Drug reference

Valacyclovir

Antiviral

Also known as Valacyclovir hydrochloride, Valtrex

AntiviralATC J05AB11

CDSCO approvedSchedule HJan AushadhiATC J05AB11

EXCRETION

—

not curated

INTERACTIONS

—

none in our sources

PREGNANCY

Pregnancy Category B (FDA). Animal studies show no evidence of fetal harm, but human studies are limited. Use in pregnancy is generally considered acceptable when clinically indicated, especially for severe or disseminated infections.

FDA category + note

Mechanism

Valacyclovir is a prodrug that is rapidly converted to acyclovir, which is a synthetic purine nucleoside analogue. Acyclovir is phosphorylated to its active triphosphate form by viral thymidine kinase, primarily inhibiting viral DNA polymerase. This action prevents viral DNA replication, effectively stopping the spread of herpes viruses.

Indications

Herpes zoster (shingles)Genital herpes (treatment of initial and recurrent episodes)Suppression of recurrent genital herpesHerpes labialis (cold sores)Varicella (chickenpox) in immunocompetent adolescents and adultsPrevention of cytomegalovirus (CMV) disease following organ transplantation (off-label)initial genital HSV infectionsrecurrent genital HSV episodessuppression of frequently recurring genital herpesrecurrent orolabial herpesherpes zosterherpes simplex keratitis (off-label)herpes zoster ophthalmicusgenital herpes simplex (first episode)genital herpes simplex (recurrent episode)genital herpes simplex (suppressive treatment)genital herpes simplexorolabial herpesherpes zoster (drug of choice)Genital herpes (primary and recurrent episodes)Orolabial herpes (primary and recurrent episodes)Suppressive therapy for genital herpesVaricellaZoster

Dosing

Adult: Herpes Zoster: 1000 mg orally three times daily for 7 days. Genital Herpes (initial episode): 1000 mg orally twice daily for 7-10 days. Genital Herpes (recurrent episode): 500 mg orally twice daily for 3 days. Genital Herpes (suppression): 500 mg orally once daily (or 1000 mg once daily for very frequent recurrences). Herpes Labialis: 2000 mg orally twice daily for 1 day, taken 12 hours apart.
Pediatric: Herpes Labialis (≥12 years): 2000 mg orally twice daily for 1 day, taken 12 hours apart. Chickenpox (2-18 years): 20 mg/kg orally three times daily for 5 days (maximum 1000 mg per dose).
Renal adjustment: Creatinine clearance (CrCl) 30-49 mL/min: Reduce dose by approximately 50%. CrCl 10-29 mL/min: Further reduction (e.g., 1000 mg every 24 hours for zoster). CrCl <10 mL/min or on hemodialysis: Significant reduction (e.g., 500 mg every 24-48 hours for zoster, administered after dialysis).
Hepatic adjustment: No dosage adjustment is required for mild to moderate hepatic impairment. Use with caution in severe hepatic impairment as pharmacokinetic data are limited.
Geriatric: Dose adjustment is required based on renal function, as elderly patients are more likely to have impaired renal function. Adequate hydration should be maintained.
Max dose: Varies by indication. For Herpes Zoster, typically 3000 mg/day. For Herpes Labialis, 4000 mg/day (for 1 day).

Pharmacokinetics

Onset

Rapid conversion to acyclovir occurs after oral administration.

Peak effect

Acyclovir: 1-2 hours after valacyclovir administration.

Duration

Intracellular half-life of acyclovir triphosphate is significantly longer than plasma half-life, allowing for less frequent dosing.

Half-life

Acyclovir: 2.5-3.3 hours (in individuals with normal renal function).

Bioavailability

54% (of acyclovir after valacyclovir administration, which is ~3-5 times higher than oral acyclovir)

Protein binding

Acyclovir: 13.5-16%.

Metabolism

Rapidly and almost completely converted to acyclovir and L-valine by first-pass intestinal and hepatic metabolism via the enzyme valacyclovir hydrolase. Acyclovir is minimally metabolized.

Excretion

Primarily renal excretion (80-90% as acyclovir, <1% as valacyclovir in urine).

Contraindications

Hypersensitivity to valacyclovir, acyclovir, or any component of the formulation.
Known history of thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) in severely immunocompromised patients.

Side effects

Common

HeadacheNauseaAbdominal painFatigueDizzinessDiarrhea

Serious

Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS) (rare, primarily in severely immunocompromised patients)
Acute renal failure
Encephalopathy
Seizures
Angioedema
Hallucinations
nephrotoxicity
CNS symptoms (confusion, hallucinations)
severe thrombocytopenic syndromes (uncommon, immunocompromised patients)
thrombotic thrombocytopenic purpura (at 4 g/d in HIV-infected persons)

Pregnancy & lactation

Pregnancy

Lactation

Acyclovir (the active metabolite of valacyclovir) is excreted into breast milk. Limited data suggest low levels in milk and minimal infant exposure. Generally considered compatible with breastfeeding, but caution is advised, and physician consultation is recommended.