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Therapeutic Classification: antivirals

• Management of cytomegalovirus (CMV) retinitis in HIV-infected patients (with probenecid).

• Suppresses replication of CMV by inhibiting viral DNA synthesis.

• Slows progression of CMV retinitis; may not be curative.

Absorption: IV administration results in complete bioavailability.

Distribution: Unknown.

Metabolism/Excretion: Excreted mostly unchanged by the kidneys.

Half-life: Unknown.

Contraindicated in:

• Hypersensitivity to cidofovir, probenecid, or sulfonamides
• Serum Cr >1.5 mg/dL, CCr 55 mL/min, or urine protein 100 mg/dL (2+ proteinuria)
• Concurrent use of foscarnet, amphotericin B, aminoglycoside anti-infectives, NSAIDs, or IV pentamidine.

Use Cautiously in:

• OB: Pedi: Safety not established
• Lactation: Breastfeeding is not recommended in HIV-positive patients

Exercise Extreme Caution in:

• Any condition or medication that ↑ the risk of dehydration.

Derm: alopecia, rash.

EENT: ↓intraocular pressure, hearing loss, iritis, ocular hypotony, uveitis.

F and E: ↓serum bicarbonate.

GI: abdominal pain, nausea, vomiting, anorexia, diarrhea, HEPATOTOXICITY, PANCREATITIS.

GU: proteinuria, RENAL FAILURE.

Hemat: neutropenia, anemia.

Metab: METABOLIC ACIDOSIS.

Neuro: headache, weakness.

Resp: dyspnea, pneumonia.
Misc: chills, fever, infection.

Drug-Drug:

• ↑risk of nephrotoxicity with aminoglycosides, amphotericin B, foscarnet, and pentamidine and should be avoided; wait 7 days after giving other nephrotoxic agents.
• Probenecid, which is required concurrently, may interact with acetaminophen, acyclovir, ACE inhibitors, barbiturates, benzodiazepines, bumetanide, methotrexate, famotidine, furosemide, NSAIDs, theophylline, and zidovudine.

• IV (Adults): 5 mg/kg once weekly for 2 wk, followed by 5 mg/kg every 2 wk (must be given with probenecid).

(Generic available)

• Solution for injection: 75 mg/mL;

• Monitor vision for progression of CMV retinitis. Monitor ocular symptoms, intraocular pressure, and visual acuity periodically.
• Antiemetics and administration after a meal may minimize nausea and vomiting associated with probenecid. If allergic reactions occur in association with probenecid, pretreatment with antihistamines or acetaminophen should be considered.
• Monitor vital signs periodically. May cause fever, hypotension, and tachycardia. Monitor patients for early signs and symptoms of infection.

• Renal function, measured by serum Cr and urine protein, must be monitored within 48 hr before each dose and throughout cidofovir therapy. In patients with proteinuria, administer IV hydration and repeat urine protein test. If renal function deteriorates, dose modification or temporary discontinuation should be considered.
  • Monitor WBC before each dose. Granulocytopenia may occur.
  • May cause hyperglycemia, hyperlipemia, hypocalcemia, hypokalemia, and elevated alkaline phosphatase, AST, and ALT.

• Probenecid and saline prehydration must be given with cidofovir to minimize renal toxicity. Probenecid must be administered 2 g orally given 3 hr before, then 1 g given 2 hr and 8 hr after completion of cidofovir infusion. Saline prehydration with 1 L of 0.9% NaCl must be given over 1–2 hr before cidofovir. A second liter over 1–3 hr is recommended concurrently with or after cidofovir.
  • Patients receiving foscarnet, amphotericin B, aminoglycoside, NSAIDs, or IV pentamidine should wait at least 7 days after these agents to begin cidofovir.

IV Administration:

• Intermittent Infusion: Dilute in 100 mL of 0.9% NaCl. Solution is stable for 24 hr if refrigerated. Allow refrigerated solution to return to room temperature before administration.
• Rate: Administer over 1 hr.
• Additive Incompatibility: Information unavailable. Do not admix with other solutions or medications.

• Inform patient that cidofovir is not a cure for CMV retinitis and that retinitis may continue to progress during and after therapy.
• Inform patient that concurrent antiretroviral therapy may be continued. However, zidovudine therapy should be temporarily discontinued or decreased by 50% on the days of cidofovir therapy because of the effects of probenicid on zidovudine.
• Advise patient of the possibility of renal toxicity from cidofovir. Emphasize the importance of routine lab tests to monitor renal function.
• Discuss with patient the possibility of hair loss. Explore coping strategies.
• Advise patients to have routine ophthalmologic exams after cidofovir therapy.
• Inform patient that cidofovir may have teratogenic effects. Women should use contraception during and for 1 mo after therapy. Men should use barrier contraception during and for 3 mo after therapy.

• Decrease in symptoms and arrest of progression of CMV retinitis in HIV-infected patients.

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