No

Antiviral Agent, Ophthalmic

Treatment of herpes zoster (shingles) in immunocompetent patients; episodic treatment or prophylaxis of recurrent genital herpes in immunocompetent patients; for first episode genital herpes

B

Clinical effects on the fetus: Teratogenicity registry, thus far, has shown no increased rate of birth defects than that of the general population; however, the registry is small and use during pregnancy is only warranted if the potential benefit to the mother justifies the risk of the fetus

Breast-feeding/lactation: Avoid use in breast-feeding, if possible, since the drug distributes in high concentrations in breast milk

Hypersensitivity to the drug or any component

Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome has occurred in immunocompromised patients; use caution and adjust the dose in elderly patients or those with renal insufficiency; safety and efficacy in children have not been established

>10%:

Central nervous system: Headache (13% to 17%)

Gastrointestinal: Nausea (8% to 16%)

1% to 10%:

Central nervous system: Dizziness (2% to 4%)

Dermatologic: Pruritus

Gastrointestinal: Diarrhea (4% to 5%), constipation (1% to 5%), abdominal pain (2% to 3%), anorexia ( less than or equal to 3%), vomiting ( less than or equal to 7%)

Neuromuscular & skeletal: Weakness (2% to 4%)

Ocular: Photophobia

Symptoms of overdose include elevated serum creatinine, renal failure, and encephalitis, precipitation in renal tubules

Hemodialysis has resulted in up to 60% reduction in serum acyclovir levels after administration of acyclovir

Decreased toxicity: Cimetidine and/or probenecid has decreased the rate but not the extent of valacyclovir conversion to acyclovir

Valacyclovir is rapidly and nearly completely converted to acyclovir by intestinal and hepatic metabolism. Acyclovir is converted to acyclovir monophosphate by virus-specific thymidine kinase then further converted to acyclovir triphosphate by other cellular enzymes. Acyclovir triphosphate inhibits DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase and being incorporated into viral DNA.

Distribution: Acyclovir is widely distributed throughout the body including brain, kidney, lungs, liver, spleen, muscle, uterus, vagina, and CSF

Protein binding: Valacyclovir is 13.5% to 17.9% bound to human plasma proteins

Metabolism: Valacyclovir is rapidly and nearly completely converted to acyclovir and elvalene by first pass intestinal and/or hepatic metabolism; acyclovir is hepatically metabolized to a very small extent

Bioavailability: After administration of valacyclovir, bioavailability of acyclovir is ~55%

Half-life: Normal renal function: Adults: 2.5-3.3 hours (acyclovir), approximately 30 minutes (valacyclovir); half-life of acyclovir in end-stage renal disease: 14-20 hours

Elimination: Primary route of acyclovir is the kidney

Oral: Adults:

Genital herpes:

Episodic treatment: 500 mg twice daily for 5 days

Prophylaxis: 500-1000 mg once daily

Dosing interval in renal impairment:

Cl_cr 30-49 mL/minute: 1 g every 12 hours

Cl_cr 10-29 mL/minute: 1 g every 24 hours

Cl_cr <10 mL/minute: 500 mg every 24 hours

Hemodialysis: 33% removed during 4-hour session

Urinalysis, BUN, serum creatinine, liver enzymes, and CBC

May cause dizziness

None reported

No information available to require special precautions

No effects or complications reported

Begin use as soon as possible following development of signs of herpes zoster. Take with plenty of fluids. May take without regard to meals.

Observe for CNS changes; avoid dehydration; begin therapy at the earliest sign of zoster infection (within 48 hours of the rash)

Caplets: 500 mg, 1000 mg

Acosta EP and Fletcher CV, "Valacyclovir," Ann Pharmacother, 1997, 31(2):185-91.

Alrabiah FA and Sacks SL, "New Antiherpesvirus Agents. Their Targets and Therapeutic Potential," Drugs, 1996, 52(1):17-32.

Beutner KR, Friedman DJ, Forszpaniak C, et al, "Valacyclovir Compared With Acyclovir for Improved Therapy for Herpes Zoster in Immunocompetent Adults," Antimicrob Agents Chemother, 1995, 39(7):1546-53.

Bodsworth NJ, Crooks RJ, Borelli S, et al, "Valaciclovir Versus Aciclovir in Patients Initiated Treatment of Recurrent Genital Herpes: A Randomized, Double-Blind Clinical Trial. International Valaciclovir HSV Study Group," Genitourin Med, 1997, 73(2):110-6.

Grant DM, Mauskopf JA, Bell L, et al, "Comparison of Valaciclovir and Acyclovir for the Treatment of Herpes Zoster in Immunocompetent Patients Over 50 Years of Age: A Cost-Consequence Model," Pharmacotherapy, 1997, 17(2):333-41.

Patel R, Bodsworth NJ, Woolley P, et al, "Valaciclovir for the Suppression of Recurrent Genital HSV Infection: A Placebo Controlled Study of Once Daily Therapy. International Valaciclovir HSV Study Group," Genitourin Med, 1997, 73(2):105-9.

Perry CM and Faulds D, "Valaciclovir. A Review of Its Antiviral Activity, Pharmacokinetic Properties and Therapeutic Efficacy in Herpesvirus Infections," Drugs, 1996, 52(5):754-72.

Reitano M, Tyring S, Lang W, et al, "Valaciclovir for the Suppression of Recurrent Genital Herpes Simplex Virus Infection: A Large-Scale Dose Range-Finding Study. International Valaciclovir HSV Study Group," J Infect Dis, 1998, 178(3):603-10.

Tyring SK, Douglas JM Jr, Corey L, et al, "A Randomized, Placebo-Controlled Comparison of Oval Valacyclovir and Acyclovir in Immunocompetent Patients With Recurrent Genital Herpes Infections. The Valaciclovir International Study Group," Arch Dermatol, 1998, 134(2):185-91.

"Valacyclovir," Med Lett Drugs Ther, 1996, 38(965):3-4.

Weller S, Blum MR, Doucette M, et al, "Pharmacokinetics of the Acyclovir Pro-Drug Valaciclovir After Escalating Single- and Multiple-Dose Administration to Normal Volunteers," Clin Pharmacol Ther, 1993, 54(6):595-605.