Cidofovir

(sigh-DAH-fah-vihr)

  Action:
Inhibits viral DNA synthesis by interfering with viral DNA polymerase.

  Indications:
Treatment of CMV retinitis in patients with acquired immunodeficiency syndrome (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 1 wk prior to beginning therapy. Initiation of therapy in patients with a serum creatinine > 1.5 mg/dL, a calculated Ccr of 55 mL/min, or a urine protein 100 mg/dL.

  Route/Dosage:

Adult: Induction:
IV 5 mg/kg once weekly for 2 consecutive weeks. Maintenance dose:
IV 5 mg/kg once q 2 wk.

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

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

  Interactions:

Nephrotoxic agents (eg, aminoglycosides, amphotericin B, foscarnet, IV pentamidine): Risk of nephrotoxicity is increased.

  Lab Test Interferences:
None well documented.

  Adverse Reactions:

CV:

Hypotension; postural hypotension; pallor; syncope; tachycardia.

CNS:

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

DERM:

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 pervision.

GU:

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

HEMA:

Thrombocytopenia; neutropenia; anemia.

HEPA:

Hepatomegaly; abnormal LFTs; increased AST; increased ALT.

META:

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

RESP:

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

OTHER:

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

  Precautions:

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.

Monitoring: Monitor serum creatinine, urine protein, and WBC with differential prior to each dose.

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.

Nephrotoxicity: Dose-related nephrotoxicity may occur. Dosage adjustment or discontinuation is required for changes in renal function. Cases of acute renal failure resulting in dialysis or contributing to death have occurred with as few as 1 or 2 doses.

Neutropenia: May occur; monitor neutrophil count.

Renal function impairment: Cidofovir administration is not recommended if serum creatinine > 1.5 mg/dL or Ccr 55 mL/min.

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 have been reported.

  Administration/Storage:

• For IV infusion only. Do not administer by direct intraocular injection.
• Follow NIH 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 Normal Saline before IV administration.
• Administer diluted solution over 1 hr using infusion pump.
• Patient should receive 1 L of Normal Saline infused over a 1- to 2-hr 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 hr.
• Unopened vial can be stored at room temperature (68° to 77°F).
• Discard any unused medication remaining in vial.
• IV admixtures may be stored for 24 hr under refrigeration (36° to 46°F).
• Warm IV solution to room temperature before administration.

  Assessment/Interventions:

• Obtain patient history, including drug history and any known allergies.
• Report any suspected side effects to health care provider.
• Ensure that serum creatinine, urine protein, and WBC are obtained prior to each dose. If proteinuria is noted, administer IV hydration and repeat the test.
• If patient is taking zidovudine, ensure that zidovudine is either discontinued or reduce dose by 50% on days of cidofovir infusion.
• Ensure that intraocular pressure, visual acuity, and ocular symptoms are periodically monitored.
• Administer 2 g probenecid 3 hr before IV dose, and 1 g at 2 and 8 hr after the dose. Administer with food if patient experiences probenecid-induced nausea or vomiting. If nausea or vomiting persist, notify health care provider. An antiemetic may need to be prescribed.
• Administer 1 L of Normal Saline over a 1 to 2 hr period immediately before cidofovir dose. Ensure that a second L of Normal Saline is infused during or after the cidofovir dose if the patient can tolerate it.
• Monitor patient for allergic reaction to probenecid. Notify health care provider if suspected. Prophylactic antihistamine may be needed.

  Patient/Family Education:

• 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 hr before and 1 g 2 hr and 8 hr 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 side effects to health care provider.
• Inform patient of the major toxicities of cidofovir, ie, renal 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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