>10%: Central nervous system: Headache (14% to 35%)

1% to 10%:

Central nervous system: Dizziness (2% to 4%), depression (0% to 7%)

Endocrine: Dysmenorrhea (1% to 8%)

Gastrointestinal: Abdominal pain (2% to 11%), nausea (6% to 15%), vomiting (<1% to 6%)

Hematologic: Leukopenia (1%), thrombocytopenia (1%)

Hepatic: AST increased (1% to 4%)

Neuromuscular & skeletal: Arthralgia (1 to 6%)

<1%: Anemia

Postmarketing and/or case reports: Acute hypersensitivity reactions (angioedema, anaphylaxis, dyspnea, pruritus, rash, urticaria); aggression, agitation, alopecia, aplastic anemia, ataxia, creatinine increased, coma, confusion, consciousness decreased, diarrhea, dysarthria, encephalopathy, facial edema, erythema multiforme, hallucinations (auditory and visual), hemolytic uremic syndrome (HUS), hepatitis, hypertension, leukocytoclastic vasculitis, mania, photosensitivity reaction, psychosis, rash, renal failure, seizure, tachycardia, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome, tremor, visual disturbances

Cimetidine: Decreased renal clearance of acyclovir; no dosage adjustment needed in patients with normal renal function

Probenecid: Decreased renal clearance of acyclovir; no dosage adjustment needed in patients with normal renal function

Absorption: Rapid

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

Protein binding: 13.5% to 17.9%

Metabolism: Hepatic; valacyclovir is rapidly and nearly completely converted to acyclovir and L-valine by first-pass effect; acyclovir is hepatically metabolized to a very small extent by aldehyde oxidase and by alcohol and aldehyde dehydrogenase (inactive metabolites)

Bioavailability: ~55% once converted to acyclovir

Half-life elimination: Normal renal function: Adults: Acyclovir: 2.5-3.3 hours, Valacyclovir: ~30 minutes; End-stage renal disease: Acyclovir: 14-20 hours

Excretion: Urine, primarily as acyclovir (88%); Note: Following oral administration of radiolabeled valacyclovir, 46% of the label is eliminated in the feces (corresponding to nonabsorbed drug), while 47% of the radiolabel is eliminated in the urine.

Adolescents and Adults: Herpes labialis (cold sores): 2 g twice daily for 1 day (separate doses by ~12 hours)

Adults:

Herpes zoster (shingles): 1 g 3 times/day for 7 days

Genital herpes:

Initial episode: 1 g twice daily for 10 days

Recurrent episode: 500 mg twice daily for 3 days

Reduction of transmission: 500 mg once daily (source partner)

Suppressive therapy:

Immunocompetent patients: 1000 mg once daily (500 mg once daily in patients with <9 recurrences per year)

HIV-infected patients (CD4 100 cells/mm³): 500 mg twice daily

Dosing interval in renal impairment:

Herpes zoster: Adults:

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

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

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

Genital herpes: Adults:

Initial episode:

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

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

Recurrent episode: Clcr<10-29 mL/minute: 500 mg every 24 hours

Suppressive therapy: Clcr<10-29 mL/minute:

For usual dose of 1 g every 24 hours, decrease dose to 500 mg every 24 hours

For usual dose of 500 mg every 24 hours, decrease dose to 500 mg every 48 hours

HIV-infected patients: 500 mg every 24 hours

Herpes labialis: Adolescents and Adults:

Clcr 30-49 mL/minute: 1 g every 12 hours for 2 doses

Clcr 10-29 mL/minute: 500 mg every 12 hours for 2 doses

Clcr<10 mL/minute: 500 mg as a single dose

Hemodialysis: Dialyzable (~33% removed during 4-hour session); administer dose postdialysis

Chronic ambulatory peritoneal dialysis/continuous arteriovenous hemofiltration dialysis: Pharmacokinetic parameters are similar to those in patients with ESRD; supplemental dose not needed following dialysis

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.