Taking methadone with prescribed drugs, including anti-HIV drugs can have a number of different effects. Some doctors are taking a cautious approach to antiretroviral treatment among people who are also taking drugs such as anti-depressants, stimulants or opiates, possibly admitting them to hospital for observation when treatment is first started.

Drugs which are likely to decrease methadone levels.

Of the NNRTI anti-HIV drugs, nevirapine is likely to decrease methadone levels. A study in Dublin reported that nevirapine reduced methadone levels by 46% within two to three weeks of commencing the drug. Patients began to report opiate withdrawal symptoms 8-10 days after starting, however it is not recommended that methadone dosage be increased at the same time as starting nevirapine. Instead, it may be better to monitor withdrawal symptoms and increase the methadone dose if withdrawal does begin to occur (Clarke 2000).

The NNRTI efavirenz reduces exposure to methadone by about 60% within 24 hours of commencing (Marzolini et al. 2000). This occurs because efavirenz speeds up, or induces, the metabolism of methadone. However, dosage adjustment should not take place immediately because the neurological side-effects of efavirenz may be mistaken for opiate withdrawal. As with nevirapine, close monitoring for withdrawal is recommended. Gradual dose increases of methadone are advised if symptoms of withdrawal occur.

The nucleoside reverse transcriptase inhibitor (NRTI) stavudine (d4T) has been shown to reduce methadone levels by about 25%. Again, an individual should be monitored for withdrawal symptoms, and dose of methadone increased if necessary.

Drugs which are likely to increase methadone levels

On the basis of the liver metabolism if both saquinavir and methadone are taken together then levels of both drugs might increase and so dose reductions may be necessary.

Of the NNRTI anti-HIV drugs, delavirdine is likely to substantially increase levels of methadone, so dose reductions may be necessary.

Merck is currently conducting a formal study of indinavir and methadone. The company suggests that on the basis of their liver metabolism, levels of both drugs might increase and so dose reductions may be necessary.

No effect on methadone level

There has been very little research into interactions between methadone and other nucleoside analogues such as ddI (didanosine), ddC (zalcitabine) and 3TC (lamivudine), although no problems have been reported with combining these drugs.

Drugs with mixed / contradictory effects

Ritonavir has been shown to increase the potency of methadone when studied in the test tube but in real life it seems to have the opposite effect.

Effect of methadone on HAART medication

Methadone maintenance affects the metabolism of numerous antiviral medications commonly prescribed in HIV-positive individuals including NRTIs such as zidovidine, stavudine, didanosine and abacavir as well as NNRTIs such as efaverinz and nevirapine.

Levels of ddI (didanosine) in the blood of methadone users were only 60% of those observed in ddI users not receiving methadone. Methadone delayed the absorption of ddI, which could be a problem because the drug is not stable and the part of the ddI that does not get absorbed quickly can be damaged by stomach acid and, possibly, digestive enzymes. A larger dose may be needed.

Methadone has been found to increase AZT levels twofold. Very high levels of AZT in your system can mimic the early symptoms of opiate withdrawal. Reducing methadone dosages does not make the side-effects of AZT less severe.