Valganciclovir

2.1 General Dosing Information • Valganciclovir tablets USP should be taken with food [see Clinical Pharmacology (12.3)]. • The bioavailability of ganciclovir from valganciclovir is significantly higher than from ganciclovir capsules. Therefore, valganciclovir tablets USP cannot be substituted for ganciclovir capsules on a one-to-one basis [see Clinical Pharmacology (12.3)]. • Adult patients should use valganciclovir tablets, not valganciclovir for oral solution. 2.2 Adult Patients With Normal Renal Function

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

Treatment of CMV Retinitis: Induction:

• The recommended dose is 900 mg (two 450 mg tablets) twice a day for 21 days. • Maintenance: Following induction treatment, or in adult patients with inactive CMV retinitis, the recommended dose is 900 mg (two 450 mg tablets) once a day.

Prevention of CMV Disease:

• For adult patients who have received a heart or kidney-pancreas transplant, the recommended dose is 900 mg (two 450 mg tablets) once a day starting within 10 days of transplantation until 100 days post-transplantation. • For adult patients who have received a kidney transplant, the recommended dose is 900 mg (two 450 mg tablets) once a day starting within 10 days of transplantation until 200 days post-transplantation. 2.3 Pediatric Patients

Prevention of CMV Disease: For pediatric patients 4 months to 16 years of age who have received a kidney or heart transplant, the recommended once daily dose of valganciclovir tablets USP starting within 10 days of transplantation until 100 days post-transplantation 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 x BSA x 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.

where k =

0.45 for patients aged 4 months to < 1 year,

0.45 for patients aged 1 to < 2 years (note k value is 0.45 instead of the typical value of 0.55),

0.55 for boys aged 2 to < 13 years and girls aged 2 to 16 years, and

0.7 for boys aged 13 to 16 years.

All calculated doses should be rounded to the nearest 25 mg increment for the actual deliverable dose. If the calculated dose exceeds 900 mg, a maximum dose of 900 mg should be administered. Valganciclovir for oral solution is the preferred formulation since it provides the ability to administer a dose calculated according to the formula above; however, valganciclovir tablets USP 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.

2.5 Renal Impairment

Dosage recommendations for adult patients with reduced renal function are provided in Table 1. For adult patients on hemodialysis (CrCl <10 mL/min), a dose recommendation for valganciclovir tablets cannot be given [see Use in Specific Populations (8.5, 8.6 ), Clinical Pharmacology (12.3)].

Table 1 Dosage Recommendations for Adult Patients with Impaired Renal Function

Valganciclovir 450 mg Tablets

CrCl*(mL/min)

Induction Dose

Maintenance/ Prevention Dose

≥ 60

900 mg twice daily

900 mg once daily

40 to 59

450 mg twice daily

450 mg once daily

25 to 39

450 mg once daily

450 mg every 2 days

10 to 24

450 mg every 2 days

450 mg twice weekly

< 10 (on hemodialysis)

not recommended

not recommended

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

For males=                              (140 – age [years]) x (body weight [kg])

                                                _______________________________

                                                  (72) x (serum creatinine [mg/dL])

For females= 0.85 x 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)].

2.6 Handling and Disposal

Caution should be exercised in the handling of valganciclovir tablets USP. 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, [see Warnings and Precautions (5.3, 5.4)]. Avoid direct contact with broken or crushed tablets with skin or mucous membranes. If such contact occurs, wash thoroughly with soap and water, and rinse eyes thoroughly with plain water.

Because ganciclovir shares some of the properties of antitumor agents (i.e., carcinogenicity and mutagenicity), consideration should be given to handling and disposal according to guidelines issued for antineoplastic drugs. Several guidelines on this subject have been published. However, there is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate [see References (15)].