Valacyclovir

Indications

Valacyclovir is used for: Genital herpes, Herpes zoster, Herpes labialis, CMV infections

Adult Dose

Oral Herpes zoster (shingles) Adult: 1 g tid for 7 days. Immunocompromised patients: Continue treatment for a further 2 days after crusting of lesions. Herpes simplex infections of skin and mucous membranes; Genital herpes Adult: 500 mg bid for 3-5 days for recurrent episodes or up to 10 days for initial episodes. Immunocompromised patients: 1 g bid for at least 5 days for recurrent episodes or up to 10 days for initial episodes. Prophylaxis of cytomegaloviral infections in immunocompromised patients Adult: 2 g 4 times daily, begin as soon as possible post-transplant and usually continued for 90 days. Herpes labialis Adult: 2 g 12 hrly for 1 day. Suppression of recurrent herpes simplex Adult: 500 mg daily as a single or in 2 divided doses. Immunocompromised patients: 500 mg bid. Treatment is re-evaluated after 6-12 mth of therapy.

Child Dose

Herpes simplex infections of skin and mucous membranes; Genital herpes Child: >12 yr: 500 mg bid for 3-5 days for recurrent episodes or up to 10 days for initial episodes. Immunocompromised patients: 1 g bid for at least 5 days for recurrent episodes or up to 10 days for initial episodes. Prophylaxis of cytomegaloviral infections in immunocompromised patients Child: >12 yr: 2 g 4 times daily, begin as soon as possible post-transplant and usually continued for 90 days. Herpes labialis Child: >12 yr: 2 g 12 hrly for 1 day. Suppression of recurrent herpes simplex Adult: Child: >12 yr: 500 mg daily as a single or in 2 divided doses. Immunocompromised patients: 500 mg bid. Treatment is re-evaluated after 6-12 mth of therapy. Chickenpox <2 years: Safety and efficacy not established >2 years: 20 mg/kg PO q8hr for 5 days; not to exceed 1 g PO q8hr

Renal Dose

Herpes labialis CrCl 30-49 mL/min: 1 g PO q12hr for 1 day CrCl 10-29 mL/min: 500 mg PO q12hr for 1 day CrCl <10 mL/min: 500 mg PO once Herpes zoster CrCl 30-49 mL/min: 1 g PO q12hr CrCl 10-29 mL/min: 1 g/day PO CrCl <10 mL/min: 500 mg/day PO Genital herpes (initial episode) CrCl 10-29 mL/min: 1 g/day PO CrCl <10 mL/min: 500 mg/day PO qDay Genital herpes (recurrent episodes)(suppressive therapy, immunocompetent patients) CrCl <29 mL/min: 500 mg/day PO

Administration

May be taken with or without food. May be taken w/ meals to reduce GI discomfort.

Contra Indications

Hypersensitvity to valaciclovir, aciclovir.

Precautions

Patient at risk of dehydration. Renal impairment. Pregnancy and lactation. Patient Counselling Avoid sexual intercourse when symptoms of genital herpes are present. Monitoring Parameters Monitor renal, hepatic and haematological functions. Lactation: Drug excreted in breast milk; use with caution

Pregnancy-Lactation

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

Interactions

Increased risk of renal failure w/ nephrotoxic drugs (e.g. aminoglycosides, organoplatinum compounds, iodinated contrast media, methotrexate, pentamidine, foscarnet, ciclosporin, tacrolimus). Probenecid and cimetidine may increase peak plasma concentrations and AUC of aciclovir.

Adverse Effects

Side effects of Valacyclovir : >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 Potentially Fatal: Hepatitis; renal failure; blood dyscrasias; thrombotic thrombocytopenic purpura-hemolytic uremic syndrome.

Mechanism of Action

Valaciclovir is the L-valine ester of aciclovir. A prodrug, it is rapidly converted to aciclovir by intestinal and hepatic metabolism. Aciclovir inhibits DNA synthesis and viral replication and has antiviral activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) and varicella-zoster virus.