Zalcitabine drug interactions

Drug interactions Vitravene is not recommended for use in patients who have recently (2-4 weeks) been treated with either intravenous or intravitreal cidofovir because of the risk of exaggerated ocular inflammation. Results from in vitro tests demonstrated no inhibition of anti-CMV activity of fomivirsen by zidovudine or zalcitabine. 

Potential drug interactions include an increased AUC of zalcitabine when administered in combination with probenecid or cimetidine and decreased bioavailability when zalcitabine is coadministered with antacids or metoclopramide. Lamivudine inhibits the phosphorylation of zalcitabine in vitro, potentially interfering with its efficacy. 

Drugs that may interact with lamivudine include zalcitabine and trimethoprim/sulfamethoxazole. 

Drugs that may interact with zalcitabine include antacids, chloramphenicol, cisplatin, dapsone, didanosine, disulfiram, ethionamide, glutethimide, gold, hydralazine, iodoquinol, isoniazid, metronidazole, nitrofurantoin, phenytoin, ribavirin, vincristine, cimetidine, metoclopramide, amphotericin, aminoglycosides, foscarnet, antiretroviral nucleoside analogs, pentamidine, and probenecid. 

Buffering agents that are compounded with didanosine to counteract its degradation by gastric acid may interfere with the absorption of other drugs that require acidity (e.g., indinavir, delavirdine, ketoconazole, fluoroquinolones, tetracyclines, dapsone). An enteric-coated formulation Videx EC) that dissolves in the basic pH of the small intestine is not susceptible to these interactions. Ganciclovir and valganciclovir can increase blood levels of didanosine. The use of zalcitabine with didanosine is not recommended because that combination carries an additive risk of peripheral neuropathy. The combination of didanosine with stavudine increases the risk of pancreatitis, hepatotoxicity, and peripheral neuropa-... 

Zalcitabine does not interact with zidovudine, and lamivudine inhibits its phosphorylation. It should not be administered with other drugs that cause neuropathy or pancreatitis including didanosine and stavudine. 

Foscamet sodium should not be mixed with any intravenous infusion drug, since it interacts with glucose- and calcium-containing solutions and sodium, ganciclovir, certain antibacterials, amphotericin, pentamidine isethionate, and trimetrexate.18 Care must be taken to avoid inhalation and exposure of the skin to zalcitabine powder. 

Lamivudine inhibits the intracellular phosphorylation of zalcitabine and antagonizes zalcitabine s antiretroviral activity in vitro, although the clinical significance of this interaction is unknown. Probenecid increases the zalcitabine AUC by about 50%, probably through inhibition of tubular secretion cimetidine increases the AUC by 36% via an unknown mechanism. Zalcitabine should be avoided in patients with a history of pancreatitis or neuropathy because the risk and severity of both complications increase. Coadministration of other drugs that cause pancreatitis or neuropathy also will increase the risk and severity of these symptoms. Ethambutol, isoniazid, vincristine, cisplatin, and pentamidine, as well as the antiretroviral drugs didanosine and stavudine, therefore, should be avoided. 

NRTIs are water soluble, and are mainly eliminated by the kidneys (di-danosine, lamivudine, stavudine, and zalcitabine) or undergo hepatie glu-curonidation (abacavir, zidovudine). The few important interactions with these drugs primarily involve altered renal clearance. For zidovudine (and possibly abacavir) some interactions occur via altered glucuronidation, but the clinical relevance of these are less clear (e.g. rifampicin , (p.792)). Cytochrome P450-mediated interactions are not important for this class of drugs. 

Clarithromycin causes some reduction in the bioavailability of zidovudine, but this is minimised if the two drugs are given at least 2 hours apart. Clarithromycin does not appear to interact with didanosine, stavudine or zalcitabine, and azithromycin does not interact with didanosine or zidovudine. 

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