The European Medicines Agency has issued new guidance on the use of d4T (stavudine, Zerit), saying that the drug should be used only when no other alternative option exists, due to its toxicity.
The agency’s Committee for Medicinal Products for Human Use (CHMP) also says that when the drug must be used, it should be used for the shortest time possible.
The decision was taken after a review of safety information as part of a marketing re-authorisation.
The drug has several well-established side effects that are either life-threatening or may cause serious long-term harm. These are:
- Lactic acidosis (a build-up of lactic acid in the body), which may lead to death if not treated early enough.
- Peripheral neuropathy (damage to the nerves in the limbs, especially the feet and legs), which may be irreversible in some patients. It leads to pain and difficulty in walking.
- Lipoatrophy (subcutaneous fat loss, especially in the limbs, buttocks and face) which is usually irreversible except through reparative surgery. Patients find the loss of fat highly disfiguring and stigmatising.
Each side-effect is linked to long-term use of d4T, and each side-effect has been known about for at least a decade.
The use of d4T in first-line treatment was abandoned in the United States and Europe after head-to-head comparisons with AZT and with tenofovir-containing regimens showed that patients who received d4T were more likely to suffer lipoatrophy.
The World Health Organization has also issued a series of treatment guideline revisions intended to discourage the use of d4T in resource-limited settings. The drug continues to form part of first-line antiretroviral drug combinations in many countries due to its low cost in comparison to tenofovir.
The agency says that all patients taking the drug in the European Union should be reviewed regularly and switched at the earliest opportunity to another drug.