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Valganciclovir hydrochloride (Valcyte^®) (C₁₄H₂₂N₆O₄.HCl; MWt=390.83) is the HCl salt of the L-valyl ester of ganciclovir, which is a synthetic 2'-deoxy-guanosine analogue used for the prevention and treatment cytomegalovirus (CMV) infections in immunocompromized or immunosuppressed patients.
Valganciclovir is the prodrug for ganciclovir. After oral administration, it is rapidly converted to ganciclovir by intestinal and hepatic esterases. Here is more on ganciclovir.

The FDA approved indication for valganciclovir is the treatment of CMV retinitis in AIDS patients.

• Following oral administration, valganciclovir is rapidly hydrolyzed to ganciclovir by esterases in the intestinal and hepatic cells.
• Absolute oral bioavailability is approximately 60%. When taken with food, a 900-mg dose of valganciclovir is essentially equivalent to an IV ganciclovir dose of 5 mg/kg. High fat food significantly increases the bioavailability and the peak serum level.
• The time to maximum serum concentration (C_max) is approximately 2 hours.
• The C_max following the administration of 900 mg of valganciclovir to adult patients with normal renal function is 5.6 and the serum level at 12 hours after the dose is about 1 µg/mL. In vitro CMV resistance is defined as an IC₅₀³1.5 µg/mL.
• The plasma protein binding of ganciclovir is £2%, and its volume of distribution is approximately 0.7 L/kg.
• Liver transplant recipients attained similar exposures to ganciclovir following the administration of 900 mg of valganciclovir and 5 mg/kg IV ganciclovir (42 vs 48 µg.hr/mL).
• Valganciclovir is eliminated as ganciclovir in the urine via glomerular filtration and active tubular secretion. The renal clearance of ganciclovir is approximately 3 mL/min/kg.
• The elimination half-life of ganciclovir is about 4 hrs in patients with a creatinine clearance (CLcr) >75 mL/min, and approximately 24 hrs in patients with CLcr between 10 and 20 mL/min.
  

• Ganciclovir (and valganciclovir) can cause granulocytopenia (neutropenia), anemia, and thrombocytopenia.
• In animal studies ganciclovir was found to be carcinogenic, teratogenic, and caused aspermatogenesis.
• Valganciclovir is contraindicated in patients with hypersensitivity to ganciclovir or valganciclovir.
• Valganciclovir is contraindicated in patients with:
  • Absolute neutrophil count < 500 cells/µL.
  • Platelet count < 25,000 platelets/µL.
  • Hemoglobin concentration < 8 grams/dL.
• Valganciclovir should be used with caution in patients with renal failure and the dose should be adjusted based on the estimated creatinine clearance (see Dose and Administration below).

450-mg tablets (pink; NDC = 00004-0038-22)
Valganciclovir tablets can be used to extemporaneously prepare an oral liquid for patients who cannot swallow the tablets.

• 900 mg of valganciclovir PO q12h is equivalent to 5 mg/kg IV ganciclovir q12h
• Valganciclovir dosage should be adjusted based on the estimated creatinine clearance to prevent the accumulation of ganciclovir and associated toxicities. The following table represents the manufacturer's recommendations:

  Valganciclovir Dose Modifications for Patients with Renal Impairment
  CLcr (mL/min)	Induction	Maintenance
  ³60	900 mg q12h	900 mg q24h
  40 - 59	450 mg q12h	450 mg q24h
  25 - 39	450 mg q24h	450 mg q48h
  10 - 24	450 mg q48h	450 mg twice/wk

• Hematologic: neutropenia, anemia, and thrombocytopenia.
• GI problems: diarrhea, nausea, vomiting, and abdominal pain.
• CNS: Fever, headache, insomnia, paresthesia, and peripheral neuropathy.
• Retinal detachment.

• No in vivo drug-drug interaction studies were conducted with valganciclovir. However, extrapolation from IV ganciclovir studies is justified.
• Probencid and other drugs secreted by renal organic anion transport system are likely to reduce ganciclovir clearance ð ganciclovir accumulation ð ñ risk of toxicity
• Coadministration with other myelosuppressive agents (e.g., zidovudine, MMF, azathiprine, etc) ð ñ risk of toxicity
• Ganciclovir ð ñ didanosine bioavailability by 22 to 110%.

1. Valcyte PI
2. Paltiel AD et al Preevaluation of clinical trial data: the case of preemptive cytomegalovirus therapy in patients with human immunodeficiency virus. Clin Infect Dis. 2001;32(5):783-93.
3. Pescovitz MD et al Valganciclovir results in improved oral absorption of ganciclovir in liver transplant recipients. Antimicrob Agents Chemother. 2000;44(10):2811-5.
4. Reusser P. Antiviral therapy: current options and challenges. Schweiz Med Wochenschr. 2000;130(4):101-12.
5. Sugawara M, Huang W, Fei YJ, et al. Transport of valganciclovir, a ganciclovir prodrug, via peptide transporters PEPT1 and PEPT2. J Pharm Sci. 2000;89(6):781-9.
6. Michael M. POSITION PAPER regarding approval of HOFFMANN-LA ROCHE'S valganciclovir for the treatment of cytomegalovirus (CMV) retinitis in patients with AIDS.