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Mental Health/Drug Use – Drug-drug Interactions

Drug-Drug interactions


Refer to the Treatment section to view the World Health Organisation (WHO) recommended HAART regimens and management of injecting drug users (IDUs) infected with HIV.

IDUs with HIV take numerous concomitant medications to manage comorbidities and disease manifestations, and clinicians should be aware of the potential for reactions.

Methadone interactions with antiretrovirals

  • Methadone is metabolised in the liver primarily by cytochrome P450 enzymes, particularly CYP3A41
  • When administered concurrently with drugs that inhibit cytochrome enzymes, the level of methadone may increase, requiring dose reduction2
  • Methadone:
    • inhibits the metabolism of zidovudine (ZDV), elevating ZDV levels by as much as 43%3
    • decreases the level of didanosine (ddI) by up to 60%2
  • Nevirapine, efavirenz and ritonavir decrease methadone concentrations and produce opioid withdrawal symptoms2
  • Non-nucleoside reverse transcriptase inhibitors (NNRTIs) are significantly more likely to interact with methadone than protease inhibitors (PIs), as such, IDUs on opioid substitution therapy (OST) require careful monitoring2
  • The PI lopinavir/ritonavir has been shown to produce an increase of methadone metabolism necessitating dosage increases in some cases2

Buprenorphine interactions with antiretrovirals

  • The interactions between buprenorphine and ARVs are less well researched than methadone interactions2
  • Buprenorphine is metabolised in the liver by the cytochrome P450 3A4 enzyme system, therefore other medications that interact with this system should be used with caution2
  • When efavirenz and buprenorphine are co-administered, buprenorphine levels decrease but do not produce a clinical withdrawal2
  • ZDV administered with buprenorphine does not precipitate withdrawals, and ZDV levels do not decrease as they do with methadone2
  • Morphine derivatives and opioid antagonists, such as naltrexone, should not be used with buprenorphine due to its partial antagonist effects2
  • Other potential interactions include:2
    • cytochrome P450 3A4 inhibitors, such as fluconazole and macrolide antibiotics
    • inducers, such as phenobarbital, carbamazepine, phenytoin and rifampicin
    • sedatives, such as benzodiazepines

Methadone interactions with other medications

Interactions between methadone and some medications administered to treat comorbidities such as psychiatric disorders or tuberculosis have been identified in IDUs with HIV2

Download the New York/New Jersey AIDS Education Training Center guide, which presents the interactions between recreational drugs and ART. 

For more information, access the HIV drug interactions website.


  1. Ferrari A, Coccia CP, Bertolini A, Sternieri E. Methadone–metabolism, pharmacokinetics and interactions.  Pharmacol Res 2004;50(6):551–559.
  2. World Health Organization. HIV/AIDS Treatment and Care. Clinical Protocols for the WHO European Region, 2007. Accessed 25 October 2011.
  3. McCance-Katz EF, Rainey PM, Jatlow P, Friedland G. Methadone effects on zidovudine disposition (AIDS Clinical Trials Group 262). J Acquir Immune Defic Syndr Hum Retrovirol 1998;18:435–443.