Cytovene

Action

Inhibits binding of deoxyguanosine triphosphate to DNA polymerase by terminating DNA synthesis, thereby inhibiting viral replication

Availability

Capsules: 250 mg, 500 mg

Injection: 500 mg/vial

Intravitreal implant: 4.5 mg

Indications and dosages

➣ Prevention of CMV in advanced human immunodeficiency virus (HIV) infection

Adults: 1,000 mg P.O. t.i.d.

➣ Prevention of CMV in transplant recipients

Adults: 5 mg/kg I.V. q 12 hours for 7 to 14 days; then 5 mg/kg/day 7 days per week or 6 mg/kg/day 5 days per week

➣ CMV retinitis in immunocompromised patients

Adults and children ages 9 and older: Intravitreal implant (4.5 mg) placed during intraocular surgery

Adults and children older than 3 months: Initially, 5 mg/kg I.V. q 12 hours for 14 to 21 days, followed by a maintenance dosage of 5 mg/kg/day 7 days per week or 6 mg/kg 5 days per week. For P.O. maintenance, 1,000 mg P.O. t.i.d. or 500 mg P.O. q 3 hours while patient is awake.

Dosage adjustment

• Renal impairment

• Elderly patients

Off-label uses

• CMV gastroenteritis, CMV pneumonia

Contraindications

• Hypersensitivity to drug or acyclovir

• Neutropenia or thrombocytopenia

• Contraindications for intraocular surgery, such as external infections or thrombocytopenia (with intravitreal implant)

• Breastfeeding

Precautions

Use cautiously in:

• renal impairment

• history of cytopenic reactions

• pregnant patients

• children younger than age 9 (with intravitreal implant).

Administration

See Follow facility policy for handling and disposing of antineoplastic drugs. (Drug shares some properties with antitumor agents.)

• Be aware that safety and efficacy of I.V. use haven't been established for congenital or neonatal CMV disease, treatment of established CMV disease other than retinitis, or use in nonimmunocompromised individuals.

See Don't let powder in capsules or I.V. solution contact skin, eyes, or mucous membranes. If contact occurs, wash skin thoroughly with soap and water, or flush eyes with water.

• Reconstitute 500-mg vial with 10 ml of sterile water; shake vial to dissolve drug. Then dilute drug again in 50 to 250 ml of compatible I.V. solution.

• If patient is on fluid restriction, dilute to a concentration of 10 mg/ml or less.

See Administer a single dose by I.V. infusion slowly (over at least 1 hour), using infusion pump or microdrip (60 gtt/ml).

• Give I.V. solution within 24 hours of dilution to reduce risk of bacterial contamination.

See Don't give by I.V. bolus or by I.M. or subcutaneous route.

• Administer oral doses with food.

• Be aware that intravitreal implant is designed to release drug over 5 to 8 months. Once drug is depleted (as shown by retinitis progression), implant may be removed and replaced.

See Handle intravitreal implant carefully by suture tab only, to avoid damage to polymer coating. (Damage could increase rate of drug release.)

Adverse reactions

CNS: ataxia, confusion, dizziness, headache, drowsiness, tremor, abnormal thinking, agitation, amnesia, neuropathy, paresthesia, seizures, coma

CV: hypertension, hypotension, phlebitis, arrhythmias

EENT: vision loss for 2 to 4 weeks, vitreous loss, vitreous hemorrhage, cataract, retinal detachment, uveitis, endophthalmitis (all with intravitreal implant)

GI: nausea, vomiting, diarrhea, abdominal pain, dyspepsia, flatulence, anorexia, dry mouth

Hematologic: anemia, agranulocytosis, thrombocytopenia, leukopenia

Respiratory: pneumonia

Skin: rash, diaphoresis, pruritus

Other: fever; infection; chills; inflammation, pain, and phlebitis at injection site; sepsis

Interactions

Drug-drug. Amphotericin B, cyclosporine, other nephrotoxic drugs: increased risk of renal impairment and ganciclovir toxicity

Cilastatin, imipenem: increased seizure activity

Cytotoxic drugs: increased toxic effects

Immunosuppressants: increased immunologic and bone marrow depression

Probenecid: increased ganciclovir blood level

Zidovudine: increased risk of agranulocytosis

Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, creatinine, gamma-glutamyltransferase: increased values

Granulocytes, hemoglobin, neutrophils, platelets, white blood cells: decreased values

Liver function tests: abnormal results

Patient monitoring

• Monitor liver function test results.

• Monitor neutrophil and platelet counts.

• Assess fluid intake and output to ensure adequate hydration.

• Make sure patient has regular ophthalmic examinations during both induction and maintenance therapy.

See Monitor neurologic status closely; watch for seizures and coma.

See Check for signs and symptoms of infection, particularly sepsis.

Patient teaching

See Advise patient to immediately report signs and symptoms of infection, including those at infusion site.

See Instruct patient to immediately report easy bruising or bleeding.

• Instruct patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

• Caution female patient not to breastfeed.

• Inform patient that drug may cause birth defects. Tell females to use effective birth control during therapy; advise males to use barrier contraception during and for 90 days after therapy.

See Caution patient not to open or crush capsule. If powder from capsule contacts skin or eyes, tell him to wash skin thoroughly with soap and water or flush eyes with water.

• Instruct patient to minimize GI upset by eating frequent, small servings of healthy food.

• Tell patient he'll undergo regular blood testing during therapy.

• Explain that drug doesn't cure CMV retinitis and that patient should have eye exams every 4 to 6 weeks during therapy.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.