valacyclovir (Rx)

>10%

Headache (14-35%)

Neutropenia (<18%)

Elevated aspartate transaminase (AST) (2-16%)

Nasopharyngitis (<16%)

Nausea (6-15%)

Elevated alanine transaminase (ALT) (<14%)

Abdominal pain (2-11%)

1-10%

Dysmenorrhea (1-8%)

Depression (<7%)

Arthralgia (<1-6%)

Vomiting (<1-6%)

Dizziness (2-4%)

Rash (≤8%)

Rhinorrhea (<2%)

Thrombocytopenia (<3%)

Leukopenia (≤1%)

<1%

Agitation

Aggression

Alopecia

Confusion

Erythema multiforme

Hypertension

Tachycardia

Tremor

Visual disturbances

Contraindications

Hypersensitivity to valacyclovir or acyclovir

Cautions

Thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (HUS) reported in patients with advanced HIV disease and in allogenic bone marrow transplant and renal transplant recipients

Acute renal failure (ARF) may occur, especially in elderly patients or those with underlying renal impairment receiving higher than recommended doses; use with caution in patients with renal impairment, the elderly, and/or patients receiving nephrotoxic drugs

Treatment should begin with the earliest symptom (tingling, burning, itching) in cold sores; for genital herpes, it should begin at the first signs and symptoms (within 72 hours of onset of first diagnosis or 24 hours of onset of recurrent episodes); for herpes zoster, it should begin within 72 hours of onset of rash; for chicken pox, it should begin with the earliest sign or symptom

Central nervous system (CNS) effects may occur (eg, agitation, hallucinations, confusion, encephalopathy); risk of CNS adverse effects is higher in elderly patients

Adequately hydrate patient; decreased precipitation in renal tubules may occur

Pregnancy

Clinical data over several decades with valacyclovir and its metabolite, acyclovir, in pregnant women, have not identified a drug associated risk of major birth defects; there are insufficient data on use of valacyclovir regarding miscarriage or adverse maternal or fetal outcomes; there are risks to fetus associated with untreated herpes simplex during pregnancy

Risk of neonatal HSV infection varies from 30% to 50% for genital HSV acquired in late pregnancy (third trimester), whereas with HSV acquisition in early pregnancy, risk of neonatal infection is about 1%; a primary herpes occurrence during first trimester of pregnancy has been associated with neonatal chorioretinitis, microcephaly, and, in rare cases, skin lesions; in very rare cases, transplacental transmission can occur resulting in congenital infection, including microcephaly, hepatosplenomegaly, intrauterine growth restriction, and stillbirth

Co-infection with HSV increases risk of perinatal HIV transmission in women who had a clinical diagnosis of genital herpes during pregnancy

Animal data

• In animal reproduction studies, no evidence of adverse developmental outcomes was observed with valacyclovir when administered to pregnant rats and rabbits at system exposures (AUC) 4 (rats) and 7 (rabbits) times human exposure at maximum recommended human dose (MRHD)

Lactation

Although there is no information on presence of drug in human milk, its metabolite, acyclovir, is present in human milk following oral administration of drug; based on published data, a 500-mg maternal dose twice daily would provide a breastfed child with an oral acyclovir dosage of approximately 0.6 mg/kg/day; there is no data on effects of drug on breastfed child or on milk production

Consider developmental and health benefits of breastfeeding along with mother’s clinical need for therapy and any potential adverse effects on breastfed child from drug or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Converted to acyclovir by intestinal and hepatic metabolism

Competes with deoxyguanosine triphosphate for viral DNA polymerase to inhibit DNA synthesis and viral replication

Absorption

Rapidly absorbed

Bioavailability: ~55% (after conversion to acyclovir)

Distribution

Acyclovir (active drug) is widely distributed throughout the body, including brain, kidney, muscle, uterus, lungs, liver, spleen, vagina, and cerebrospoinal fluid (CSF)

Protein bound: 13.5-17.9%

Metabolism

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

Elimination

Half-life (normal renal function, adults): Acyclovir, 2.5-3.3 hr; valacyclovir, ~30 min

Half-life (end-stage renal disease): Acyclovir, 14-20 hr

Excretion: Urine (89%), feces (minimal)