Probenecid, adverse drug reaction

The primary adverse effect of intravenous cidofovir is a dose-dependent nephrotoxicity. Concurrent administration of other potentially nephrotoxic agents (eg, amphotericin B, aminoglycosides, nonsteroidal anti-inflammatory drugs, pentamidine, foscarnet) should be avoided. Prior administration of foscarnet may increase the risk of nephrotoxicity. Other potential side effects include uveitis, decreased intraocular pressure, and probenecid-related hypersensitivity reactions. Neutropenia and metabolic acidosis are rare. The drug caused mammary adenocarcinomas in rats and is embryotoxic. 

Adverse reactions associated with probenecid therapy include occasional rashes, allergic dermatitis, upper gastrointestinal tract irritation, and drowsiness. The drug is contraindicated in patients with a history of renal calculi. 

However, there is also evidence that adverse reactions may be more common when this combination is used. During a pharmacokinetic study in healthy volunteers a 68-year-old woman developed severe thrombocytopenia after taking the combination, and no other drug therapy, for 2 weeks [266 j. Her platelet count fell from 200 to 15 X 10 /1. The two drugs were discontinued and her platelet count returned to normal within 1 week. In a review of the FDA s Adverse Event Reporting System database there were 93 cases of reduced platelet counts associated with oseltamivir and 24 associated with probenecid. Signal detection analyses were significant for oseltamivir but not probenecid. 

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