Methadone Interferes With Some Formulations of ddI

Methadone is a drug used to help people addicted to heroin and other opiates manage their addiction. Doctors at Yale University have been conducting experiments on methadone users who are also taking the anti-HIV drugs ddI (Videx) and d4T (Zerit). According to their results, methadone significantly reduced the amount of ddI that was absorbed from the digestive tract into the blood.

Researchers reported results from 27 subjects (12 female, 15 male), about half of whom had HIV infection. All subjects had been taking a stable dose of methadone for three weeks prior to entering the study. Subjects took 200 mg of ddI twice daily or 40 mg of d4T twice daily for a few days. The first daily dose of antiviral medication was also taken with the daily dose of methadone. Nurses observed subjects taking the study medication.

The researchers found that levels of ddI in the blood of methadone users were only about 60% of those observed in ddI users not receiving methadone. As well, the maximum level of ddI in methadone users was only about 66% of that seen in non-methadone users. With regard to d4T levels, the researchers found that methadone reduced d4T levels by about 25%. Neither ddI nor d4T affected methadone levels, and the research team did not measure CD4+ cell counts or viral load during this study.

The study also revealed that methadone delayed the absorption of d4T and ddI. In the case of d4T, this delay is likely not a serious problem because the drug is relatively stable and most of it is eventually absorbed, which is not the case with ddI however. In fact, the part of ddI that does not get absorbed quickly can be damaged by stomach acid and, possibly, digestive enzymes.

The researchers state that their findings "suggest a need for a larger dose of ddI," if the currently available tablet formulation is used by people being treated with methadone. As an alternative, the buffered liquid formulation of ddI may be an option because the liquid tends to move out of the stomach, where the risk of damage to ddI is greatest. Although the buffered liquid formulation is not sold in Canada, powdered ddI is available. This form of ddI can be mixed with water and an antacid such as Mylanta or Maalox by a pharmacist. When stored in a refrigerator, this liquid form of ddI may be kept for up to 30 days. The manufacturer of ddI is developing a special coating for ddI that should protect the drug from stomach acid. Studies of the interaction between methadone and other forms of ddI are being reviewed by the Yale research team.

Journal of Acquired Immune Deficiency Syndromes 2000;24:241-248.