Cidofovir

Cytomegaloviral retinitis in AIDS patients

Intravenous Cytomegaloviral retinitis in AIDS patients Adult: Induction: 5 mg/kg by infusion over 1 hr once wkly for 2 consecutive wk. Maintenance: 5 mg/kg once every 2 wk, starting 2 wk after completion of induction treatment.

Renal impairment CrCl >55 mL/min and urine protein <100 mg/dL (equivalent to <2+ proteinuria): No dosage adjustment required Serum creatinine increases 0.3-0.4 mg/dL above baseline: Reduce maintenance dose to 3 mg/kg Serum creatinine increases>0.5 mg/dL above baseline or ?3+ proteinuria: Discontinue Preexisting renal impairment Serum creatinine >1.5 mg/dL(creatinine clearance ?55 mL/min) or urine protein >100 mg/dL (equivalent to >2+ proteinuria): Contraindicated

Administer w/ oral probenecid 2 g, 3 hr prior to each cidofovir dose, further doses of 1 g at 2 and 8 hr after completion of infusion. Hydration: Infuse 1 L normal saline over 1-2 hr immediately before cidofovir infusion; if patient can tolerate additional water load, a 2nd liter may be given over 1-3 hr at the start of or immediately following infusion. IV Preparation Administer within 24 hr of dilution; refrigerate if not used immediately but still use within 24 hr Admixtures should be allowed to equilibrate to room temp prior to use IV Administration For IV infusion only Infuse in 100 mL NS over 1 hr Prehydrate with 1 L of NS IV over 1-2 hr prior to cidofovir infusion; a second liter may be administered over a 1-3 hr period immediately following infusion, if tolerated

Hypersensitivity to cidofovir and probenecid or other sulfur-containing medicines. Direct intraocular inj. Renal impairment (serum creatinine >1.5 mg/dL, CrCl <55 mL/min, or urine protein >100 mg/dL [>2+ proteinuria]). Lactation. Concomitant use or w/in 7 days of treatment w/ potentially nephrotoxic drugs.

Renal impairment is the major toxicity, and acute renal failure resulting in dialysis or contributing to death have occurred with as few as 1 or 2 doses Reduce nephrotoxicity risk by IV prehydration with normal saline, and administration of probenecid must be used with each infusion Renal function (serum creatinine and urine protein) must be monitored within 48 hr prior to each dose, and, if necessary, modify dose in renal function as appropriate Contraindicated if taking other nephrotoxic agents Neutropenia observed; monitor neutrophil counts Indicated only for the treatment of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS) Animal studies showed cidofovir was carcinogenic, teratogenic, and caused hypospermia Monitoring Parameters Monitor for renal function (serum creatinine and urine protein) w/in 48 hr prior each dose and WBC including neutrophil count prior to each dose; Regular eye examinations: signs/symptoms of uveitis/iritis, metabolic acidosis.

Not Classi Pregnancy No adequate and well-controlled studies to date in pregnant women; use during pregnancy only if potential benefits justify potential risks to fetus Inform women of childbearing potential that this drug is embryotoxic in animals Advise women of childbearing potential to use an effective method of contraception during and for 1 month after cidofovir therapy Advise men to use a reliable method of barrier contraception during and for 3 months after therapy Animal data In animals, this drug has caused reduced testes weight and hypospermia; possibility exists that such effects could occur in humans and cause infertility Lactation Not known whether distributed into human milk; either discontinue nursing or the drug. Instruct HIV-infected women not to breast-feed because of risk of HIV transmission

Increased risk of adverse inflammatory effects when administered w/ 2-4 wk of intravitreal fomivirsen. Potentially Fatal: Increased risk of nephrotoxicity w/ potentially nephrotoxic drugs (e.g. aminoglycosides, amphotericin B, foscarnet, IV pentamidine, vancomyicn, NSAIDs). Contraindicated (8) amikacin amphotericin B deoxycholate contrast media (iodinated) cyclosporine ioversol neomycin PO tacrolimus teicoplanin

>10% Infection Chills Fever Headache Amnesia Anxiety Confusion Seizures Insomnia Weakness Paresthesia Alopecia Rash Acne Skin discoloration Nausea Vomiting Diarrhea Anorexia Abdominal pain Constipation Dyspepsia Gastritis Thrombocytopenia Neutropenia Anemia Amblyopia Conjunctivitis Ocular hypotony Tubular damage Proteinuria Elevated creatinine 1-10% Hypotension Diaphoresis Pallor Syncope Tachycardia Dizziness Hallucinations Depression Somnolence Malaise Pruritus Urticaria Hyperglycemia Hyperlipidemia Hypocalcemia Hypokalemia Dehydration Abnormal taste Stomatitis Glycosuria Hematuria Urinary incontinence Urinary tract infections Skeletal pain Retinal detachment Iritis Uveitis Abnormal vision Pneumonia Rhinitis Sinusitis Allergic reactions

Cidofovir is a purine nucleotide analog that is active against herpesviruses and certain other viruses. It is converted to its active intracellular metabolite, cidovir diphosphate, and supresses CMV replication by selectively inhibiting viral DNA synthesis. Also, it reduces the rate of viral DNA synthesis by incorporation into growing viral DNA chains.