Naltrexone, an opioid antagonist, is a proven treatment for Opioid Use Disorder (OUD) and Alcohol Use Disorder (AUD). It works by occupying opioid receptors. This means that opioids and alcohol cannot create the feelings of euphoria they are associated with; thus, reducing cravings for them. 

On the other hand, some medications relieve pain by activating opioid receptors and triggering the release of feel-good hormones (endorphins) in the brain and nervous system. Understandably, these medications do not work if Naltrexone is already in the system

While pain management is beyond the scope of practice at Confidant Health, in this article, our experts discuss research-backed pain medications that may be able to help with pain while on Naltrexone. However, always consult your healthcare provider before taking any pain medication. 

Pain Medications you can Take with Naltrexone: An Overview


Pain Medications that can be Taken with Naltrexone

Pain is the most common cause for doctors visits worldwide. This is unsurprising given the many causes of pain:

  • Mechanical injuries to the skin

  • Contact with allergens 

  • Joint injuries

  • Chemical inflammation

  • Contact with chemical irritants

  • Distension of internal organs

  • Damage to internal organs 

  • Strenuous muscle exertion 

If you are experiencing pain, here is a list of pain medication (in order of increasing strength) that you can safely take with Naltrexone:

Acetaminophen (Paracetamol)

Acetaminophen is a safe, non-opioid analgesic medication. It relieves pain by inhibiting the release of prostaglandins (chemicals that produce the sensation of pain).

Acetaminophen works best for mild to moderate pain relief. For example, studies show single doses of acetaminophen can adequately reduce perineal pain in women after they have given birth. Similarly, another systematic review shows acetaminophen can lower requirements for opioids (and other rescue analgesics) following major surgeries. 

Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)

NSAIDs relieve pain by blocking the production of pain causing chemicals (prostacyclins, thromboxanes, and prostaglandins) in the nervous system.

While NSAIDs can relieve any type of pain, they are particularly effective for joint aches. In addition, studies show they can reduce post-op pain in up to 30% of patients, if administered before a major surgery.

Topical analgesics

Topical analgesics are a broad category of analgesics that can help relieve pain in specific areas. Here’s how they work:

  • Topical rubefacients dilate blood vessels by irritating nerves in the skin. This disrupts the transmission of pain signals.

  • Topical capsaicin inhibits the production of substance P, a chemical that transmits pain. Studies show that a single capsaicin patch can relieve post-surgical nerve pain for up to three months. 

  • Topical lidocaine, an anesthetic agent, reduces sensitivity to pain by suppressing movement of chemicals between cells. Studies show it can relieve postoperative pain in up to 68% of patients. 


Doctors can use antidepressants, off-label, to relieve pain. For example, studies show tricyclic antidepressants (TCAs) can effectively relieve nerve pain due to nerve compression, diabetes, or herpes infections. Similarly, other research shows TCAs can also reduce the frequency of migraines and tension headaches by up to 75%

TCAs, like other antidepressants, work by inhibiting the removal of feel-good hormones (such as serotonin and norepinephrine) at nerve endings. This promotes feelings of well-being and relieves pain.

Anti-Seizure Medicines

Like antidepressants, doctors can also prescribe anti-seizure medications, off-label, to treat migraines and nerve pain. These medications relieve pain by inhibiting the transmission of pain signals between nerve cells. 

Studies show that gabapentin (an anti-seizure medication) can relieve nerve pain in up to 38% of individuals. 


Clonidine is FDA-approved for management of cancer-related pain (and high blood pressure). It reduces pain by activating alpha adrenergic receptors in the spinal cord, which, in turn, lowers pain transmission.  

Studies show clonidine can also reduce post-operative pain. For example, the use of clonidine, in children undergoing eye surgeries, reduced analgesic requirements by 79%. Similarly, clonidine reduced pain by up to 50% in 12 out of 13 patients who underwent a lung-reduction surgery. 


Ketamine is a general anesthetic that can relieve pain. It works by blocking N-methyl-D-aspartate (NMDA) receptors and glutamate receptors in the brain. This lowers the brain’s ability to perceive pain.

Doctors use low-dose ketamine, off-label, to treat:

How to Manage Pain with Naltrexone after a Planned Surgery?

Pain management in patients on Naltrexone that are due to undergo surgery can be challenging for two main reasons:

  • Ineffectiveness of opioid analgesics while on Naltrexone

  • The risk of discontinuation of Naltrexone (i.e., relapse)

Given the unique situation of every individual, we can not make broad recommendations here. Thus, you should always consult a licensed healthcare provider, about the best way to manage your pain before a planned surgery.    

What Medications Should not be Taken with Naltrexone?

Here is a list of medications you should not take with Naltrexone:

Opioids and Alcohol

Patients should be off opioids and alcohol for at least 7 days before starting Naltrexone. This is because Naltrexone can dislodge opioids and endorphins from their receptors, causing withdrawal. 

On the other hand, users may be compelled to use large doses of opioids to bypass Naltrexone’s effect. This raises the risks of serious injury, overdose, coma, and death. 

Opioid Analgesics

Naltrexone is an opioid antagonist; thus, opioid analgesics may be ineffective.

Cough and Cold Remedies

Cold and cough remedies are opioid-containing medications. Thus, they may be ineffective in patients already on Naltrexone (an opioid antagonist).

Antidiarrheal Medication

Anti-diarrheal medications also contain opioids and may be ineffective if used with Naltrexone.  


Disulfiram is a medication that discourages alcohol use. However, using it together with Naltrexone increases the risk of liver problems


Thioridazine, although no longer available, is an antipsychotic medication used to treat schizophrenia. Combined use of thioridazine and Naltrexone can lead to increased plasma levels of thioridazine, which can cause severe lethargy. 

Frequently Asked Questions About Naltrexone and Pain Medications

Does Naltrexone (Vivitrol) Help with Pain?

Studies show low-dose Naltrexone can help relieve the pain of conditions such as chronic fatigue syndrome and fibromyalgia.

Can You Take Naltrexone and Oxycodone at the Same Time?

Oxycodone is a semi-synthetic opioid. So it may be ineffective when taken with Naltrexone. 

Does Naltrexone Block Ibuprofen?

Naltrexone does not block the effects of ibuprofen (an NSAID)

Can you Take Tylenol with Naltrexone?

Tylenol is safe to use with Naltrexone in healthy individuals. But please consult a healthcare professional before taking any medication. 

Can you Take Tramadol with Naltrexone?

Tramadol is an opioid pain medication, so it may be ineffective when taken with Naltrexone.

Can Naltrexone and Benadryl be Taken Together?

You can take Naltrexone and Benadryl together. However, you should always consult your healthcare provider before taking any medication.  

Does Naltrexone Block Muscle Relaxers?

Naltrexone does NOT block the action of muscle relaxers. 

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