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

Can a Patient Take Subutex and Naltrexone Together?

Direct Answer

No, a patient cannot take Subutex (buprenorphine) and naltrexone together—this combination is absolutely contraindicated and potentially dangerous. 1

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FDA Contraindication

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

• Naltrexone is contraindicated in patients receiving any opioid agonists or partial agonists, including buprenorphine 1
• Administering naltrexone to someone on buprenorphine will precipitate acute opioid withdrawal 1
• Any individual with a positive urine screen for opioids should not receive naltrexone 1

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Pharmacologic Mechanism of Harm

Naltrexone is a competitive opioid antagonist with higher affinity for mu-opioid receptors than buprenorphine, meaning it will displace buprenorphine from these receptors and trigger severe withdrawal. 2

• Naltrexone has high affinity but zero efficacy at mu, kappa, and sigma opioid receptors 2
• When naltrexone displaces buprenorphine from receptors, the patient experiences precipitated withdrawal—a medical emergency characterized by severe agitation, anxiety, muscle aches, sweating, tachycardia, and intense suffering 3
• This precipitated withdrawal is more severe and rapid than natural opioid withdrawal 4

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The Only Safe Transition Protocol

If transitioning from Subutex to naltrexone is clinically indicated (such as moving to extended-release naltrexone for opioid use disorder), the patient must first be completely detoxified from buprenorphine before starting naltrexone. 5, 6

Recommended Transition Approach:

• Stop buprenorphine and wait: The patient must be opioid-free with documented withdrawal symptoms before naltrexone initiation 5
• Timing matters critically: For buprenorphine, wait at least 7-10 days after the last dose before considering naltrexone 5
• Use bridging protocols: The safest approach involves very low-dose naltrexone (starting at 0.25 mg) combined with decreasing doses of buprenorphine over 7 days, with clonidine and ancillary medications to manage withdrawal 5, 6
• Confirm opioid-free status: Perform a naloxone challenge test or confirm negative urine opioid screen before administering naltrexone 1

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Clinical Context: Why This Question Arises

This question typically emerges in two scenarios:

1. Transitioning treatment modalities: A patient stable on Subutex for opioid use disorder may be considered for extended-release naltrexone (Vivitrol) 6
2. Misunderstanding of medications: Confusion between buprenorphine/naloxone combination products (Suboxone) and the separate use of naltrexone 2

Critical Distinction:

• Suboxone = buprenorphine + naloxone: The naloxone in Suboxone is present only to deter IV abuse and is poorly absorbed sublingually 2, 7
• Naltrexone is a completely different medication: It is a pure antagonist used for opioid use disorder maintenance after detoxification, not combined with buprenorphine 1, 5

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Evidence for Successful Transition (When Properly Done)

Research demonstrates that transitioning from buprenorphine to extended-release naltrexone is feasible but requires careful outpatient protocols with very low-dose naltrexone titration. 6

• In one open-label study, 14 of 20 participants (70%) successfully transitioned to extended-release naltrexone using upward titration of very low-dose naltrexone (starting at 0.25 mg) combined with downward titration of buprenorphine over 7 days 6
• The protocol significantly reduced withdrawal discomfort, craving, and drug use compared to baseline 6
• No serious adverse events occurred when the transition was properly managed 6

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Common Clinical Pitfalls

• Never administer naltrexone to a patient currently taking Subutex without proper detoxification—this will cause precipitated withdrawal 1
• Do not confuse the naloxone in Suboxone with naltrexone therapy—these are entirely different clinical scenarios 2
• Avoid rushing the transition—inadequate washout periods lead to precipitated withdrawal and treatment failure 5
• Do not attempt this transition without clonidine and ancillary medications to manage withdrawal symptoms 5, 6

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Bottom Line Algorithm

If a patient is currently taking Subutex:

1. Do not prescribe naltrexone 1
2. If transition to naltrexone is clinically necessary:
   • Taper and discontinue buprenorphine 5
   • Wait 7-10 days minimum 5
   • Use very low-dose naltrexone induction protocol (0.25 mg starting dose) with clonidine support 5, 6
   • Confirm opioid-free status before full-dose naltrexone 1
3. If patient needs ongoing opioid use disorder treatment, continue Subutex—do not switch without compelling clinical reason 6