Why can't you take opiates (opioid agonists) with naltrexone (opioid antagonist)?

From the Guidelines

You should not take opiates while on naltrexone because it can lead to serious health risks, including respiratory depression and overdose, as well as precipitated withdrawal symptoms. Naltrexone is an opioid antagonist that binds to the same receptors in the brain that opioids target, but instead of activating these receptors, it blocks them 1. If you take opioids while on naltrexone, you won't feel their pain-relieving or euphoric effects. More dangerously, if you try to overcome this blockade by taking higher doses of opioids, you risk serious respiratory depression and overdose when the naltrexone wears off. Additionally, if you have opioids in your system when starting naltrexone, you can experience precipitated withdrawal—a sudden, severe onset of withdrawal symptoms.

Some key points to consider when taking naltrexone include:

• Naltrexone cannot be used in patients who require opioids for pain control, as it will block pain relief from opioid agonists and cause withdrawal symptoms 1
• Patients typically need to be opioid-free for 7-10 days before starting naltrexone to avoid precipitated withdrawal symptoms
• If you're prescribed naltrexone for alcohol use disorder or opioid use disorder, it's crucial to inform all healthcare providers about this medication to prevent dangerous drug interactions
• Naltrexone-bupropion ER, a combination medication, should not be used in patients who require short-term or long-term opiate therapy, as it can reduce the efficacy of the analgesic or precipitate a withdrawal reaction 1

It's essential to follow the recommended guidelines and consult with a healthcare provider before taking any medication, especially when it comes to opioid antagonists like naltrexone. The most recent study on this topic, published in 2022, highlights the importance of careful consideration when using naltrexone-bupropion ER, especially in patients with a history of opioid use or those who require opioid therapy for pain management 1.

From the FDA Drug Label

Naltrexone hydrochloride is contraindicated in Patients receiving opioid analgesics. Patients currently dependent on opioids, including those currently maintained on opiate agonists (e.g., methadone ) or partial agonists (e.g., buprenorphine) In a situation requiring opioid analgesia, the amount of opioid required may be greater than usual, and the resulting respiratory depression may be deeper and more prolonged. Patients on naltrexone hydrochloride may not experience the expected effects from opioid-containing analgesic, antidiarrheal, or antitussive medications. Advise patients that because naltrexone hydrochloride can block the effects of opioids, patients will not perceive any effect if they attempt to self-administer heroin or any other opioid drug, in small doses while on naltrexone hydrochloride Further, emphasize that administration of large doses of heroin or any other opioid to try to bypass the blockade and get high while on naltrexone hydrochloride, may lead to serious injury, coma., or death.

You can't take opiates with naltrexone because naltrexone is an opioid antagonist that blocks the effects of opioids. Taking opiates with naltrexone can lead to:

• Precipitation of opioid withdrawal in patients who are dependent on opioids
• Increased sensitivity to opioids after naltrexone treatment is discontinued or temporarily interrupted, which can increase the risk of accidental overdose
• Serious injury, coma, or death if large doses of opioids are taken to try to bypass the blockade
• Reduced efficacy of opioid-containing medications, such as cough and cold preparations, antidiarrheal preparations, and opioid analgesics 2, 2, 2

From the Research

Opiate and Naltrexone Interaction

• Naltrexone is a competitive opioid receptor antagonist that blocks the euphoric effects of exogenous administered opioids 3.
• When used in opioid-dependent patients, naltrexone can cause acute and severe withdrawal symptoms, including agitation, altered level of consciousness, nausea, vomiting, and abdominal pain 3.
• The administration of naltrexone to patients who are physically dependent on opioids can precipitate a withdrawal syndrome, which can be severe and difficult to manage 4, 5.

Mechanism of Action

• Naltrexone binds tightly to μ-opioid receptors and blocks the subjective and analgesic effects of opioids 5.
• The use of opioid antagonists, such as naltrexone, can induce withdrawal in opioid-dependent individuals, and this withdrawal can be more intense than withdrawal managed with other approaches 6.

Consequences of Co-Administration

• Taking opiates with naltrexone can lead to severe withdrawal symptoms, as naltrexone blocks the effects of opioids and can precipitate a withdrawal syndrome 3, 4.
• The co-administration of opiates and naltrexone is not recommended, as it can lead to adverse effects, including vomiting, diarrhea, and delirium 6.

Clinical Implications

• Patients who are physically dependent on opioids should not be given naltrexone until they have been detoxified, as this can help to reduce the risk of severe withdrawal symptoms 5.
• The use of naltrexone in the treatment of opioid dependence requires careful consideration and monitoring, as it can have significant consequences, including the precipitation of withdrawal symptoms 3, 4.