INDICATION

Valmeg oral tablets are indicated for the prevention of CMV (cytomegalovirus) disease in kidney transplant patients.

MECHANISM OF ACTION

Man’s natural supply of vitamin D depends mainly on exposure to the ultraviolet rays of the sun for conversion of 7-dehydrocholesterol in the skin to vitamin D3 (cholecalciferol). Vitamin D3 must be metabolically activated in the liver and the kidney before it is fully active as a regulator of calcium and phosphorus metabolism at target tissues. The initial transformation of vitamin D3 is catalyzed by a vitamin D3-25-hydroxylase enzyme (25-OHase) present in the liver, and the product of this reaction is 25-hydroxyvitamin D3 [25-(OH)D3]. Hydroxylation of 25-(OH)D3occurs in the mitochondria of kidney tissue, activated by the renal 25-hydroxyvitamin D3-1 alpha-hydroxylase (alpha-OHase), to produce 1,25-(OH)2D3 (calcitriol), the active form of vitamin D3. Endogenous synthesis and catabolism of calcitriol, as well as physiological control mechanisms affecting these processes, play a critical role regulating the serum level of calcitriol. Physiological daily production is normally 0.5 to 1.0 mcg and is somewhat higher during periods of increased bone synthesis (e.g., growth or pregnancy).

Pharmacodynamics

Valganciclovir is an L-valylester (prodrug)ofganciclovir that exists as a mixture of two diastereomers.

In CMV-infected cells ganciclovir is initially phosphorylated to ganciclovir monophosphate by the viralprotein kinase, pUL97.

Further phosphorylation occurs by cellular kinases to produce ganciclovir triphosphate, which is thenslowly metabolized intracellularly (half-life 18 hours).

As the phosphorylation is largely dependent on the viral kinase, phosphorylation of ganciclovir occurs preferentially in virus-infected cells.

The virus static activity of gancicloviris due to inhibition of viral DNA synthesis by ganciclovirtriphosphate.

DOSAGE

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.

ADMINISTRATION

Valmeg is available as a 450 mg tablet for oral administration.