Adjusting methadone dosage on efavirenz: how much and when to do it

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Methadone dosage may need to be increased by around 22% a week after starting efavirenz treatment, according to Dr Fiona Mulcahy of St James's Hospital, Dublin.

Elaborating on data first presented at the Seventh Conference on Retroviruses and Opportunistic Infections, Dr Mulcahy told a British HIV Association conference satellite meeting organised by Du Pont Pharma that efavirenz reduced methadone exposure (AUC) by an average of 60% within 24 hours of the first efavirenz dose.

This occurs because efavirenx speeds up, or induces, the metabolism of methadone. However, dosage adjustment should not take place immediately.

Glossary

withdrawal

In the context of drugs or alcohol, withdrawal is when a person cuts out, or cuts back, on using the substance, also known as detoxification or detox. In a context of sexual risk reduction, it refers to the insertive partner in penetrative sex withdrawing before ejaculation. It is not a particularly effective way to lower the risk of HIV transmission or pregnancy.

neurological

Relating to the brain or central nervous system.

metabolism

The physical and chemical reactions that produce energy for the body. Metabolism also refers to the breakdown of drugs or other substances within the body, which may occur during digestion or elimination.

"Complaints about withdrawal symptoms during days one to three of efavirenz treatment are more likely to be connected with the neurological effects of efavirenz. The induction effect of efavirenz tends to build up over a week or more, so there will not be an immediate reduction in methadone levels" said Dr Mulcahy.

The methadone dose increase required will depend on the existing methadone dose. People taking high doses of methadone will need correspondingly larger increases in their methadone script, which should be built up day by day as soon as withdrawal effects begin to be noticed. In her Dublin clinic, Dr Mulcahy has been increasing dosages by 10mg at a time until withdrawal symptoms stop.

Methadone levels need to be reduced again if efavirenz treatment stops for any reason, and the dose reduction will need to be tapered over 8-10 days to avoid withdrawal symptoms.