irrelevant to this interaction—the problem is the naltrexone blocking buprenorphine's partial agonist activity at mu-opioid receptors. 1

Mechanism of Precipitated Withdrawal

• Naltrexone is a pure opioid antagonist that completely blocks all opioid receptors (mu, delta, kappa). 1
• When naltrexone is administered to someone physically dependent on buprenorphine, it displaces buprenorphine from opioid receptors and blocks any remaining agonist activity. 1
• This sudden loss of opioid receptor stimulation triggers acute withdrawal symptoms severe enough to require hospitalization. 1
• Patients transitioning from buprenorphine may remain vulnerable to precipitated withdrawal for up to two weeks after their last buprenorphine dose. 1

The Naloxone Misconception

The naloxone in Suboxone does NOT cause precipitated withdrawal under normal circumstances—it is included only to deter intravenous abuse. 2 When taken sublingually as prescribed, naloxone has poor bioavailability and minimal clinical effect. 2 The critical issue with naltrexone is that it is designed to be systemically active and will precipitate withdrawal whether the patient takes Subutex or Suboxone. 1

Safe Transition Protocol: Buprenorphine to Naltrexone

If transitioning a patient from buprenorphine to naltrexone is clinically indicated (such as moving from maintenance therapy to abstinence-based treatment):

Minimum Opioid-Free Period

• Wait at least 7-14 days after the last buprenorphine dose before initiating naltrexone. 1
• Buprenorphine has a long half-life (24-42 hours) and high receptor affinity, requiring extended clearance time. 1

Pre-Naltrexone Verification

• Confirm the patient has no symptoms of opioid withdrawal before starting naltrexone. 1
• Perform a naloxone challenge test or verify negative urine opioid screen. 1
• Any individual who fails the naloxone challenge test or has a positive urine screen for opioids should not receive naltrexone. 1

Gradual Naltrexone Induction (Research-Supported Approach)

• Research protocols have successfully used very low-dose naltrexone (starting at 0.25 mg) with tapering buprenorphine over 7 days to facilitate outpatient transition. 3
• This approach involves upward titration of naltrexone combined with downward titration of buprenorphine, allowing 70% of patients to successfully receive extended-release naltrexone injection. 3
• One study demonstrated that starting naltrexone on day 2 of a 4-day buprenorphine taper (with escalating naltrexone doses) resulted in moderate withdrawal that resolved by day 5. 4

Critical Monitoring

• Withdrawal symptoms precipitated by naltrexone can be severe and qualitatively different from spontaneous opioid withdrawal. 1
• Monitor for agitation, anxiety, muscle aches, increased pain, sweating, and tachycardia. 5
• Have adjunct medications available (clonidine 0.6-0.7 mg average dose, benzodiazepines up to 20 mg diazepam if needed). 4

Special Consideration: Combined Therapy in Research Settings

One observational study combined naltrexone 50 mg with buprenorphine 4 mg sublingually for 12 weeks, theoretically leaving kappa antagonism as the major effect while mu receptors experienced competitive antagonism/partial agonism. 6 This resulted in 73% retention versus 40% with naltrexone alone, with significantly fewer positive urine screens and reduced dysphoria. 6 However, this remains an experimental approach not endorsed by FDA labeling and should only be attempted in specialized research or treatment settings with intensive monitoring. 1, 6

Clinical Bottom Line

Never prescribe naltrexone to a patient currently taking Subutex or any buprenorphine product. 1 The absence of naloxone in Subutex does not make this combination safer—naltrexone will precipitate severe withdrawal regardless. 1 If transitioning from buprenorphine to naltrexone is necessary, ensure a minimum 7-14 day opioid-free period with documented negative screening before naltrexone initiation. 1