Valacyclovir is a prodrug of acyclovir.
Valacyclovir has activity against herpesviruses.
Valacyclovir is converted to acyclovir, which is converted to its triphosphate form, acyclovir triphosphate (ACV-TP). ACV-TP competitively inhibits viral DNA polymerase, incorporates into and terminates the growing viral DNA chain, and inactivates of the viral DNA polymerase.
The primary mechanism of resistance to valacyclovir is related to viral thymidine kinase and DNA polymerase mutations.
No relationship has been established between the effective in vitro and in vivo concentrations of valacyclovir.
Valacyclovir is well absorbed via intestinal brush border membranes and undergoes rapid and extensive first-pass intestinal/hepatic metabolism by the enzyme valacyclovir hydrolase to acyclovir and L-valine.
Adverse effects include nausea, headache, vomiting, dizziness and abdominal pain.
Oral: 500mg and 1g caplet
HSV infections of skin and mucous membranes including initial and recurrent genital herpes
Adult: Initial genital: 1 g po bid for 7 – 10 days
Recurrent genital: 500 mg bid for 3 – 5 days or 1 g po qd x 5 days
Pediatric: Safety and efficacy in pre-pubertal pediatric patients not established.
Episodic HSV treatment in HIV-infected patients
Adult: 1 g po bid x 5 – 10 days
Pediatric: No data
Suppression of recurrent HSV in immunocompetent patients
Adult: 1 g qd or
500 mg qd if ≤ 9 recurrences per year
Pediatric: No data
Prophylaxis of HSV in immunocompromised patients
Adult: 500 mg bid
Pediatric: No data
Herpes labialis (cold sores)
Adult: 2 g bid for 1 day taken 12 hours apart (initiate at earliest symptom of cold sore i.e. tingling, itching, burning)
Recurrent orolabial infection in HIV-infected patients: 500 mg bid
Pediatric: No data
VZV infections including varicella (chicken pox) and herpes zoster (shingles)
Adult: 1 g po q8h x 7 days
Pediatric: No data
Renal Impairment: Herpes Zoster: CrCl 30 to 49ml/min give 1000mg PO q12h
CrCl 10 to 29ml/min give 1000mg PO q24h
CrCl <10ml/min give 500mg PO q24h
Genital herpes: CrCl 10 to 29ml/min give 1000mg PO q24h
CrCl <10ml/min give 500mg PO q24h
Suppressive therapy: CrCl <29ml/min give 500mg PO q24h
Cold sores: CrCl 30 to 49ml/min give 1000mg PO q12h x 2 doses
CrCl 10 to 29ml/min give 500mg PO q12h x 2 doses
CrCl <10ml/min give 500mg PO x 1 dose
Hepatic Impairment: No dosage adjustment necessary in hepatic insufficiency
Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), in some cases resulting in death, has occurred in patients with advanced HIV disease and also in allogeneic bone marrow transplant and renal transplant recipients participating in clinical trials of valacyclovir at doses of 8 grams per day.
Use caution when combining valacyclovir with potentially nephrotoxic agents.
Category B: No evidence of risk in humans but studies inadequate.
Baseline serum creatinine/BUN
Valtrex®/Glaxo Smithkline