Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Physicians and researchers received a stronger warning from Bristol-Myers Squibb (BMS) this week about the risk of pancreatitis in patients taking ddI (Videx). The risk is higher if they are also taking d4T, with or without Hydroxyurea (Hydrea). There have been four deaths in recent clinical trials. Each of the four had CD4 counts greater than 500, viral loads below 200 copies, and were taking d4T. Two of the four were also enrolled in a study which included ddI, d4T, and Hydroxyurea, and three had known risk factors for pancreatitis. The new warning follows an October 27 letter from the FDA to BMS after an investigation found the drug company failed to disclose important safety information, and was promoting hydroxyurea for unapproved uses. The text of the warning letter, as well as a web site address for the full text of the FDA warning, is included.
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PMID:ddI, d4T, Hydroxyurea: new pancreatitis warning. 1136 25

Data from basic science and clinical studies suggest that hydroxyurea (hydroxycarbamide)-based regimens are effective treatment options for patients with HIV at various stages of disease. In vitro studies of HIV-infected lymphocytes have shown that hydroxyurea: (i) inhibits viral DNA synthesis; (ii) synergistically interacts with nucleoside reverse transcriptase inhibitors (NRTI); and (iii) increases the antiviral activity of didanosine. Clinical studies have confirmed that hydroxyurea in combination with didanosine produces potent and sustained viral suppression in patients with HIV infection. However, some concerns have been recently raised on the use of hydroxyurea in association with NRTI. Hydroxyurea can cause myelosuppression, skin toxicities, mild gastrointestinal toxicity, and abnormalities of renal and liver functions. In addition, hydroxyurea may accentuate the toxic effects of nucleoside analogues. In fact, some clinical data seem to indicate an increased risk of pancreatitis and neuropathy when hydroxyurea is combined with didanosine and stavudine. Since hydroxyurea-related toxicity is dose dependent, a systematic study of hydroxyurea optimal dosage and schedule was initiated to monitor patients for possible nucleoside toxicity. In the Research Institute for Genetic and Human Therapy (RIGHT) 702 study it was shown that a low, well-tolerated hydroxyurea dose (600 mg daily) achieved better antiretroviral activity than higher doses, together with better CD4+ cell count increase and fewer adverse effects. In this paper the effects of hydroxyurea as salvage therapy for heavily pretreated patients with advanced HIV disease are presented. These studies have shown that some patients with extensive pretreatment experience and advanced disease can respond substantially to the addition of hydroxyurea. The addition of hydroxyurea to didanosine does not prevent the emergence of resistance to didanosine; nonetheless, the efficacy of this therapeutic regimen may not be attenuated by the presence of didanosine-resistant HIV mutants. Since CD4 T lymphocyte activation is essential for virus replication and CD8 T lymphocyte activation may contribute to pathogenesis, the combination of hydroxyurea with other drugs may lead to the inhibition of HIV, by blocking the 'cell activation-virus production-pathogenesis' cycle. Clinical data indicate that hydroxyurea may play a role in attenuation of viral rebound and immune reconstitution by decreasing CD4 T cell proliferation, as well as preventing the exhaustion of CD8 T cell populations that may result from excessive activation during HIV infection. While the combination of hydroxyurea with didanosine has provided hope, future studies including those that evaluate optimal dosing and long-term toxicity are needed to define the role for this agent in the treatment of HIV infection.
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PMID:Hydroxyurea in the treatment of HIV infection: clinical efficacy and safety concerns. 1281 30