General Dosing Information

• Adult patients should use VALCYTE tablets, not VALCYTE for oral solution.
• VALCYTE for oral solution and tablets should be taken with food [see Clinical Pharmacology (12.3)].
• VALCYTE for oral solution (50 mg/mL) must be prepared by the pharmacist prior to dispensing to the patient [see Dosage and Administration (2.4)].

Recommended Dosage in Adult Patients with Normal Renal Function

For dosage recommendations in adult patients with renal impairment [see Dosage and Administration (2.5)].

Recommended Dosage in Pediatric Patients

Prevention of CMV Disease in Pediatric Heart Transplant Patients: For pediatric heart transplant patients 1 month to 16 years of age, the recommended once daily mg dose (7 × BSA × CrCl) should start within 10 days of transplantation until 100 days post-transplantation.

The recommended once daily dosage of VALCYTE is based on body surface area (BSA) and creatinine clearance (CrCl) derived from a modified Schwartz formula, and is calculated using the equation below:

Pediatric Dose (mg) = 7 × BSA × CrCl (calculated using a modified Schwartz formula). If the calculated Schwartz creatinine clearance exceeds 150 mL/min/1.73m2, then a maximum value of 150 mL/min/1.73m2 should be used in the equation. The k values used in the modified Schwartz formula are based on pediatric patient age, as shown in Table 1.

Schwartz Creatinine Clearance (mL / min / 1.73m2) =	k × Height (cm)
	Serum Creatinine (mg / dL)

Table 1 k Values According to Pediatric Patient Age *

k value	Pediatric Patient Age
0.33	Infants less than 1 year of age with low birth weight for gestational age
0.45	Infants less than 1 year of age with birth weight appropriate for gestational age
0.45	Children aged 1 to less than 2 years
0.55	Boys aged 2 to less than 13 years Girls aged 2 to less than 16 years
0.7	Boys aged 13 to 16 years

Monitor serum creatinine levels regularly and consider changes in height and body weight and adapt the dose as appropriate during prophylaxis period.

All calculated doses should be rounded to the nearest 25 mg increment for the actual deliverable dose. The oral dispenser is graduated in 0.5 mL increments. A 50 mg dose is equivalent to 1 mL. If the calculated dose exceeds 900 mg, a maximum dose of 900 mg should be administered. VALCYTE for oral solution is the preferred formulation since it provides the ability to administer a dose calculated according to the formula above; however, VALCYTE tablets may be used if the calculated doses are within 10% of available tablet strength (450 mg). For example, if the calculated dose is between 405 mg and 495 mg, one 450 mg tablet may be taken. Before prescribing VALCYTE tablets, pediatric patients should be assessed for the ability to swallow tablets.

Preparation of VALCYTE for Oral Solution

Wearing disposable gloves is recommended during reconstitution and when wiping the outer surface of the bottle/cap and the table after reconstitution. Prior to dispensing to the patient, VALCYTE for oral solution must be prepared by the pharmacist as follows [see How Supplied/Storage and Handling (16)]:

• Measure 91 mL of purified water in a graduated cylinder.
• Shake the VALCYTE bottle to loosen the powder. Remove the child resistant bottle cap and add approximately half the total amount of water for constitution to the bottle and shake the closed bottle well for about 1 minute. Add the remainder of water and shake the closed bottle well for about 1 minute. This prepared solution contains 50 mg of valganciclovir free base per 1 mL.
• Remove the child resistant bottle cap and push the bottle adapter into the neck of the bottle.
• Close bottle with child resistant bottle cap tightly. This will assure the proper seating of the bottle adapter in the bottle and child resistant status of the cap.
• Store constituted oral solution under refrigeration at 2°C to 8°C (36°F to 46°F) for no longer than 49 days. Do not freeze.
• Write the discard date of the constituted oral solution on the bottle label.

The patient package insert, which includes the dosing instructions for patients, and 2 oral dispensers should be dispensed to the patient [see Patient Counseling Information (17)].

Dosage Recommendation for Adult Patients with Renal Impairment

Serum creatinine levels or estimated creatinine clearance should be monitored regularly during treatment. Dosage recommendations for adult patients with reduced renal function are provided in Table 2. For adult patients on hemodialysis (CrCl less than 10 mL/min), a dose recommendation for VALCYTE cannot be given [see Use in Specific Populations (8.5, 8.6), Clinical Pharmacology (12.3)].

*An estimated creatinine clearance in adults is calculated from serum creatinine by the following formulas:

For females = 0.85 × male value

Dosing in pediatric patients with renal impairment can be done using the recommended equations because CrCl is a component in the calculation [see Dosage and Administration (2.3)].

Handling and Disposal

Caution should be exercised in the handling of VALCYTE tablets and VALCYTE for oral solution. Tablets should not be broken or crushed. Because valganciclovir is considered a potential teratogen and carcinogen in humans, caution should be observed in handling broken tablets, the powder for oral solution, and the constituted oral solution [see Warnings and Precautions (5.4, 5.5)]. Avoid direct contact with broken or crushed tablets, the powder for oral solution, and the constituted oral solution with skin or mucous membranes. If such contact occurs, wash thoroughly with soap and water, and rinse eyes thoroughly with plain water.

Handle and dispose VALCYTE according to guidelines for antineoplastic drugs because ganciclovir shares some of the properties of antitumor agents (i.e., carcinogenicity and mutagenicity).2