Hivid Medicine - Information, Side effects and uses of Hivid

Generic Name: Zalcitabine

Hivid is indicated, in combination with zidovudine, for the treatment of HIV infection in patients with limited prior exposure (< 3 months) to zidovudine. Hivid is also indicated, in combination with antiretroviral protease inhibitors, for the treatment of HIV infection. Hivid is indicated as a monotherapy for the treatment of advanced HIV infection in patients who are intolerant of, or who have disease progression while receiving, alternative antiretroviral therapy. The duration of clinical benefit from antiretroviral therapy may be limited. Alterations in antiretroviral therapy should be considered if disease progression occurs during treatment with zalcitabine.

Hivid is phosphorylated by cellular enzymes to its active moiety, 2,3-dideoxycytidine-5-triphosphate (ddCTP). It then competes with the natural substrates for formation of viral DNA by reverse transcriptase, thereby inhibiting viral replication. It also acts as a terminator of chain elongation. In vitro, zalcitabine is approximately 10 times more potent than zidovudine against HIV.

Hivid does not appear to undergo significant metabolism by the liver. The primary metabolite that has been identified is dideoxyuridine (ddU).

Precaution and Warning while taking Hivid

• High doses of zalcitabine administered for 3 months to B 6C 3F 1 mice (resulting in plasma concentrations of over 1000 times those seen in patients taking the recommended doses of zalcitabine) induced an increased incidence of thymic lymphoma.
• No evidence of mutagenicity was found in the Ames test, in the mouse lymphoma cell test, or in the Chinese hamster lung cell test. An unscheduled DNA synthesis assay showed no increases in DNA repair when the assay was performed in rat hepatocytes. However, an in vitro mammalian cell transformation assay was positive at doses of 500 mg per mL and higher. Dose-related increases in chromosomal aberration were seen when human peripheral blood lymphocytes were exposed to zalcitabine, with and without metabolic activation, at concentrations of 1.5 mcg per mL and higher. Oral doses of zalcitabine at 2500 and 4500 mg per kg of body weight (mg/kg) were clastogenic in the mouse micronucleus assay.
• Pregnancy- It is not known whether zalcitabine crosses the placenta. Adequate and well-controlled studies have not been done in pregnant women. Unlike zidovudine, it is not known whether zalcitabine reduces perinatal transmission of HIV infection.
• No information is available on the relationship of age to the effects of zalcitabine in geriatric patients. However, elderly patients are more likely to have an age-related decrease in renal function, which may require a reduction in dose.
• Zalcitabine should be used in pregnancy only if the potential benefit to the mother outweighs the potential risk to the fetus.
• There have been case reports of HIV being transmitted from an infected mother to her nursing infant through breast milk. Therefore, breast-feeding is not recommended in HIV-infected mothers, to avoid potential postnatal transmission of HIV to the nursing infant.
• Safety and efficacy of zalcitabine in combination with zidovudine or as monotherapy have not been fully established in HIV-infected children up to 12 years of age. However, zalcitabine has been both given as a monotherapy and alternated with zidovudine in children 6 months to 12 years of age. Preliminary data show that zalcitabine appears to be well tolerated, and there was clinical improvement and improvement in immunologic and virologic indicators of disease activity. The side effects profile appears to be similar in children and adults.