Zalcitabine pancreatitis with

Additive pancreatic toxicity has been described with zalcitabine and intravenous pentamidine, and is expected when didanosine or stavudine are given with other drugs that can cause pancreatitis. An isolated case describes pancreatitis with lamivudine and aza-thioprine. 

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. 

Zalcitabine (ddC) Hivid (anticipated discontinuation of distribution in 2006) 0.375-, 0.75-mg tab 0.75 mg tid CrCI Dose (mL/minute) 10-40 0.75 mg bid less than 10 0.75 mg qday No data on hemodialysis None Peripheral neuropathy stomatitis, lactic acidosis with hepatic steatosis (rare but potentially life-threatening toxicity with use of NRTIs) pancreatitis Renal excretion... 

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. 

Combination therapy - For toxicities likely to be associated with zalcitabine (eg, peripheral neuropathy, severe oral ulcers, pancreatitis, elevated liver function tests, especially in patients with chronic hepatitis B see Warnings and Precautions), interrupt or reduce dose. For severe toxicities or those persisting after dose reduction, interrupt zalcitabine therapy. For recipients of combination therapy with zalcitabine and other antiretrovirals, base dose adjustments or interruption for either drug on the known toxicity profile of the individual drugs. 

Pancreatitis Pancreatitis, fatal in some cases, has been observed with zalcitabine administration. Pancreatitis is an uncommon complication of zalcitabine therapy, occurring in up to 1.1% of patients. 

As a class effect NRTIs are associated with lactic acidosis and hepatic steatosis, conditions which may occur more frequently in pregnant women. The individual NRTIs have their own adverse reactions. Pancreatitis is seen with lamivudine, stavudine, di-danosine and rarely with zalcitabine while the latter three agents can also induce peripheral neuropathy. 

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-... 

Lamivudine is associated with an increased risk of pancreatitis in children and should be used with great caution in children who have had pancreatitis or are at high risk for it. Dosage adjustment is necessary in patients with renal impairment. Lamivudine should not be used in combination with zalcitabine, because they inhibit each other s activation by phosphorylation. Trimethoprim inhibits the renal elimination of lamivudine. 

Peripheral neuropathy occurs in up to 50% of patients taking zalcitabine. Stomatitis, esophageal ulceration, hepatotoxicity, rash, and pancreatitis may occur. Zalcitabine should be used with caution in individuals with a history of pancreatitis, liver disease, or alcohol abuse. Dosage adjustment is necessary for individuals with renal impairment. Zalcitabine should not be used in combination with didanosine, lamivudine, or stavudine. 

Didanosine (ddl) NRTT1 Tablets, 400 mg daily,3 adjusted for weight. 30 min before or 2 h after meals. Separate dosing from fluoroquinolones and tetracyclines by 2 h Peripheral neuropathy, pancreatitis, diarrhea, nausea, hyperuricemia. Possible increase in myocardial infarction Avoid concurrent neuropathic drugs (eg, stavudine, zalcitabine, isoniazid), ribavirin, and alcohol. Do not administer with tenofovir... 

Zalcitabine NRTI1 0.75 mg tid3 Administer 1 h before or 2 h after an antacid Peripheral neuropathy oral ulcerations, pancreatitis, headache, nausea, rash, arthralgias Avoid concurrent cimetidine avoid concurrent neuropathic drugs (eg, ddl, zalcitabine, isoniazid). Do not administer with lamivudine... 

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. 

Pancreatitis has been observed in patients treated with didanosine, lamivudine, stavudine, and zalcitabine (29), but its incidence is also increased in drug-naive patients with advanced HIV infection (30). 

Zalcitabine toxicides are similar to those of the other dideoxynucleoside analogs didanosine and stavudine. Severe peripheral neuropathy has been reported in up to 15% of patients. Peripheral neuropathy is dose related and more common with preexisting HIV-associated neuropathy and advanced HIV disease. This is a symmetrical dislal sensory neuropathy that begins in the feet but may progress to a stock-ing/glove distribution. Other specific risk factors for neuropathy include alcohol consumption, diabetes, and low vitamin Bi2 concentrations. If the dmg is stopped as soon as symptoms appear, the neuropathy usually stabilizes and should improve or resolve. Pancreatitis occurs rarely with zalcitabine therapy and appears to be less frequent than with didanosine. 

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. 

Of the NRTIs, didanosine, stavudine and zalcitabine have been associated with fatal pancreatitis. " ... 

The manufacturers of zalcitabine recommended that if a drug that has the potential to cause pancreatitis is required, treatment with zalcitabine should be interrupted. They specifically applied this to the use of pentamidine to treat Pneumocystis pneumonia. - ... 

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