How many days after taking one buprenorphine (Suboxone) pill can a patient start taking naltrexone (Narcan)?

Waiting Period After Buprenorphine Before Starting Naltrexone

You must wait a minimum of 7-10 days after taking one buprenorphine pill before starting naltrexone to avoid precipitating severe, potentially life-threatening withdrawal. 1

FDA-Mandated Opioid-Free Interval

• The FDA drug label explicitly requires patients to be completely opioid-free for a minimum of 7-10 days for short-acting opioids before initiating naltrexone. 1
• Buprenorphine, despite being a partial agonist, requires the same 7-10 day washout period as other opioids. 1
• Patients transitioning from buprenorphine may be vulnerable to precipitation of withdrawal symptoms for as long as 2 weeks, and healthcare providers should be prepared to manage withdrawal symptomatically with non-opioid medications. 1

Critical Risk of Precipitated Withdrawal

• Administering naltrexone to patients with recent opioid exposure (including buprenorphine) can precipitate severe, potentially life-threatening withdrawal requiring hospitalization. 1
• The FDA warns that postmarketing case reports have documented severe manifestations of precipitated withdrawal when switching from buprenorphine to naltrexone. 1
• Starting naltrexone too early after buprenorphine can precipitate severe withdrawal because naltrexone blocks opioid receptors as a competitive antagonist, and any residual buprenorphine will be displaced from receptors. 2

Verification Before Naltrexone Initiation

• Before starting naltrexone, perform a naloxone challenge test to confirm the patient is adequately opioid-free. 1
• The naloxone challenge should not be performed in patients showing clinical signs of opioid withdrawal or whose urine contains opioids. 1
• For intravenous challenge: inject 0.2 mg naloxone, observe for 30 seconds, then inject 0.6 mg if no withdrawal signs appear, and observe for an additional 20 minutes. 1
• For subcutaneous challenge: administer 0.8 mg naloxone and observe for 20 minutes for signs of withdrawal (nausea, vomiting, sweating, pupillary dilation, anxiety, muscle aches). 1
• If the naloxone challenge is positive (withdrawal signs appear), do not initiate naltrexone and repeat the challenge in 24 hours. 1

Clinical Algorithm

• Confirm the patient's last dose of buprenorphine was at least 7-10 days ago. 1
• Verify the patient has no clinical signs of opioid withdrawal and no opioids in urine. 1
• Perform a naloxone challenge test to confirm adequate opioid-free status. 1
• If the challenge is negative, initiate naltrexone at 25 mg on day 1, then increase to 50 mg daily if no withdrawal occurs. 1
• If the challenge is positive, wait an additional 24 hours and repeat the challenge before attempting naltrexone initiation. 1

Common Pitfall to Avoid

• The most dangerous error is assuming buprenorphine's partial agonist properties allow for a shorter waiting period—they do not. 1
• Buprenorphine has a long half-life and high receptor affinity, making precipitated withdrawal particularly severe if naltrexone is started prematurely. 1
• Extended-release naltrexone formulations require an even longer washout period of 24-30 days after the last injection if the patient later needs to restart buprenorphine. 3, 2