Usual Adult Dose for CMV Retinitis

Induction therapy:
5 mg/kg IV infusion every 12 hours for 14 to 21 days

Maintenance:
5 mg/kg IV infusion once a day for 7 days/week OR 6 mg/kg IV infusion once a day for 5 days/week.

Comments:

• IV infusion should be administered at a constant rate for over 1 hour; infusion instructions should be followed closely to avoid phlebitis/pain at infusion site.
• Laboratory testing should be performed prior to initiating treatment (e.g., CBC with differential and platelet counts, renal function, pregnancy testing in females of

reproductive potential).

• Patients should undergo frequent ophthalmological examinations during therapy.

Use: For the treatment of cytomegalovirus (CMV) retinitis in immunocompromised patients, including patients with acquired immunodeficiency syndrome (AIDS).

Usual Adult Dose for CMV Prophylaxis

Induction therapy:
5 mg/kg IV infusion every 12 hours for 14 to 21 days

Maintenance:
5 mg/kg IV infusion once a day for 7 days/week OR 6 mg/kg IV infusion once a day for 5 days/week.

Comments:

• IV infusion should be administered at a constant rate for over 1 hour; infusion instructions should be followed closely to avoid phlebitis/pain at infusion site.
• Laboratory testing should be performed prior to initiating treatment (e.g., CBC with differential and platelet counts, renal function, pregnancy testing in females of

reproductive potential).

Use for the prevention of cytomegalovirus (CMV) disease in transplant recipients at risk for CMV disease.

Usual Pediatric Dose for CMV Infection

Birth to 2 months: 6 mg/kg IV infusion every 12 hours
Duration of treatment: 6 months; however, most or all treatment should be accomplished with oral valganciclovir

Comments:

• IV ganciclovir therapy should be reserved for infants with symptomatic congenital CMV disease; therapy is not appropriate for infants with asymptomatic congenital CMV infection.
• IV therapy should be limited to infants unable to absorb oral therapy reliably from the gastrointestinal tract due to necrotizing enterocolitis or other bowel disorders; 6 mg/kg IV provides systemic ganciclovir exposure equivalent to that of 16/mg/kg oral valganciclovir .
• Significant neutropenia can occur; absolute neutrophil counts should be performed weekly for 6 weeks, then monthly starting at 8 weeks for the duration of antiviral therapy.
• For preterm infants with perinatally acquired CMV infection and symptomatic end-organ disease (pneumonitis, hepatitis, thrombocytopenia), it may be reasonable (although not specifically studied) to treat with IV ganciclovir for 2 weeks, reassess responsiveness to therapy, and if clinical benefit is realized, consider an additional 1 to 2 weeks more of therapy.
• Safety and efficacy of ganciclovir has not been established in pediatric patients; use should be considered off-label.

Use: For symptomatic congenital CMV disease.

Renal Dose Adjustments

CrCl 10 to 24 mL/min:
Induction: 1.25 mg/kg IV infusion every 24 hours
Maintenance: 0.625 mg/kg IV infusion every 24 hours

CrCl 25 to 49 mL/min:
Induction: 2.5 mg/kg IV infusion every 24 hours.
Maintenance: 1.25 mg/kg IV infusion every 24 hours

CrCl 50 to 69 mL/min:
Induction: 2.5 mg/kg IV infusion every 12 hours

Liver Dose Adjustments

No adjustment recommended

Dose Adjustments

Elderly: Renal function should be monitored and doses adjusted accordingly.

Precautions

US BOXED WARNINGS: HEMATOLOGIC TOXICITY, IMPAIRMENT OF FERTILITY, FETAL TOXICITY, MUTAGENESIS, AND CARCINOGENESIS:

• Hematologic Toxicity: Granulocytopenia, anemia, thrombocytopenia, and pancytopenia have been reported in patients treated with this drug.
• Impairment of Fertility: Based on animal data, this drug may cause temporary or permanent inhibition of spermatogenesis in males and suppression of fertility in females.
• Fetal Toxicity: Based on animal data, this drug has the potential to cause birth defects in humans.
• Mutagenesis and Carcinogenesis: Based on animal data, this drug has the potential to cause cancers in humans.

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Dose should be given shortly after completion of hemodialysis session since hemodialysis has been shown to reduce plasma levels by approximately 50%

CrCl less than 10 mL/min receiving hemodialysis:
Induction: 1.25 mg/kg IV infusion 3 times a week following hemodialysis
Maintenance: 0.625 mg/kg IV infusion 3 times a week following hemodialysis

Other Comments

Administration Advice:

• For IV infusion at a constant rate over 1 hour, preferably via plastic cannula into a vein with adequate blood flow to permit rapid dilution and distribution
• Administration should be accompanied by adequate hydration
• Do not administer by IV bolus as increased toxicity due to high plasma concentrations may occur; do not administer IM or subcutaneously as it may result in severe tissue irritation due to high pH

Reconstitution:

• Reconstitute with sterile water for injection; do not use bacteriostatic water containing parabens as it is incompatible and may cause precipitation.
• Gently swirl vial to ensure complete wetting of product; continue swirling until clear solution is obtained.
• Reconstituted solution is stable in vial at room temperature (25C) for 12 hours; do not refrigerate or freeze.

Infusion:

• Prepare infusion by adding appropriate volume of reconstituted solution to acceptable infusion fluid (typically 100 mL); 0.9% Sodium chloride, 5% Dextrose, Ringer's injection and Lactated Ringer's Injection have been found to be chemically and physically compatible.
• Infusion concentrations greater than 10 mg/mL are not recommended.
• Diluted solution should be refrigerated (2C to 8C) and used within 24 hours; do not freeze

Handling and Disposal:

• Solutions are alkaline (pH 11); avoid direct contact with skin or mucous membranes; if contact occurs, wash thoroughly with soap and water, rinse eye thoroughly with plain water; wearing disposable gloves and safety glasses is recommended.
• Because this drug shares some of the properties of antitumor agents, it should be handled and disposed of according to guidelines issued for antineoplastic drugs.

General:

• This drug is not a cure for CMV retinitis and progression of retinitis may occur during or following treatment; frequent ophthalmological follow-up examinations should occur during therapy.
• Official guidance on the appropriate use of antiviral agents should be consulted for most up-to-date guidance.

Monitoring:

• Prior to initiating therapy: Obtain complete blood count (CBC) with differential, platelet count, pregnancy test (in females of reproductive potential), renal function tests
• During therapy: Regularly monitor CBC with differential, platelet counts, and renal function; more frequent monitoring is recommended in patients with renal impairment, in patients who previously have had leukopenia with this drug or other nucleoside analogs, or in those whose neutrophil count was less than 1000 cell/microliter at baseline.
• CMV Retinitis: Patients should have frequent ophthalmological examinations to monitor disease status and for other retinal abnormalities

Patient advice:

• Patients should understand that this drug may cause hematologic toxicity and their blood counts should be closely monitored during treatment.
• Patients should understand that this drug should be considered a potential carcinogen.
• Both male and female patients should use effective contraception while receiving this drug and for a period of time after therapy has stopped; mothers should not breastfeed while taking this drug.
• Patients should speak with their healthcare provider if they start or stop any new medications including over the counter medications.
• Patients should be instructed not to drive as there are potential side effects that may affect cognitive abilities including seizures, dizziness and/or confusion.