Nephrotoxicity cidofovir

OAT Penicillin Methotrexate Cidofovir Furosemide Various Probenecid NSAIDS Probenecid Probenecid Uremic Toxins f duration of action of penicillin f plasma exposure of methotrexate leading to toxicity J, kidney accumulation and lower incidence of cidofovir nephrotoxicity J, diuretic activity of furosemide J, excretion of OAT substrates... 

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. 

Because of its potential nephrotoxicity, cidofovir should not be used in individuals with renal impair-... 

Intravenous cidofovir is effective for the treatment of CMV retinitis and is used experimentally to treat adenovirus infections. Intravenous cidofovir must be administered with high-dose probenecid (2 g at 3 hours before the infusion and 1 g at 2 and 8 hours after), which blocks active tubular secretion and decreases nephrotoxicity. Cidofovir dosage must be adjusted for alterations in the calculated creatinine clearance or for the presence of urine protein before each infusion, and aggressive adjunctive hydration is required. Initiation of cidofovir therapy is contraindicated in patients with existing renal insufficiency. Direct intravitreal administration of cidofovir is not recommended because of ocular toxicity. 

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. 

Second, certain nucleotide phosphonates (e.g., adefovir and cidofovir) are effective antivirals, but their use in the clinic is limited by renal toxicity. This is believed to be caused by avid uptake at the basolateral membrane of renal proximal tubule cells followed by slow transport into the urine at the apical membrane, a sequence of events that results in intracellular drug accumulation and thus toxicity. As with penicillin, the OAT family of transporters has been implicated in cidofovir uptake. Co-administration of probenecid with cidofovir has been shown to decrease renal clearance of the antiviral and reduce its nephrotoxicity, presumably through com-... 

Increased nephrotoxicity with tenofovir, cidofovir, acyclovir, cyclosporine, gancyclovir... 

Increased risk of nephrotoxicity with cidofovir, aminoglycosides, carbopla-tin, cisplatin, clofarabine, efavirenz/emtricitabine/tenofovir, tacrolimus... 

Increased nephrotoxicity with cidofovir, aminoglycosides, carboplatin, cisplatin, clofarahine, efavirenz/emtricitahine/tenofovir, gallium, tenofovir... 

Cidofovir Intravenous administration Primary toxicity = nephrotoxicity... 

Ind avenous cidofovir is well tolerated. The major deatment-limidng toxicity of this drug is irreversible nephrotoxicity (Plosker and Noble, 1999). Ind avenous pre-hydradon with normal saline and aclminisdadon of oral probenecid must be used with each cidofovir infusion to lessen the effects on the kidney. Serum creadnine and urine protein must be monitored with each infusion and adjusted accordingly. Other adverse effects associated with its use are neudopenia and peripheral neuropathy (Plosker and Noble, 1999). 

During long-term follow-up of patients with AIDS treated with parenteral cidofovir for CMV retinitis, the median time to discontinuation for intolerance was 6.6 months (11). Cidofovir-associated uveitis occurred in 10 of 58 patients and ocular hypotony (a 50% fall in intraocular pressure from baseline to below 5 mmHg) occurred at a rate of 0.16 per person-year. There were 51 episodes of proteinuria in 30 of the 58 patients and 82% of these episodes resolved on withdrawal (median time to resolution 20 days). No nephrotoxic events required dialysis. 

Skiest DJ, Duong M, Park S, Wei L, Keiser P. Comphcations of therapy with intravenous cidofovir severe nephrotoxicity and anterior uveitis. Infect Dis Clin Pract 1999 83 151-7. 

Nephrotoxicity was found in preclinical studies to be the major toxicity of cidofovir, associated with histologic evidence of damage to proximal tubule epithelial cells [33]. Dose- and schedule-dependent nephrotoxicity is also the treatment limiting toxicity of cidofovir in humans [34-37]. Cidofovir is thought to be concentrated by a basolateral membrane or-... 

Cidofovir 5 mg/kg weekly X 2 (induction) 5 mg/kg every 2 wk 90% 100% No data avoid No data avoid Dose-limiting nephrotoxicity with proteinuria, glycosuria, renal insufficiency nephrotoxicity and renal clearance reduced with coadministration of probenecid No data avoid No data avoid No data avoid... 

OATl (SLC22A6) Probenecid Cidofovir Decrease renal CL by 27%, which is sufficient to reduce cidovovir nephrotoxicity Inhibition of renal proximal tubular basolateral OATl... 

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