Cidofovir

Pronunciation: (sigh-DAH-fah-vihr)
Class: Antiviral agent

Trade Names

Vistide
- Injection 75 mg/mL

Pharmacology

Inhibits viral DNA synthesis by interfering with viral DNA polymerase.

Pharmacokinetics

Absorption

Based on administration with probenecid, C _max is about 9.8 to 19.6 mcg/mL and AUC is about 25.7 to 40.8 mcg•h/mL.

Distribution

Vd is about 410 mL/kg (at steady state). Less than 6% protein bound.

Elimination

Cl is about 148 mL/min/1.73 m ² . Renal Cl is about 98.6 mL/min/1.73 m ² .

Special Populations

Renal Function Impairment

Cl decreases proportionally with Ccr. Dosage adjustment is recommended.

Indications and Usage

Treatment of CMV retinitis in patients with AIDS.

Contraindications

History of clinically severe hypersensitivity to probenecid or other sulfa-containing medications; direct intraocular injection. Patients receiving agents with a nephrotoxic potential must discontinue use of such agents at least 1 wk prior to beginning therapy. Initiation of therapy in patients with a serum creatinine greater than 1.5 mg/dL, a calculated Ccr of less than or equal to 55 mL/min, or a urine protein at least 100 mg/dL.

Dosage and Administration

Adult Induction

IV 5 mg/kg once weekly for 2 consecutive weeks.

Maintenance dose

IV 5 mg/kg once every 2 wk.

Nephrotoxicity

Reduce the dose of cidofovir to 3 mg/kg for increases in serum creatinine (0.3 to 0.4 mg/dL).

Probenecid

Administer probenecid orally with each dose of cidofovir. Probenecid 2 g given 3 h prior to the cidofovir dose and 1 g administered 2 h and again at 8 h after completion of the cidofovir infusion.

General Advice

• For IV infusion only. Do not administer by direct intraocular injection.
• Follow National Institutes of Health guidelines for handling and disposal of this mutagenic agent.
• Inspect vial for particulate matter and discoloration. Do not use if noted.
• Prescribed dose must be withdrawn from vial and diluted in 100 mL of isotonic sodium chloride solution before IV administration.
• Administer diluted solution over 1 h using infusion pump.
• Patient should receive 1 L of normal saline infused over a 1- to 2-h period immediately before the cidofovir infusion.
• Administer a second liter of normal saline at the start of the cidofovir infusion or immediately afterward if the patient can tolerate it, and infuse over 1 to 3 h.
• Discard any unused medication remaining in vial.

Storage/Stability

• Unopened vial can be stored at room temperature (68° to 77°F).
• IV admixtures may be stored for 24 h under refrigeration (36° to 46°F).
• Warm IV solution to room temperature before administration.

Drug Interactions

Nephrotoxic agents (eg, aminoglycosides, amphotericin B, foscarnet, IV pentamidine)

Risk of nephrotoxicity is increased.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypotension; postural hypotension; pallor; syncope; tachycardia.

CNS

Headache; amnesia; anxiety; confusion; convulsion; depression; dizziness; abnormal gait; hallucinations; insomnia; neuropathy; paresthesia; somnolence; vasodilation.

Dermatologic

Alopecia; rash; acne; skin discoloration; dry skin; herpes simplex; pruritus; sweating; urticaria.

EENT

Amblyopia; conjunctivitis; eye disorder; iritis; retinal detachment; uveitis; abnormal vision; hypotonia.

GI

Nausea; vomiting; diarrhea; anorexia; abdominal pain; colitis; constipation; tongue discoloration; dyspepsia; dysphagia; flatulence; gastritis; melena; oral candidiasis; rectal disorder; stomatitis; aphthous stomatitis; mouth ulceration; dry mouth; taste perversion.

Genitourinary

Renal toxicity; proteinuria; elevated creatinine and decreased Ccr; glycosuria; hematuria; urinary incontinence; UTI.

Hematologic

Thrombocytopenia; neutropenia; anemia.

Hepatic

Hepatomegaly; abnormal LFTs; increased AST; increased ALT.

Metabolic

Dehydration; hyperglycemia; hyperlipidemia; hypocalcemia; hypokalemia; metabolic acidosis; increased alkaline phosphatase; weight loss.

Respiratory

Asthma; bronchitis; coughing; dyspnea; hiccough; increased sputum; lung disorder; pharyngitis; pneumonia; rhinitis; sinusitis.

Miscellaneous

Allergy; edema; malaise; back pain; chest pain; neck pain; sarcoma; sepsis; arthralgia; asthenia; myasthenia; myalgia; fever; chills; infection.

Precautions

Warnings Animal data Carcinogenic and teratogenic effects and impaired fertility reported. Nephrotoxicity Major toxicity occurs. Cases of acute renal failure resulting in dialysis and/or contributing to death occurred with as few as 1 or 2 doses. Reduce possible nephrotoxicity with IV prehydration (normal saline) and administration of probenecid. Monitor serum creatinine and urine protein within 48 h prior to each dose. Dose adjustment required for changes in renal function. Neutropenia May occur; monitor neutrophil count.

Monitor Creatine/Urine protein/WBC Monitor serum creatinine, urine protein, and WBC with differential prior to each dose. If proteinuria is noted, administer IV hydration and repeat the test. Ocular symptoms Ensure that IOP, visual acuity, and ocular symptoms are periodically monitored.

Pregnancy

Category C .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Elderly

Because elderly individuals frequently have reduced glomerular filtration, assess renal function before and during cidofovir therapy.

Renal Function

Cidofovir administration is not recommended if serum creatinine greater than 1.5 mg/dL or Ccr less than or equal to 55 mL/min.

Contraception

Women of childbearing potential should use effective contraception during and for 1 mo following treatment. Men should use a barrier contraceptive during and for 3 mo following treatment.

Intraocular pressure

May be associated with decreases in intraocular pressure and impairment of vision.

Direct intraocular injection

May be associated with iritis, ocular hypotony, and permanent impairment of vision.

Metabolic acidosis

Decreased serum bicarbonate associated with proximal tubule injury and renal wasting syndrome may occur.

Uveitis/Iritis

Uveitis/Iritis has been reported.

Zidovudine

If patient is taking zidovudine, ensure that zidovudine is discontinued or reduce dose by 50% on days of cidofovir infusion.

Patient Information

• Advise patient that this medication does not cure CMV retinitis and that progression of retinitis during and following treatment may be experienced.
• Instruct patient to continue taking the antiretroviral therapy. However, if patient is taking zidovudine, to either reduce the dose by ½ or stop on days of cidofovir administration.
• Instruct patient taking oral cidofovir that it is essential to take a full course of probenecid with each dose (2 g 3 h before and 1 g 2 h and 8 h after completing the infusion).
• Inform patient that taking the probenecid after a meal or the use of antiemetics may decrease nausea.
• Instruct patient of childbearing potential that cidofovir is embryotoxic and that appropriate contraceptive methods should be used by women during treatment and for 1 mo after treatment is completed. Men should use barrier contraceptive during and for 3 mo following completion of therapy.
• Advise patient that regular eye examinations will be necessary and to keep appointments.
• Advise patient to report any suspected adverse reactions to health care provider.
• Inform patient of the major toxicities of cidofovir, ie, renal function impairment, and that dose modification, including reduction, interruption, and discontinuation may be necessary.
• Advise patient that cidofovir causes tumors (eg, mammary adenocarcinomas) in rats and should be considered a potential carcinogen in humans.

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