Neutropenia cidofovir

WARNING Renal impair is the major tox foUow administration instructions Uses CMV retinitis w/ HIV Action Selective inhibition of viral DNA synth Dose Rx 5 mg/kg IV over 1 h once/wk for 2 wk w/ probenecid Maint 5 mg/kg IV once/2 wk w/ probenecid (2 g PO 3 h prior to cidofovir, then 1 g PO at 2 h 8 h after cidofovir) X in renal impair Caution [C, -] Contra Probenecid or sulfa allergy Disp Inj SE Renal tox, chills, fever, HA, NA /D, thrombocytopenia, neutropenia Interactions t Nephrotox W/ aminoglycosides, amphot icin B, foscar-net, IV pentamidine, NSAIDs, vancomycin t effects W/zidovudine EMS Monitor ECG for hypocalcemia (t QT int val) and hypokalemia (flattened T waves) OD May cause renal failure hydration may be effective in reducing drug levels/effects Cilostazol (Pletal) TAntiplatelet, Arterial Vasodilator/ Phosphodiesterase Inhibitor] Uses Reduce Sxs of intermittent claudication Action Phosphodiesterase in inhibitor t s cAMP in pits blood vessels, vasodilation inhibit pit aggregation Dose 100 mg PO bid, 1/2 h before or 2 h after breakfast dinner Caution [C, +/-] Contra CHE, hemostatic disorders. 

Anterior uveitis and neutropenia are fairly common side effects of cidofovir therapy. Ocular hypotony and metabolic acidosis are rare. Exposure to therapeutic levels of cidofovir causes cancer in rats therefore, this drug should be considered a potential human carcinogen. Animal studies have also shown cidofovir to produce embryotoxic and teratogenic effects and to impair fertility. 

Adverse Effects. Cidofovir may cause nephrotoxicity, especially at higher doses. This drug may also decrease the number of neutrophilic leukocytes, resulting in neutropenia and related symptoms such as fever, chills, and sore throat. Other side effects include headache and gastrointestinal disturbances (anorexia, nausea, diarrhea). 

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. 

Intravenous cidofovir is well tolerated. The major treatment-limiting toxicity of this drug is irreversible nephrotoxicity (Plosker and Noble, 1999). Intravenous pre-hydration with normal saline and administration of oral probenecid must be used with each cidofovir infusion to lessen the effects on the kidney. Serum creatinine and urine protein must be monitored with each infusion and adjusted accordingly. Other adverse effects associated with its use are neutropenia and peripheral neuropathy (Plosker and Noble, 1999). 

In a rare cytomegalovirus comparison trial, a ganciclovir insert (an intraocular implant) plus oral ganciclovir was compared with intravenous cidofovir (18). Based on data from 61 patients (the trial was stopped early owing to low recruitment), cidofovir was associated with a raised serum creatinine concentration of 142 pmol/l (1.6 mg/dl) or greater (0.48 per person-year), 3+ or greater proteinuria (0.29 per person-year), uveitis (0.35 per person-year), and neutropenia (0.11 per person-year). 

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 mg/kg every 2 weeks, up to 5Wo 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, and/or acetaminophen may improve tolerance. 

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