Usual Adult Dose for CMV Retinitis

Induction dose: 900 mg orally twice a day for 21 days
Maintenance dose: 900 mg orally once a day

Comments:

• The tablet formulation should be used, not the oral solution.
• The maintenance dose should be used after the induction dose or in patients with inactive CMV retinitis.

Use: For the treatment of CMV retinitis in patients with AIDS

Usual Adult Dose for CMV Prophylaxis

900 mg orally once a day

Duration of therapy:

• Heart or kidney-pancreas transplant patients: Until 100 days posttransplantation.
• Kidney transplant patients: Until 200 days posttransplantation.

Comments:

• The tablet formulation should be used, not the oral solution.
• Therapy should be started within 10 days of transplantation.

Use: For the prevention of CMV disease in kidney, heart, and kidney-pancreas transplant recipients at high risk (donor CMV seropositive/recipient CMV seronegative)

Usual Pediatric Dose for CMV Prophylaxis

1 month to 16 years (heart transplant recipients) or 4 months to 16 years (kidney transplant recipients):
The recommended once-daily oral dose is based on BSA and CrCl derived from a modified Schwartz formula, and is calculated using the following equation:

Pediatric dose (mg) = 7 x BSA x CrCl (calculated using a modified Schwartz formula)

• If the calculated Schwartz CrCl exceeds 150 mL/min/1.73 m2, then a maximum value of 150 mL/min/1.73 m2 should be used in the equation.

Mosteller BSA (m2) = the square root of (height [cm] x weight [kg] divided by 3600)

Schwartz CrCl (mL/min/1.73 m2) = k x height (cm) divided by serum creatinine (mg/dL)

k values:

• Infants less than 1 year of age with low birth weight for gestational age: 0.33
• Infants less than 1 year of age with birth weight appropriate for gestational age: 0.45
• Children aged 1 to less than 2 years: 0.45
• Boys aged 2 to less than 13 years and girls aged 2 to less than 16 years: 0.55
• Boys aged 13 to 16 years: 0.7

Maximum dose: 900 mg orally once a day

Older than 16 years: 900 mg orally once a day

Duration of therapy:

• Heart transplant patients (1 month or older): Until 100 days posttransplantation.
• Kidney transplant patients (4 months or older): Until 200 days posttransplantation.
• Kidney-pancreas transplant patients (older than 16 years): Until 100 days posttransplantation.

Comments:

• The recommended once-daily dose should be started within 10 days of transplantation.
• The k values provided are based on the Jaffe method of measuring serum creatinine; correction may be necessary when enzymatic methods are used.
• During prophylaxis, the calculated dose should be adjusted as appropriate; serum creatinine levels should be monitored regularly and changes in height and body weight should be considered.
• All calculated doses should be rounded to the nearest 10 mg increment for actual deliverable dose, up to maximum dose of 900 mg.
• The oral solution is the preferred formulation for patients 1 month to 16 years; it provides the ability to administer a dose calculated according to the formula above. The tablets may be used if the calculated doses are within 10% of available tablet strength (450 mg); for example, one 450 mg tablet may be used for calculated doses between 405 mg and 495 mg.
• The oral solution should be used for patients 1 month to 16 years unable to reliably swallow a tablet.
• Patients older than 16 years should use the tablet formulation, not the oral solution.

Uses: For the prevention of CMV disease:

• In heart transplant recipients (1 month or older) at high risk
• In kidney transplant recipients (4 months or older) at high risk
• In kidney-pancreas transplant recipients (older than 16 years) at high risk

Usual Pediatric Dose for CMV Retinitis

Older than 16 years:
Induction dose: 900 mg orally twice a day for 21 days
Maintenance dose: 900 mg orally once a day

Comments:

• The tablet formulation should be used, not the oral solution.
• The maintenance dose should be used after the induction dose or in patients with inactive CMV retinitis.

Use: For the treatment of CMV retinitis in patients with AIDS

Renal Dose Adjustments

Adults and adolescents older than 16 years:
CrCl 40 to 59 mL/min:

• Induction dose: 450 mg orally twice a day
• Maintenance/prevention dose: 450 mg orally once a day

CrCl 25 to 39 mL/min:

• Induction dose: 450 mg orally once a day
• Maintenance/prevention dose: 450 mg orally every 2 days

CrCl 10 to 24 mL/min:

• Induction dose: 450 mg orally every 2 days
• Maintenance/prevention dose: 450 mg orally twice a week

Pediatrics: Dosing in pediatric patients with renal dysfunction can be done using the recommended equations as CrCl is a component in the calculation.

Comments: Serum creatinine levels or CrCl should be monitored regularly during therapy; dose should be adjusted as appropriate.

Liver Dose Adjustments

Data not available

Comments: Safety and efficacy have not been established in patients with liver dysfunction.

Precautions

US BOXED WARNINGS:

• FETAL TOXICITY: Based on animal data, this drug has the potential to cause birth defects in humans.
• HEMATOLOGIC TOXICITY: Severe leukopenia, neutropenia, anemia, thrombocytopenia, pancytopenia, bone marrow failure, including aplastic anemia reported 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.
• MUTAGENESIS AND CARCINOGENESIS: Based on animal data, this drug has the potential to cause cancers in humans.

Safety and efficacy have not been established for children (up to 16 years) for prevention of CMV disease in pediatric liver transplant patients, in heart transplant patients younger than 1 month, in kidney transplant patients younger than 4 months, in pediatric AIDS patients with CMV retinitis, or in infants with congenital CMV infection.

Consult WARNINGS section for additional precautions.

Dialysis

Adults and adolescents older than 16 years:
Hemodialysis (CrCl less than 10 mL/min): Not recommended.

Comments: A reduced dose of ganciclovir is recommended; the manufacturer product information for ganciclovir should be consulted.

Other Comments

Administration advice:

• Administer with food.
• Use the tablet formulation in adults and adolescents older than 16 years, not the oral solution.
• Do not break or crush tablets.
• Use caution when handling this drug (tablets or oral solution).

Storage requirements:

• Oral solution (dry powder), tablets: Store at 25C (77F); excursions permitted to 15C to 30C (59F to 86F).
• Oral solution (constituted): Store under refrigeration at 2C to 8C (36F to 46F) for no longer than 49 days; do not freeze.

Reconstitution/preparation techniques:

• The oral solution must be prepared by a pharmacist before it is dispensed.
• The manufacturer product information should be consulted.

General:

• Broken/crushed tablets, the powder for oral solution, and the constituted oral solution should be handled with caution; direct contact with skin or mucous membranes should be avoided. If direct contact occurs, the area should be washed thoroughly with soap and water; eyes should be rinsed thoroughly with plain water.
• This drug should be handled and disposed of according to guidelines for antineoplastic agents.

Monitoring:

• Hematologic: Complete blood counts with differential and platelet counts (frequently during therapy); for cytopenias
• Ocular: Ophthalmologic follow-up examinations in patients with CMV retinitis (at least every 4 to 6 weeks during therapy)
• Renal: Serum creatinine levels or CrCl (frequently during therapy); renal function in elderly patients (before and during therapy)

Patient advice:

• Maintain adequate hydration.
• Use the dosing dispensers provided with the oral solution.
• Read the US FDA-approved patient product information (Patient Information and Instructions for Use).
• Convulsions, sedation, dizziness, ataxia, and confusion reported with this drug; may affect ability to drive and operate machinery.