Deoxycytidine nucleoside analogue
| Clinical Use|
There is little evidence from large-scale trials for the effectiveness of triple-antiretroviral combinations including zalcitabine.
Zalcitabine and didanosine should not be used in combination because of their overlapping potential side effects of peripheral neuropathy and pancreatitis, their similar resistance profiles, and the lack of demonstrated efficacy of this combination. Zalcitabine and stavudine should not be used together because of the overlapping side effect of peripheral neuropathy. Patients receiving zalcitabine together with other potentially neurotoxic drugs (such as isoniazid or vincristine) should be monitored closely for the development of neuropathic symptoms.
| Use in Initial vs Subsequent Therapy|
Treatment guidelines of the U.S. Department of Health and Human Services do not consider zalcitabine to be a "preferred," "alternative," or "acceptable" component for initial treatment of HIV infection. The guidelines recommend against using the combination of zalcitabine and either didanosine or stavudine because of additive toxicity. They also recommend against using zalcitabine + lamivudine because of adverse drug interactions, or zalcitabine + zidovudine, because of limited antiviral activity.
Few data are available regarding the effectiveness of zalcitabine outside initial combination therapies. Two large studies (2,3) found no advantage in survival or disease progression when patients previously treated with zidovudine monotherapy added zalcitabine.
| Factors Affecting Adherence|
Symptomatic side effects of zalcitabine include peripheral neuropathy, which is common and may be disabling. Zalcitabine should be avoided in individuals with previously existing peripheral neuropathy. Other side effects that may affect adherence include mucosal ulcerations and rash.
There is evidence that nucleoside analogues may be associated with mitochondrial toxicity leading to potentially serious long-term side effects such as lactic acidosis and disorders of lipid metabolism. Compared with other nucleoside analogues, zalcitabine appears to be a relatively potent inhibitor of mitochondrial DNA polymerase in vitro.(4) The clinical implications of this observation are unclear.
|| ||Follansbee S, Drew L, Olson R, et al. The efficacy of zalcitabine (ddC, Hivid) versus zidovudine (ZDV) as monotherapy in ZDV-naive patients with advanced HIV disease; a randomized, double-blind, comparative trial (ACTG 114; N3300). Abstract PO-B26-2113. IXth International Conference on AIDS, June 7-11, 1993; Berlin.|
|| || Delta: a randomised double-blind controlled trial comparing combinations of zidovudine plus didanosine or zalcitabine with zidovudine alone in HIV-infected individuals. Delta Coordinating Committee. Lancet 1996;348:283-91.|
|| || Katzenstein DA, Hammer SM, Hughes MD, Gundacker H, Jackson JB, Fiscus S, Rasheed S, Elbeik T, Reichman R, Japour A, Merigan TC, Hirsch MS. The relation of virologic and immunologic markers to clinical outcomes after nucleoside therapy in HIV-infected adults with 200 to 500 CD4 cells per cubic millimeter. AIDS Clinical Trials Group Study 175 Virology Study Team. N Engl J Med 1996;335:1091-8.|
|| || Kakuda TN. Pharmacology of nucleoside and nucleotide reverse transcriptase inhibitor-induced mitochondrial toxicity. Clin Ther 2000;22:685-708.|