Valcyte tablets are indicated for the treatment of cytomegalovirus (CMV) retinitis in patients with acquired immunodeficiency syndrome (AIDS) (see CLINICAL TRIALS ).

Valcyte is indicated for the prevention of cytomegalovirus (CMV) disease in kidney, heart, and kidney-pancreas transplant patients at high risk (Donor CMV seropositive/Recipient CMV seronegative [(D+/R-)]).

Valcyte is not indicated for use in liver transplant patients (see CLINICAL TRIALS and WARNINGS ).

The safety and efficacy of Valcyte for the prevention of CMV disease in other solid organ transplant patients such as lung transplant patients have not been established.

CLINICAL TRIALS

Induction Therapy of CMV Retinitis

Study WV15376

In a randomized, open-label controlled study, 160 patients with AIDS and newly diagnosed CMV retinitis were randomized to receive treatment with either Valcyte tablets (900 mg twice daily for 21 days, then 900 mg once daily for 7 days) or with intravenous ganciclovir solution (5 mg/kg twice daily for 21 days, then 5 mg/kg once daily for 7 days). Study participants were: male (91%), White (53%), Hispanic (31%), and Black (11%). The median age was 39 years, the median baseline HIV-1 RNA was 4.9 log₁₀, and the median CD₄ cell count was 23 cells/mm³. A determination of CMV retinitis progression by the masked review of retinal photographs taken at baseline and week 4 was the primary outcome measurement of the 3-week induction therapy. Table 4 provides the outcomes at 4 weeks.

Maintenance Therapy of CMV Retinitis

No comparative clinical data are available on the efficacy of Valcyte for the maintenance therapy of CMV retinitis because all patients in study WV15376 received open-label Valcyte after week 4. However, the AUC for ganciclovir is similar following administration of 900 mg Valcyte tablets once daily and 5 mg/kg intravenous ganciclovir once daily. Although the ganciclovir C_max is lower following Valcyte administration compared to intravenous ganciclovir, it is higher than the C_max obtained following oral ganciclovir administration (see Figure 1 in CLINICAL PHARMACOLOGY ). Therefore, use of Valcyte as maintenance therapy is supported by a plasma concentration-time profile similar to that of two approved products for maintenance therapy of CMV retinitis.

Prevention of CMV Disease in Heart, Kidney, Kidney-Pancreas, and Liver Transplantation

A double-blind, double-dummy active comparator study was conducted in 372 heart, liver, kidney, and kidney-pancreas transplant patients at high-risk for CMV disease (D+/R-). Patients were randomized (2 Valcyte: 1 oral ganciclovir) to receive either Valcyte (900 mg once daily) or oral ganciclovir (1000 mg three times a day) starting within 10 days of transplantation until Day 100 posttransplant. The proportion of patients who developed CMV disease, including CMV syndrome and/or tissue-invasive disease during the first 6 months posttransplant was similar between the Valcyte arm (12.1%, N=239) and the oral ganciclovir arm (15.2%, N=125). However, in liver transplant patients, the incidence of tissue-invasive CMV disease was significantly higher in the Valcyte group compared with the ganciclovir group. These results are summarized in Table 5 .

Mortality at six months was 3.7% (9/244) in the Valcyte group and 1.6% (2/126) in the oral ganciclovir group.

Valcyte tablets are administered orally, and should be taken with food (see CLINICAL PHARMACOLOGY: Absorption ). After oral administration, valganciclovir is rapidly and extensively converted into ganciclovir. The bioavailability of ganciclovir from Valcyte tablets is significantly higher than from ganciclovir capsules. Therefore the dosage and administration of Valcyte tablets as described below should be closely followed (see PRECAUTIONS: General and OVERDOSAGE ).

For patients who have received a kidney, heart, or kidney-pancreas transplant, the recommended dose is 900 mg (two 450 mg tablets) once daily with food starting within 10 days of transplantation until 100 days posttransplantation.

Serum creatinine or creatinine clearance levels should be monitored carefully. Dosage adjustment is required according to creatinine clearance as shown in Table 13 (see PRECAUTIONS: General and CLINICAL PHARMACOLOGY: Special Populations: Renal Impairment ). Increased monitoring for cytopenias may be warranted in patients with renal impairment (see PRECAUTIONS: Laboratory Testing ).

For females = 0.85 x male value

Valcyte should not be prescribed to patients receiving hemodialysis (see CLINICAL PHARMACOLOGY: Special Populations: Hemodialysis and PRECAUTIONS: General ).

For patients on hemodialysis (CrCl <10 mL/min) a dose recommendation cannot be given (see CLINICAL PHARMACOLOGY: Special Populations: Hemodialysis ).

Caution should be exercised in the handling of Valcyte tablets. Tablets should not be broken or crushed. Since valganciclovir is considered a potential teratogen and carcinogen in humans, caution should be observed in handling broken tablets (see WARNINGS: Teratogenesis, Carcinogenesis and Mutagenesis ). Avoid direct contact of 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 (ie, 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 (see REFERENCES ).

There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate.

Valcyte (valganciclovir HCl tablets) is available as 450 mg pink convex oval tablets with "VGC" on one side and "450" on the other side. Each tablet contains valganciclovir HCl equivalent to 450 mg valganciclovir. Valcyte is supplied in bottles of 60 tablets (NDC 0004-0038-22).

Store at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F) [See USP controlled room temperature].

1. Recommendations for the Safe Handling of Cytotoxic Drugs. US Department of Health and Human Services, National Institutes of Health, Bethesda, MD, September 1992. NIH Publication No. 92-2621

2. American Society of Hospital Pharmacists technical assistance bulletin on handling cytotoxic and hazardous drugs. Am J Hosp Pharm. 1990; 47:1033-1049

3. Controlling Occupational Exposures to Hazardous Drugs. US Department of Labor. Occupational Health and Safety Administration. OSHA Technical Manual. Section VI - Chapter 2, January 20, 1999

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