Peripheral neuropathy zalcitabine causing

NRTls are structural analogues of the natural nucleotides that form the building blocks of RNA and DNA in human cells. Their use as part of HAART has dramatically modified the natural history of HIV infection. They, however, cause a range of drag- or tissue-specific toxicides zidovudine (AZT) causes myopathy zalcitabine (ddC), didanosine (ddl), and lamivudine (3TC) cause neuropathy stavudine (d4T) causes neuropathy or myopathy and lactic acidosis (Dalakas 2001). During phase 1 and 11 trials, the dose-limiting toxicity of didanosine, zalcitabine, and stavudine was identified as peripheral neuropathy (Dalakas 2001). 

This drug is used cautiously in patients with peripheral vascular disease, neuropathy, chronic pancreatitis, or impaired liver function. Didanosine is a Pregnancy Category B drug and is used cautiously during pregnancy and lactation. There may be a decrease in the effectiveness of dapsone in preventing Pneumocystis carinii pneumonia when didanosine is administered with dapsone Use of didanosine with zalcitabine may cause additive neuropathy. Absorption of didanosine is decreased when it is administered with food. 

The use of zalcitabine has been associated with significant clinical adverse reactions, some of which are potentially fatal. Zalcitabine can cause severe peripheral neuropathy therefore, use with extreme caution in patients with pre-existing neuropathy. Zalcitabine may also rarely cause pancreatitis, and patients who develop any symptoms suggestive of pancreatitis while using zalcitabine should have therapy suspended immediately until this diagnosis is excluded. 

Peripheral neuropathy - Patients developing moderate discomfort with signs or symptoms of peripheral neuropathy should stop zalcitabine. Zalcitabine-associated peripheral neuropathy may continue to worsen despite interruption of therapy. Reintroduce the drug at 50% dose (0.375 mg every 8 hours) only if all findings related to peripheral neuropathy have improved to mild symptoms. Permanently discontinue the drug when patients experience severe discomfort related to peripheral neuropathy or moderate discomfort progresses. If other moderate to severe clinical adverse reactions or lab abnormalities (eg, increased liver function tests) occur, interrupt zalcitabine (or both zalcitabine and the other potential causative... 

Zalcitabine should be used with caution in the following patients with a risk of developing peripheral neuropathy Patients with low CD4 cell counts (CD4 less than 50 cells/mm ), diabetes, weight loss, or patients receiving zalcitabine concomitantly with drugs that have the potential to cause peripheral neuropathy. Careful monitoring is strongly recommended for these individuals. 

Zalcitabine therapy is associated with a dose-dependent peripheral neuropathy that can be treatment-limiting in 10-20% of patients but appears to be slowly reversible if treatment is stopped promptly. The potential for causing peripheral neuropathy constitutes a relative contraindication to use with other drugs that may cause neuropathy, including stavudine, didanosine, and isoniazid. Decreased renal clearance caused by amphotericin B, foscamet, and aminoglycosides may increase the risk of zalcitabine neuropathy. The other major reported toxicity is oral and esophageal... 

VASODILATOR ANTIHYPERTENSIVES NNRTIs Risk of peripheral neuropathy when hydralazine is coadministered with didanosine, stavudine or zalcitabine Additive effect both drugs can cause peripheral neuropathy Warn patient to report early features of peripheral neuropathy if it occurs, the NNRTI should be stopped... 

Zalcitabine toxicides are similar to those of the other dideoxynucleotide analogs didanosine and stavudine. Severe peripheral neuropathy has been reported in up to 15% of patients. Pancreatitis occurs rarely with zalcitabine therapy, but coadministration of other drugs that cause pancreatitis should be avoided. One distinctive toxicity of zalcitabine is oral ulceration and stomatitis. An erythematous rash also is common but generally self-limited. The necessity of frequent administration, the risk of toxicides, and the inferior antiviral activity compared to more convenient agents limits the use of zalcitabine in the U.S. 

In vitro, stavudine had no significant effect on the intracellular activation ofzalcitabine. Both stavudine and zalcitabine have the potential to cause peripheral neuropathy and pancreatitis. Combined use of drugs causing these serious adverse effects should be closely monitored (see also NRTIs + Drugs that cause pancreatitis , p.797). US guidelines say that the combination of stavudine and zalcitabine should not be recommended at any time because of additive peripheral neuropathy. ... 

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