Valganciclovir

Valganciclovir (Valcyte, manufactured by Hoffmann–La Roche, and also known as Cymeval, Valcyt, Valixa, Darilin, Rovalcyte, Patheon, and Syntex ) is an antiviral medication used to treat cytomegalovirus infections. As the L -valyl ester of ganciclovir, it is actually a prodrug for ganciclovir. After oral administration, it is rapidly converted to ganciclovir by intestinal and hepatic esterases.

Administration
Orally, available in 450 mg tablets. For patients who have received a transplant, the recommended dose is 900 mg once daily, starting within 10 days of transplantation and continuing for 6 months post transplantation. HIV patients might initially need to take the dose 900 mg twice daily for the first 3 weeks.

Pharmacokinetics

 * 1) Oral bioavailability is approximately 60%. Fatty foods significantly increase the bioavailability and the peak level in the serum.
 * 2) It takes about 2 hours to reach maximum concentrations in the serum.
 * 3) Valganciclovir is eliminated as ganciclovir in the urine, with a half-life of about 4 hours in people with normal kidney function.
 * 4) The mechanism of this drug is activation via a viral protein kinase HCMV UL97 and subsequent phosphorylation by cellular kinases. The phosphotransferase enzyme can likewise activate valganciclovir.

Side effects

 * Blood: neutropenia, anemia, low platelets. Myelosuppression is one of the main side effects that may limit prolonged use of valganciclovir.
 * Gastrointestinal: diarrhea, nausea, vomiting, abdominal pain.
 * Central nervous system: fever, headache, insomnia, paresthesia, and peripheral neuropathy.
 * Ocular: retinal detachment

Alternative uses
It has been proposed that valganciclovir could be used in the treatment of chronic fatigue syndrome. In an initial, open-label trial, 12 patients with elevated antibody titers to human herpesvirus 6 (HHV-6) and Epstein-Barr virus (EBV) and who had suffered with neurocognitive symptoms and debilitating fatigue consistent with chronic fatigue syndrome were administered valganciclovir for six months. "Nine out of 12 (75%) patients experienced near resolution of their symptoms, allowing them all to return to the workforce or full time activites," accompanied in the same patients by falls in antibody titers to both viruses. The results of a follow-up double-blind, placebo-controlled study of 30 patients were ambiguous: overall scores on the Multidimensional Fatigue Inventory (MFS-20) were nominally higher in valganciclovir-treated patients vs. placebo, but the difference was not statistically significant; moreover, there were no differences in antibody titers between the two groups. However, in a secondary analysis, differences in several specific subscales of the score were significantly different between valganciclovir treatment and placebo.

Continuous treatment of cytomegalovirus infections with valganciclovir in patients with glioblastoma multiforme has shown to increase 2-year survival to 90% in a trial of 25 patients.

Price and patent status
Roche's Valcyte is protected by patent. However a generic version manufactured by Japanese-owned Indian company Daiichi-Ranbaxy was found by the District Court of New Jersey, USA not to infringe Roche's patent.

The price of a four-month course of valganciclovir from Roche is about US$8,500 in high-income countries, $6,000 in India. However, the valganciclovir patent was rejected by the Indian Patent Office in 2010, although Roche may appeal the rejection.