Zidovudine - Side Effects

Side Effects

AZT-based antiretroviral therapy has been proven to significantly reduce rates of certain AIDS-defining cancers (most dramatically, that of Kaposi's sarcoma and central nervous system lymphoma).

Early long-term higher-dose therapy with AZT was initially associated with side effects that sometimes limited therapy, including anemia, neutropenia, hepatotoxicity, cardiomyopathy, and myopathy. All of these conditions were generally found to be reversible upon reduction of AZT dosages. They have been attributed to several possible causes, including transient depletion of mitochondrial DNA, sensitivity of the γ-DNA polymerase in some cell mitochondria, the depletion of thymidine triphosphate, oxidative stress, reduction of intracellular L-carnitine or apoptosis of the muscle cells. Anemia due to AZT was successfully treated using vitamins to stimulate red blood cell production. Drugs that inhibit hepatic glucuronidation, such as indomethacin, nordazepam, acetylsalicylic acid (aspirin) and trimethoprim, decreased the elimination rate and increased the therapeutic strength of the medication. Most common side-effects included upset stomach and acid reflux (heartburn), headache, cosmetic reduction in abdominal body fat, light sleeping, and occasional loss of appetite; while less-common complaints included faint discoloration of fingernails and toenails, mood elevation, occasional tingling or transient numbness of the hands or feet, and minor skin discoloration. Allergic reactions were rare. Today, side-effects are much less common with the use of lower doses of AZT. According to IARC, there is sufficient evidence in experimental animals for the carcinogenicity of zidovudine; it is possibly carcinogenic to humans (Group 2B).

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