Nephrotoxicity is the principal dose-limiting side effect of intravenous cidofovir. Proximal tubular dysfunction includes proteinuria, azotemia, glycosuria, and metabolic acidosis. Concomitant oral probenecid and saline prehydration reduce the risk of renal toxicity. On maintenance doses of 5 mg2kg every 2 weeks, up to 50% of patients develop proteinuria, 10—15% show an elevated serum creatinine, and 15—20% develop neutropenia. Anterior uveitis that is responsive to topical glucocorticoids and cycloplegia occur commonly and ocular hypotony occurs infrequently with intravenous cidofovir. Administration with food and pretreatment with antiemetics, antihistamines, and2or acetaminophen may improve tolerance.
Probenecid but not cidofovir alters zidovudine pharmacokinetics such that zidovudine doses should be reduced when probenecid is present, as should the doses of drugs similarly affected by probenecid (e.g., ^-lactam antibiotics, nonsteroidal anti-inflammatory drugs [NSAIDs], acyclovir, lorazepam, furosemide, methotrexate, theophylline, and rifampin). Concurrent nephrotoxic agents are contraindicated, and an interval of 1 week before beginning cidofovir treatment is recommended after prior exposure to aminoglycosides, intravenous pentamidine, amphotericin B, foscarnet, NSAIDs, or contrast dye. Cidofovir and oral ganciclovir in combination are poorly tolerated at full doses.
Topical application of cidofovir is associated with local reactions (e.g., burning, pain, and pruritus) in up to one-third of patients and occasionally ulceration.
Cidofovir is considered a potential human carcinogen and is classified as pregnancy category C.
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