Sustiva
Efavirenz
(Both names mean the same drug)

Methadone Interactions

Studies show that Sustiva makes your body clear methadone faster. In trials, 6 out of seven methadone patients on Sustiva relapsed to heroin use!

If you are on methadone and thinking about taking Sustiva, talk to your methadone clinic doctor before you start taking Sustiva, so that she/he is ready to change your dose if you need it!

They studied how much methadone is in people's blood when they are on Sustiva. They used people who were on a stable methadone dose. The methadone in their blood was reduced by 48% (almost half). People needed an average methadone dose increase of 21%.

Does methadone affect Sustiva levels? We don't know, it hasn't been studied.

Feeling methadone withdrawal symptoms on Sustiva?
You should talk to your counselor and your doctor. Chances are that you need your dose raised to compensate for the Sustiva. But there may be other factors: what other HIV meds are you taking? You need to know about the side effects for ALL your meds, and your doctor should know them too!

This section is taken from: Gourevitch MN (MD), Friedland GH (MD) Interactions between Methadone and Medications Used to Treat HIV Infection: A Review Mount Sinai Journal of Medicine, October/November 2000. This review summarizes currently available information on methadone interactions with HAART drugs. Studies cited in these quotations are cited here as well at the bottom of this page

"Methadone undergoes hepatic biotransformation by the cytochrome P450 system. Two cytochrome P450 isoenzymes, CYP 3A4 and CYP 2D6, appear to be primarily involved in this process, with CYP 2C possibly playing a minor role as well (7, 8). ..."

"By way of contrast [with NRTIs], the non-nucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors (PIs) share metabolic pathways with methadone, leading to the possibility that important interactions might occur between methadone and these medications. NNRTIs have complex interactions with the cytochrome P450 system. ... Efavirenz both induces and inhibits CYP 3A4, and is metabolized in vitro by CYP 3A4 and CYP 2136 (16)."

"A recently presented and similarly retrospective case series offers evidence suggesting that, as with nevirapine, initiation of an efavirenz-containing antiretroviral regimen also necessitated increased methadone doses in most patients (27). In this study, nine methadone-maintained patients were followed after initiation of antiretroviral therapy. Seven of the nine patients were taking efavirenz-containing regimens, and six of these (87%) had a resumption of heroin use that resulted in a methadone dose increase, presumably in response to efavirenz-induced withdrawal symptoms. Such findings underscore the clinical urgency of recognizing interactions of this and other medications with methadone.

"Further evidence of an efavirenz-methadone interaction derives from the pharmacokinetic data presented by Clarke and colleagues (26). Fifteen dose-stabilized methadone maintenance patients were started on antiretroviral therapy with efavirenz and two nucleosides. From baseline to three weeks following efavirenz initiation, mean methadone peak plasma concentration and AUC decreased by 48% and 57%, respectively. Of the 25 patients begun on nevirapine or efavirenz-containing regimens presented by-Clarke et al., 17 (68%) complained of narcotic withdrawal symptoms, necessitating a mean increase in methadone dose of 21 %."

"It is now known that interactions occur between methadone and some HIV-related medications, yet their characteristics cannot reliably be predicted based on current understanding of enzyme induction and/or inhibition, or through in vitro studies. Carefully designed studies using human subjects are urgently needed. Until more data are available, clinicians are left to rely on their best judgment when selecting regimens and when clinical evidence of possible interactions arises in the course of patient care. As always, much is gained from listening to the patient. If a methadone-maintained patient recently started on HIV-related medication, particularly an NNRTI, describes withdrawal symptoms, and no other reason for such symptoms is evident, an empiric trial of raising the methadone dose may be an appropriate response. Methadone dose increases should be in 10-mg increments. If marked withdrawal is present and attributable to a medication interaction in a previously stable methadone-maintained patient, an incremental increase of 20 mg may be considered. To avoid overdosing, however, methadone should not be increased more frequently than every two to three days. Alternatively, use of a different antiretroviral agent might be warranted. Obtaining a trough methadone level to establish whether withdrawal symptoms are indeed due to increased methadone metabolism may be useful in selected cases, particularly if continuation of an HIV therapeutic regimen is deemed necessary."

Studies cited in the above quotations:

7. Iribarne C, Berthou F, Baird S, et al. Involvement of cytochrome P450 3A4 enzyme in the N-demethylation of methadone in human liver microsomes. Chem Res Toxicol 1996; 9:365-373.

8. Wu D, Otton SV, Sproule BA, et al. Inhibition of cytochrome P450 2D6 (CYP2 D6) by methadone. Br J Clin Pharmac 1993; 3 5:3 0 - 34.

16. Sustiva Product Information. DuPont Pharmaceuticals. Wilmington (DE). 1998.

26. Clarke S, Mulcahy F, Back D, et al. Managing methadone and non-nucleoside reverse transcriptase inhibitors: Guidelines for clinical practice. Seventh Conference on Retroviruses and Opportunistic Infections, 2000 Jan 30 - Feb 2; San Francisco, CA. Abstract No. 88.

27. Tashima K, Bose T, Gormley J, et al. The potential impact of efavirenz on methadone maintenance, Ninth European Congress of Clinical Microbiology and Infectious Diseases; 1999 Mar2l -24; Berlin, Germany. AbstractNo. P0552.