No

Antiviral Agent

Treatment of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS). Note: Should be administered with probenecid.

C

Clinical effect on the fetus: Although studies are inconclusive, adenocarcinomas have occurred in animal studies with cidofovir; use during pregnancy only if the potential benefit justifies the potential risk to the fetus

Breast-feeding/lactation: Excretion of cidofovir into breast milk is unknown

Patients with hypersensitivity to cidofovir and in patients with a history of clinically severe hypersensitivity to probenecid or other sulfa-containing medications

Dose-dependent nephrotoxicity requires dose adjustment or discontinuation if changes in renal function occur during therapy (eg, proteinuria, glycosuria, decreased serum phosphate, uric acid or bicarbonate, and elevated creatinine); avoid use in patients with creatinine >1.5 mg/dL; Cl_cr <55 mL/minute; use great caution with elderly patients; neutropenia and ocular hypotony have also occurred; safety and efficacy have not been established in children; administration must be accompanied by oral probenecid and intravenous saline prehydration; prepare admixtures in a class two laminar flow hood, wearing protective gear; dispose of cidofovir as directed

>10%:

Central nervous system: Infection, chills, fever, headache, amnesia, anxiety, confusion, seizures, insomnia

Dermatologic: Alopecia, rash, acne, skin discoloration

Gastrointestinal: Nausea, vomiting, diarrhea, anorexia, abdominal pain, constipation, dyspepsia, gastritis

Hematologic: Thrombocytopenia, neutropenia, anemia

Neuromuscular & skeletal: Weakness, paresthesia

Ocular: Amblyopia, conjunctivitis, ocular hypotony

Renal: Tubular damage, proteinuria, elevated creatinine

Respiratory: Asthma, bronchitis, coughing, dyspnea, pharyngitis

1% to 10%:

Cardiovascular: Hypotension, pallor, syncope, tachycardia

Central nervous system: Dizziness, hallucinations, depression, somnolence, malaise

Dermatologic: Pruritus, urticaria

Endocrine & metabolic: Hyperglycemia, hyperlipidemia, hypocalcemia, hypokalemia, dehydration

Gastrointestinal: Abnormal taste, stomatitis

Genitourinary: Glycosuria, urinary incontinence, urinary tract infections

Neuromuscular & skeletal: Skeletal pain

Ocular: Retinal detachment, iritis, uveitis, abnormal vision

Renal: Hematuria

Respiratory: Pneumonia, rhinitis, sinusitis

Miscellaneous: Diaphoresis, allergic reactions

No reports of acute toxicity have been reported, however, hemodialysis and hydration may reduce drug plasma concentrations; probenecid may assist in decreasing active tubular secretion

Increased effect/toxicity: Drugs with nephrotoxic potential (eg, amphotericin B, aminoglycosides, foscarnet, and I.V. pentamidine) should be avoided during cidofovir therapy

Store admixtures under refrigeration for less than or equal to 24 hours

Cidofovir is converted to cidofovir diphosphate which is the active intracellular metabolite; cidofovir diphosphate suppresses CMV replication by selective inhibition of viral DNA synthesis. Incorporation of cidofovir into growing viral DNA chain results in reductions in the rate of viral DNA synthesis.

The following pharmacokinetic data is based on a combination of cidofovir administered with probenecid:

Protein binding: <6%

Metabolism: Minimal; phosphorylation occurs intracellularly

Half-life, plasma: ~2.6 hours

Elimination: Renal tubular secretion and glomerular filtration

Induction: 5 mg/kg I.V. over 1 hour once weekly for 2 consecutive weeks

Maintenance: 5 mg/kg over 1 hour once every other week

Administer with probenecid - 2 g orally 3 hours prior to each cidofovir dose and 1 g at 2 and 8 hours after completion of the infusion (total: 4 g)

Hydrate with 1 L of 0.9% NS I.V. prior to cidofovir infusion; a second liter may be administered over a 1- to 3-hour period immediately following infusion, if tolerated

Dosing adjustment in renal impairment:

Cl_cr 41-55 mL/minute: 2 mg/kg

Cl_cr 30-40 mL/minute: 1.5 mg/kg

Cl_cr 20-29 mL/minute: 1 mg/kg

Cl_cr <19 mL/minute: 0.5 mg/kg

If the creatinine increases by 0.3-0.4 mg/dL, reduce the cidofovir dose to 3 mg/kg; discontinue therapy for increases greater than or equal to 0.5 mg/dL or development of greater than or equal to 3+ proteinuria

Renal function (Cr, BUN, UAs), LFTs, WBCs, intraocular pressure and visual acuity

Anxiety, confusion, amnesia, and insomnia are common; may cause depression or hallucinations

Anemia and neutropenia are common; use caution with clozapine and carbamazepine

No information available to require special precautions

No effects or complications reported

This drug can only be administered I.V. You may experience hair loss (reversible). You may be more susceptible to infection; avoid crowds and infectious situations. You may experience headache, anxiety, confusion; use caution when driving or engaging in tasks that require alertness until response to drug is known. You may experience GI upset (buttermilk or yogurt may help relieve diarrhea); frequent small meals, frequent mouth care, sucking lozenges, or chewing gum may relieve nausea, heartburn, or vomiting; and increased exercise and increased dietary fruit, fluids, or fiber may reduce constipation. You may experience postural hypotension; use caution changing from lying to sitting or standing position and when climbing stairs. Report severe unresolved vomiting, constipation or diarrhea, chills, fever, signs of infection, difficulty breathing or coughing, palpitations, chest pain, syncope, CNS changes (eg, hallucinations, depression, excessive sedation, amnesia, seizures, insomnia), or other severe side effects. Pregnancy/breast-feeding precautions: Inform prescriber if you are or intend to be sexually active or pregnant. Do not breast-feed.

Administration of probenecid with a meal may decrease associated nausea; acetaminophen and antihistamines may ameliorate hypersensitivity reactions; dilute in 100 mL 0.9% saline; administer probenecid and I.V. saline before each infusion; allow the admixture to come to room temperature before administration

Injection: 75 mg/mL (5 mL)

Akler ME, Johnson DW, Burman WJ, et al, "Anterior Uveitis and Hypotony After Intravenous Cidofovir for the Treatment of Cytomegalovirus Retinitis," Ophthalmology, 1998, 105(4):651-7.

Alrabiah FA and Sacks SL, "New Antiherpesvirus Agents. Their Targets

Garcia CR, Torriani FJ, and Freeman WR, "Cidofovir in the Treatment of Cytomegalovirus (CMV) Retinitis," Ocul Immunol Inflamm, 1998, 6(3):195-203.

Hitchcock MJ, Jaffe HS, Martin JC, et al, "Cidofovir, a New Agent With Potent Antiherpesvirus Activity," Antiviral Chem Chemother, 1996, 7:115-27.

Lalezari JP, Holland GN, Kramer F, et al, "Randomized, Controlled Study of the Safety and Efficacy of Intravenous Cidofovir for the Treatment of Relapsing Cytomegalovirus Retinitis in Patients With AIDS," J Acquir Immune Defic Syndr Hum Retrovirol, 1998, 17(4):339-44.

Lea AP and Bryson HM, "Cidofovir," Drugs, 1996, 52(2):225-30.

Taskintuna I, Rahhal FM, Capparelli EV, et al, "Intravitreal and Plasma Cidofovir Concentrations After Intravitreal and Intravenous Administration in AIDS Patients With Cytomegalovirus Retinitis," J Ocul Pharmacol Ther, 1998, 14(2):147-51.

Whitley RJ, Jacobson MA, Friedberg DN, et al, "Guidelines for the Treatment of Cytomegalovirus Diseases in Patients With AIDS in the Era of Potent Antiretroviral Therapy: Recommendations of an International Panel. International AIDS Society-USA," Arch Intern Med, 1998, 158(9):957-69.