cidofovir
Vistide

Available forms
Available by prescription only
Injection: 75 mg/ml

Indications and dosages
 Cytomegalovirus (CMV) retinitis in patients with AIDS, acyclovir-resistant herpes simplex infections in immunocompromised patients ◇. Adults: 5 mg/kg I.V. infused over 1 hour once weekly for 2 consecutive weeks followed by maintenance dosage of 5 mg/kg I.V. infused over 1 hour once q 2 weeks. Probenecid must be administered concomitantly.
≡ Dosage adjustment. Reduce maintenance dosage to 3 mg/kg if serum creatinine level increases 0.3 to 0.4 mg/dl above baseline. Discontinue if serum creatinine level is more than 0.5 mg/dl above baseline or if 3+ or more proteinuria develops.

Pharmacodynamics
Antiviral action: Drug suppresses CMV replication by selective inhibition of viral DNA synthesis.

Pharmacokinetics
Absorption: Administered I.V.
Distribution: Unknown.
Metabolism: Not metabolized.
Excretion: 80% to 100% excreted unchanged in urine.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug and in those with a history of clinically severe hypersensitivity to probenecid or other sulfa drugs. Don’t administer as a direct intraocular injection, which may significantly decrease intraocular pressure and impair vision. Contraindicated in patients receiving nephrotoxic agents. Also contraindicated in patients with serum creatinine level of more than 1.5 mg/dl, a calculated creatinine clearance of 55 ml/minute or less, or a urine protein level of 100 mg/dl or more (equivalent to 2+ or more proteinuria). Use cautiously in patients with impaired renal function.

Interactions
Drug-drug. Ganciclovir ocular implants: May cause profound hypotony. Don’t give cidofovir within 1 month of placement of implant.
Nephrotoxic drugs (aminoglycosides, amphotericin B, foscarnet, I.V. pentamidine): May increase nephrotoxicity. Avoid use together.

Adverse reactions
CNS: malaise, asthenia, headache, amnesia, anxiety, confusion, seizures, abnormal gait, hallucinations, neuropathy, syncope, paresthesia, vasodilation, fever.
CV: orthostatic hypotension, pallor, tachycardia.
EENT: amblyopia, conjunctivitis, ocular hypotony, iritis, retinal detachment, uveitis, abnormal vision, rhinitis, sinusitis.
GI: nausea, vomiting, diarrhea, anorexia, abdominal pain, dry mouth, colitis, constipation, tongue discoloration, dyspepsia, dysphagia, flatulence, gastritis, melena, oral candidiasis, rectal disorders, stomatitis, aphthous stomatitis, mouth ulceration, taste perversion.
GU: nephrotoxicity, proteinuria, glycosuria, hematuria, urinary incontinence, urinary tract infection.
Hepatic: hepatomegaly.
Metabolic: fluid imbalances, hyperglycemia, hyperlipemia, hypocalcemia, hypokalemia, weight loss.
Musculoskeletal: myasthenia; pain in back, chest, or neck.
Respiratory: asthma, bronchitis, coughing, dyspnea, hiccups, increased sputum, lung disorders, pneumonia.
Skin: rash, alopecia, acne, skin discoloration, dry skin, pruritus, sweating, urticaria.
Other: infections, chills, allergic reactions, facial edema, sarcoma, herpes simplex, sepsis.

Effects on lab test results
• May increase BUN, creatinine, alkaline phosphatase, ALT, AST, and LDH levels. May decrease creatinine clearance levels.
• May decrease hemoglobin and neutrophil and platelet counts.

Overdose and treatment
No information available. However, hemodialysis and hydration may reduce drug levels in patients who receive an overdose. Probenecid may reduce the risk of nephrotoxicity in patients who receive an overdose through reduction of active tubular secretion.

Special considerations
• Don’t start drug if patient has baseline serum creatinine exceeding 1.5 mg/dl or calculated creatinine clearances of 55 ml/minute or less unless potential benefits exceed risks.
• Renal impairment is the major toxicity. To minimize the risk, use I.V. prehydration with normal saline solution and give probenecid with each cidofovir infusion.
• Give 1 liter of normal saline solution over a 1- to 2-hour period immediately before each cidofovir infusion. Give a second liter if patient can tolerate the additional fluid load. If the second liter is given, administer it either at the start of the cidofovir infusion or immediately afterward; infuse it over a 1- to 3-hour period.
• Give 2 g of probenecid P.O. 3 hours before cidofovir and 1 g at 2 hours, and again at 8 hours after completing the 1-hour infusion (total 4 g).
• To prepare infusion, extract the appropriate amount of cidofovir from the vial with a syringe and transfer the dose to an infusion bag containing 100 ml normal saline solution. Infuse entire volume I.V. at a constant rate over 1 hour. Use a standard infusion pump.
• Because of drug’s mutagenic properties, prepare it in a class II laminar flow biological safety cabinet. Wear surgical gloves and a closed front surgical-type gown with knit cuffs.
• If drug contacts the skin, wash and flush thoroughly with water. Place excess drug and all other materials used in admixture preparation and administration in a leak-proof, puncture-proof container. The recommended method of disposal is high-temperature incineration.
• Give cidofovir infusion admixtures within 24 hours of preparation; don’t refrigerate or freeze to extend this 24-hour period. If admixtures aren’t to be used immediately, they may be refrigerated at 36° to 46° F (2° to 8° C) for no longer than 24 hours. Allow refrigerated admixtures to reach room temperature before use.
• No other drugs and supplements should be added to the cidofovir admixture for concurrent administration. Compatibility with Ringer’s solution, lactated Ringer’s solution, and bacteriostatic infusion fluids hasn’t been evaluated.
• Safety and efficacy of cidofovir haven’t been established for other CMV infections, congenital or neonatal CMV disease, and CMV disease in patients not infected with HIV.
• Fanconi’s syndrome and decreased serum bicarbonate levels with evidence of renal tubular damage have been reported in patients receiving cidofovir. Monitor patient closely.
• Discontinue zidovudine therapy or reduce dosage by 50% in patients receiving zidovudine on the days cidofovir is given because probenecid reduces metabolic clearance of zidovudine.
• Monitor WBC counts with differential before each dose.
• Monitor renal function before each dose, and modify the dosage for changes in renal function.
• Granulocytopenia has been observed with cidofovir treatment; monitor neutrophil counts during therapy.
• Monitor intraocular pressure, visual acuity, and ocular symptoms periodically.
Pregnant patients
• Instruct women of childbearing potential to use contraception during and for 1 month after treatment with cidofovir.
• Tell men to use barrier contraceptives during and for 3 months after drug treatment.
Breast-feeding patients
• It isn’t known if drug appears in breast milk. Drug shouldn’t be given to breast-feeding women.
Pediatric patients
• Safety and effectiveness in children haven’t been established.
Geriatric patients
• Use cautiously when administering cidofovir to geriatric patients. Dosage adjustment will be necessary if patient is renally impaired.

Patient education
• Inform patient that drug isn’t a cure for CMV retinitis and that regular ophthalmologic follow-up is needed.
• Alert patients on zidovudine therapy that they’ll need to obtain dosage guidelines on days that cidofovir is administered.
• Tell patient that close monitoring of renal function will be needed during cidofovir therapy and that an abnormality may require a change in cidofovir therapy.
• Stress importance of completing a full course of probenecid with each cidofovir dose. Tell patient to take probenecid after a meal to decrease nausea.
• Advise patient that cidofovir is a carcinogen.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use