Valaciclovir

Valaciclovir is the L-valyl ester prodrug of acyclovir, with oral bioavailability of about 55% and a simpler dosing schedule. It is the usual oral drug for genital herpes, herpes labialis and zoster, and is used for cytomegalovirus prophylaxis in kidney transplantation. It shares the neurotoxicity and kidney risks of acyclovir, and thrombotic microangiopathy has been reported at high doses in advanced HIV and transplantation.

Class. Nucleoside analogue antiviral; prodrug.

Mechanism. Hydrolysed to acyclovir, which is phosphorylated by viral thymidine kinase and inhibits viral DNA polymerase with chain termination.

Pharmacokinetics. Rapid conversion to acyclovir, absorption not affected by food, half life of acyclovir about 3 hours, renal excretion.

Genital herpes. - First episode: 1 g orally twice daily for 7 to 10 days. - Recurrent episode: 500 mg twice daily for 3 days (or 1 g once daily for 5 days). - Suppression: 500 mg once daily (1 g once daily if more than 10 episodes a year); in HIV infection 500 mg twice daily.

Herpes labialis. 2 g twice daily for 1 day, 12 hours apart.

Herpes zoster. 1 g three times daily for 7 days, started within 72 hours of the rash.

Cytomegalovirus prophylaxis (kidney transplant). 2 g four times daily for up to 90 days, with dose reduction for kidney function.

Children. Aged 12 years and over: adult dosing; younger children: weight-based, unlicensed in many settings.

Maximum: 8 g daily. Loading dose: none. Titration: by kidney function.

Contraindications. Hypersensitivity to valaciclovir or acyclovir.

Serious adverse effects. Acute kidney injury, thrombotic thrombocytopenic purpura or haemolytic uraemic syndrome (advanced HIV, transplantation, high dose), confusion, hallucinations and seizures (particularly in kidney impairment).

Common adverse effects. Headache, nausea, abdominal pain and dizziness.

Interactions. Probenecid and cimetidine raise acyclovir levels; mycophenolate levels rise; nephrotoxic drugs add risk.

Common prescribing errors. Not reducing the dose in kidney impairment, using high doses for CMV prophylaxis without monitoring, and treating late (after 72 hours).

Special groups. - Pregnancy: used when indicated; late-pregnancy suppression from 36 weeks lowers recurrence at delivery. - Breastfeeding: compatible. - Children: from 12 years (adult dose). - Older adults: reduced clearance; adjust for kidney function. - Kidney impairment: zoster: CrCl 30 to 49 mL/min 1 g every 12 hours; 10 to 29: 1 g every 24 hours; under 10: 500 mg every 24 hours. Genital herpes: CrCl under 30: lengthen interval, with 500 mg every 24 hours for suppression. - Liver impairment: no adjustment.

Formulations. Tablets 500 mg and 1 g.

Administration. With or without food and ample fluid.

Baseline. Creatinine, weight, HIV status and pregnancy status.

Monitoring. Creatinine on high-dose or prolonged use; neurological symptoms; full blood count in advanced HIV or transplantation.

Stopping thresholds. Stop for neurotoxicity, thrombotic microangiopathy or kidney injury.

Referral and escalation. Specialist review for ophthalmic zoster, immunocompromise, suspected resistance or neurological symptoms.