Usual Adult Dose for CMV Retinitis

Dose, Frequency, and Infusion Rate Must Not Be Exceeded; Probenecid and IV Saline Prehydration Must Be Administered with Each Dose

Induction dose: 5 mg/kg via IV infusion once a week for 2 consecutive weeks
Maintenance dose: Following induction dose, 5 mg/kg via IV infusion once every 2 weeks

Comments:

• Probenecid dose: 2 g orally 3 hours prior to infusion, then 1 g orally at 2 and 8 hours following completion of infusion (total probenecid dose equals 4 g)
• IV infusion should be given at a constant rate over 1 hour; consult preparation and administration section for important instructions on preparing and administering infusion.
• Serum creatinine and urine protein must be checked within 48 hours of each dose; because serum creatinine may not provide a complete picture of underlying renal status in patients with advanced AIDS and CMV retinitis, it is important to utilize the Cockcroft-Gault formula to more precisely estimate CrCl.
• The safety and efficacy of this drug has not been established for the treatment of other CMV infections such as pneumonitis or gastroenteritis, congenital or neonatal CMV disease, or CMV disease in non-HIV-infected individuals.

Usual Adult Dose for Smallpox Vaccine Reaction

(Not approved by FDA)

5 mg/kg via IV infusion once

A second dose 1 week later may be considered if clinically indicated.

Cidofovir is available under an IND protocol from the CDC as a second-line treatment of severe smallpox vaccine complications that have not responded to vaccinia immune globulin (VIG) treatment.

Renal Dose Adjustments

Moderate to severe renal impairment (calculated CrCl 55 mL/min or less, serum creatinine greater than 1.5 mg/dL, or urine protein 100 mg/dL or greater [equivalent to 2+ proteinuria or greater]): Contraindicated

Changes in renal function during therapy:
For increase in serum creatinine of 0.3 to 0.4 mg/dL above baseline: Maintenance dose must be reduced to 3 mg/kg.
For increase in serum creatinine of 0.5 mg/dL or greater above baseline or development of 3+ proteinuria or greater: Therapy must be discontinued.

Liver Dose Adjustments

No adjustment recommended

Dose Adjustments

Elderly:

• Safety and effectiveness have not been studied in patients over the age of 60 years.
• Since elderly individuals frequently have reduced glomerular filtration, particular attention should be paid to assessing renal function before and during cidofovir administration.

• Tolerability may be improved by administering with food; antiemetic therapy may reduce potential for nausea.
• In patients who develop allergic or hypersensitivity symptoms, an appropriate prophylactic or therapeutic antihistamine and/or acetaminophen should be considered.

• Due to an interaction of zidovudine with probenecid, zidovudine dose should be held or decreased by 50% on days of cidofovir injection.

Precautions

US BOXED WARNINGS: NEPHROTOXICITY; NEUTROPENIA; CARCINOGENICITY, TERATOGENICITY; and HYPOSPERMIA:

• Renal impairment is the major toxicity of therapy. Cases of acute renal failure resulting in dialysis and/or contributing to death have occurred with as few as 1 or 2 doses. To reduce possible nephrotoxicity, IV prehydration with normal saline and administration of probenecid must be used with each dose. Renal function (serum creatinine and urine protein) must be monitored within 48 hours prior to each dose and the dose must be modified for changes in renal function. This drug is contraindicated in patients who are receiving other nephrotoxic agents.
• Neutropenia has been observed in association with this drug; therefore, neutrophil counts should be monitored during therapy.
• This drug is indicated only for the treatment of CMV retinitis in patients with Acquired Immunodeficiency Syndrome (AIDS).
• In animal studies, this drug was carcinogenic, teratogenic, and caused hypospermia.

Dialysis

Contraindicated

• High-flux hemodialysis reduces serum levels of cidofovir by about 75%.

Other Comments

Administration advice:

• For IV infusion only; dilute in 100 mL of normal saline prior to administration
• Administer as IV infusion at a constant rate over 1 hour; use of a standard infusion pump is recommended

• Begin course of probenecid 3 hours prior to infusion; administer orally with food to reduce drug-related nausea and vomiting
• Begin hydration with at least 1 L of normal saline 1 to 2 hours prior to infusion; patients who can tolerate additional fluid should receive a second liter either at the start of the cidofovir infusion or immediately following and infused over a 1 to 3-hour period

• Prepare infusion by extracting the appropriate volume of drug from vial and transferring to an infusion bag containing 100 mL normal saline.
• Due to mutagenic properties, use of appropriate safety equipment for preparation, administration, and disposal is recommended.

• Addition of other drugs or supplements is not recommended
• Compatibility with Ringer's solution, Lactated Ringer's solution or bacteriostatic infusion fluid has not been evaluated

• Chemical stability has been demonstrated in polyvinyl chloride and ethylene/propylene copolymer composition commercial infusion bags, and in glass bottles.
• Prepared admixtures should be used promptly, however, may store under refrigeration (2C to 8C) for up to 24 hours.

• Concomitant use with other drugs with potential nephrotoxicity is contraindicated; potentially nephrotoxic drugs should be stopped at least 7 days before this drug is initiated.
• Direct intraocular injection is contraindicated as it has been associated with iritis, ocular hypotony, and permanent vision impairment.
• As a full course of probenecid must be administered with each dose of this drug, it is important to consider potential drug interactions and potential adverse events associated with this drug; administering after a meal or with antiemetics may decrease the nausea and prophylactic or therapeutic antihistamines and/or acetaminophen can be used to lessen hypersensitivity reactions.

• Serum creatinine and urine protein must be checked within 48 hours of each dose; calculate CrCl using Cockcroft-Gault formula
• If proteinuria is present, start IV hydration and retest
• Monitor white blood counts with differential prior to each dose
• Intraocular pressure, visual acuity, and ocular symptoms should be monitored periodically

• Patients should understand the importance of completing a full course of probenecid with each dose of this drug, they should be warned of potential adverse effects of probenecid and what they may be able to do to minimize them.
• Patients should be advised that this drug has caused embryotoxic and impaired fertility in animals and these effects may occur in humans; contraceptive measures are advised for men and women of childbearing potential.

Frequently asked questions

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