VALTREX
Clinical safety rating: caution
Comprehensive clinical and safety monograph for VALTREX (VALTREX).
Valacyclovir, a prodrug of acyclovir, is phosphorylated intracellularly to acyclovir triphosphate, which competitively inhibits viral DNA polymerase and incorporates into viral DNA, causing chain termination.
| Metabolism | Valacyclovir is rapidly converted to acyclovir by first-pass intestinal and hepatic metabolism via valacyclovir hydrolase. Acyclovir is partially metabolized by aldehyde oxidase and alcohol dehydrogenase, with minor oxidation products. |
| Excretion | Renal elimination: >90% as valacyclovir metabolites (primarily acyclovir, 9-carboxymethoxymethylguanine, and 8-hydroxy-9-carboxymethoxymethylguanine) via active tubular secretion and glomerular filtration. Fecal excretion: <5%. |
| Half-life | Terminal elimination half-life of acyclovir (active metabolite) is 2.5–3.3 hours in adults with normal renal function; prolonged to 14 hours in end-stage renal disease. |
| Protein binding | Acyclovir: 9–33% (concentration-dependent, saturable); valacyclovir: minimal (~15%). Primarily binds to albumin. |
| Volume of Distribution | Acyclovir: 0.7–1.2 L/kg (apparent Vd), indicating distribution into total body water and intracellular compartments. |
| Bioavailability | Oral valacyclovir: ~54% (converted to acyclovir); absorption enhanced by food (bioavailability not significantly altered). Acyclovir oral bioavailability is ~10–20%; valacyclovir is a prodrug to improve absorption. |
| Onset of Action | Oral: clinical effect (symptom relief) for herpes labialis occurs within 24–48 hours; for herpes zoster, symptom improvement begins within 2–3 days. Peak plasma concentrations reached 1–2 hours after oral administration. |
| Duration of Action | Dosing interval of 8–12 hours for most indications (e.g., herpes zoster, genital herpes) due to rapid elimination; duration of clinical effect supports thrice-daily dosing. In immunocompromised patients, extended intervals may be needed with renal impairment. |
For herpes zoster: 1 g orally three times daily for 7 days. For genital herpes initial episode: 1 g orally twice daily for 10 days. For recurrent genital herpes: 500 mg orally twice daily for 3 days. For herpes labialis: 2 g orally twice daily for 1 day. For varicella: 20 mg/kg orally three times daily for 5 days (max 1 g three times daily).
| Dosage form | Tablet |
| Renal impairment | CrCl 30-49 mL/min: same dose as normal but interval every 12 hours. CrCl 10-29 mL/min: same dose every 24 hours. CrCl <10 mL/min: 50% of dose every 24 hours. For hemodialysis: administer dose post-dialysis. |
| Liver impairment | No dosage adjustment required for Child-Pugh Class A or B. For Child-Pugh Class C: reduce dose by 50% and consider extending dosing interval. |
| Pediatric use | For varicella (≥2 years): 20 mg/kg orally three times daily for 5 days (max 1 g three times daily). For herpes labialis (≥12 years): 2 g orally twice daily for 1 day. For genital herpes (≥12 years): same dosing as adults. For neonates (up to 3 months): 20 mg/kg orally three times daily. For children <2 years: not established for all indications. |
| Geriatric use | Due to age-related renal impairment, base dosing on creatinine clearance; consider monitoring renal function and adjusting dose accordingly. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for VALTREX (VALTREX).
| Breastfeeding | Valacyclovir is excreted into human breast milk. The milk-to-plasma (M/P) ratio is approximately 1.3 for acyclovir (the active metabolite). The estimated infant dose via breast milk is about 1-2% of the maternal therapeutic dose. The American Academy of Pediatrics considers valacyclovir compatible with breastfeeding. Monitor infant for rash or diarrhea. |
| Teratogenic Risk | Valacyclovir is classified as FDA Pregnancy Category B. Animal studies have not demonstrated teratogenicity or fetotoxicity. There are no adequate and well-controlled studies in pregnant women. However, data from the Valacyclovir Pregnancy Registry and observational studies suggest no increased risk of major birth defects compared to the general population. Risk cannot be ruled out; use only if clearly needed. |
■ FDA Black Box Warning
Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), including fatal cases, have occurred in immunocompromised patients receiving high doses.
| Serious Effects |
Hypersensitivity to valacyclovir, acyclovir, or any component of the formulation.
| Precautions | Renal impairment (dosage adjustment required), central nervous system effects (agitation, hallucinations, confusion, encephalopathy), thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS, especially in immunocompromised high-dose patients), fetal/neonatal risk (use only if benefit outweighs risk), geriatric use (higher risk of CNS effects and renal dysfunction). |
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| Fetal Monitoring | No specific maternal or fetal monitoring required beyond standard prenatal care. For women treated during pregnancy for herpes simplex or varicella-zoster, monitor for maternal adverse effects (e.g., renal function, CNS effects) and fetal growth via routine ultrasound if indicated. |
| Fertility Effects | No known adverse effects on fertility in animal studies. There are no human data on fertility impact. The drug does not affect spermatogenesis or oogenesis in preclinical studies. |