Pentamidine 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. 

The manufacturers of didanosine have a similar recommendation and state that, if concurrent use is unavoidable, there should be close observation. Similarly, other authors recommend temporarily discontinuing didanosine in patients needing systemic pentamidine or sulfonamide-containing regimens. The UK manufacturer of stavudine recommends that patients receiving concurrent treatment with drugs known to cause pancreatitis should be carefully observed, and the US manufacturer specifically recommends caution with combined use of didanosine and stavudine, see NRTIs + NRTIs , p.800. Note that hydroxycarbamide (hydroxyurea) may increase the risk of pancreatitis with didanosine and stavudine, and the combination should probably be avoided, see NRTIs + Hydroxycarbamide , p.799. 

Episodes of acute pancreatitis and of hemorrhagic pancreatitis have been reported. This may or may not be combined with evidence of damage to pancreatic beta cells (SEDA-13, 825) (SEDA-16, 315) (SEDA-17, 331) (4). However, pancreatitis has also been seen in patients with AIDS who did not receive pentamidine. The risk of pancreatitis seems to be greater in children with CD4 counts under 100 x 10 /1. In a case-control study 12 of 44 patients with AIDS and pancreatitis had used pentamidine (SEDA-20, 264). 

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. 

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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