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Pronunciation
(val ay SYE kloe veer)
Generic Available (U.S.)
Yes
Index Terms
Brand Names: U.S.
Brand Names: Canada
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Treatment of herpes zoster (shingles) in immunocompetent patients; treatment of first-episode and recurrent genital herpes; suppression of recurrent genital herpes and reduction of heterosexual transmission of genital herpes in immunocompetent patients; suppression of genital herpes in HIV-infected individuals; treatment of herpes labialis (cold sores); chickenpox in immunocompetent children
Use: Dental
Treatment of herpes labialis (cold sores)
Use: Unlabeled/Investigational
Prophylaxis of cancer-related HSV, VZV, and CMV infections; treatment of cancer-related HSV, VZV infection
Pregnancy Risk Factor
B
Pregnancy Considerations
Teratogenic events were not observed in animal studies. Data from a pregnancy registry has shown no increased rate of birth defects than that of the general population; however, the registry is small and use during pregnancy is only warranted if the potential benefit to the mother justifies the risk of the fetus.
Lactation
Enters breast milk/use caution
Breast-Feeding Considerations
Peak concentrations in breast milk range from 0.5-2.3 times the corresponding maternal acyclovir serum concentration. This is expected to provide a nursing infant with a dose of acyclovir equivalent to ~0.6 mg/kg/day following ingestion of valacyclovir 500 mg twice daily by the mother. Use with caution while breast-feeding.
Contraindications
Hypersensitivity to valacyclovir, acyclovir, or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• CNS effects: CNS adverse effects (including agitation, hallucinations, confusion, delirium, seizures, and encephalopathy) have been reported in both adult and pediatric patients with or without renal dysfunction. Elderly patients are more likely to experience CNS adverse effects.
• Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome: Has occurred in immunocompromised patients (at doses of 8 g/day).
• Urinary precipitation: Decreased precipitation in renal tubules may occur; adequately hydrate patient.
Disease-related concerns:
• Renal impairment: Use caution in patients with renal impairment, the elderly, and/or those receiving nephrotoxic agents. Acute renal failure and CNS effects have been observed in patients with renal dysfunction; dose adjustment may be required. Precipitation in renal tubules may occur; maintain adequate hydration.
Special populations:
• Elderly: Use with caution in the elderly; CNS effects have been reported.
• Immunocompromised patients: Advanced HIV (CD4 <100 cells/mm3): Safety and efficacy have not been established for treatment/suppression of recurrent genital herpes or disseminated herpes in patients with profound immunosuppression.
• Pediatrics: Safety and efficacy have not been established in patients <2 years of age.
Other warnings/precautions:
• Appropriate use: For cold sores, treatment should begin with earliest symptom (tingling, itching, burning). For genital herpes, treatment should begin as soon as possible after the first signs and symptoms (within 72 hours of onset of first diagnosis or within 24 hours of onset of recurrent episodes). For herpes zoster, treatment should begin within 72 hours of onset of rash. For chickenpox, treatment should begin with earliest sign or symptom.
Adverse Reactions
>10%:
Central nervous system: Headache (13% to 38%)
Gastrointestinal: Nausea (5% to 15%), abdominal pain (1% to 11%)
Hematologic: Neutropenia (≤18%)
Hepatic: ALT increased (≤14%), AST increased (2% to 16%)
Respiratory: Nasopharyngitis (≤16%)
1% to 10%:
Central nervous system: Fatigue (≤8%), depression (≤7%), fever (children 4%), dizziness (2% to 4%)
Dermatologic: Rash (≤8%)
Endocrine: Dysmenorrhea (≤1% to 8%), dehydration (children 2%)
Gastrointestinal: Vomiting (<1% to 6%), diarrhea (children 5%; adults <1%)
Hematologic: Thrombocytopenia (≤3%)
Hepatic: Alkaline phosphatase increased (≤4%)
Neuromuscular & skeletal: Arthralgia (<1 to 6%)
Respiratory: Rhinorrhea (children 2%)
Miscellaneous: Herpes simplex (children 2%)
<1%, postmarketing, and/or case reports: Acute hypersensitivity reactions (angioedema, anaphylaxis, dyspnea, pruritus, rash, urticaria); aggression, agitation, alopecia, anemia, aplastic anemia, ataxia, creatinine increased, coma, confusion, consciousness decreased, delirium, dysarthria, encephalopathy, erythema multiforme, facial edema, hallucinations (auditory and visual), hemolytic uremic syndrome (HUS), hepatitis, hypertension, leukocytoclastic vasculitis, leukopenia, mania, photosensitivity reaction, psychosis, renal failure, renal pain, seizure, tachycardia, thrombotic thrombocytopenic purpura (TTP), tremor, urinary precipitation, visual disturbances
Metabolism/Transport Effects
None known.
Drug Interactions
Mycophenolate: May increase the serum concentration of Acyclovir-Valacyclovir. Acyclovir-Valacyclovir may increase the serum concentration of Mycophenolate. Risk C: Monitor therapy
Tenofovir: Acyclovir-Valacyclovir may decrease the excretion of Tenofovir. Risk C: Monitor therapy
Zidovudine: Acyclovir-Valacyclovir may enhance the CNS depressant effect of Zidovudine. Risk C: Monitor therapy
Zoster Vaccine: Acyclovir-Valacyclovir may diminish the therapeutic effect of Zoster Vaccine. Management: When possible, discontinue antiviral agents with anti-zoster activity (i.e., acyclovir, valacyclovir, famciclovir) for at least 24 hours prior to and 14 days after receiving a live attenuated zoster vaccine. Risk X: Avoid combination
Storage
Store at 15°C to 25°C (59°F to 77°F).
Mechanism of Action
Valacyclovir is rapidly and nearly completely converted to acyclovir by intestinal and hepatic metabolism. Acyclovir is converted to acyclovir monophosphate by virus-specific thymidine kinase then further converted to acyclovir triphosphate by other cellular enzymes. Acyclovir triphosphate inhibits DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase and being incorporated into viral DNA.
Pharmacodynamics/Kinetics
Absorption: Rapid
Distribution: Acyclovir is widely distributed throughout the body including brain, kidney, lungs, liver, spleen, muscle, uterus, vagina, and CSF
Protein binding: ~14% to 18%
Metabolism: Hepatic; valacyclovir is rapidly and nearly completely converted to acyclovir and L-valine by first-pass effect; acyclovir is hepatically metabolized to a very small extent by aldehyde oxidase and by alcohol and aldehyde dehydrogenase (inactive metabolites)
Bioavailability: ~55% once converted to acyclovir
Half-life elimination: Normal renal function: Adults: Acyclovir: 2.5-3.3 hours, Valacyclovir: ~30 minutes; End-stage renal disease: Acyclovir: 14-20 hours; During hemodialysis: 4 hours
Excretion: Urine, primarily as acyclovir (89%); Note: Following oral administration of radiolabeled valacyclovir, 46% of the label is eliminated in the feces (corresponding to nonabsorbed drug), while 47% of the radiolabel is eliminated in the urine.
Dosage
Oral:
Children 2 to <18 years: Chickenpox: 20 mg/kg/dose 3 times/day for 5 days (maximum: 1 g 3 times/day)
Children ≥12 and Adults: Herpes labialis (cold sores): 2 g twice daily for 1 day (separate doses by ~12 hours)
Adults:
CMV prophylaxis in allogeneic HSCT recipients (unlabeled use): 2 g 4 times/day
Herpes zoster (shingles): 1 g 3 times/day for 7 days
HSV, VZV in cancer patients (unlabeled use): Prophylaxis: 500 mg 2-3 times/day; Treatment: 1 g 3 times/day
Genital herpes:
Initial episode: 1 g twice daily for 10 days
Recurrent episode: 500 mg twice daily for 3 days
Reduction of transmission: 500 mg once daily (source partner)
Suppressive therapy:
Immunocompetent patients: 1000 mg once daily (500 mg once daily in patients with <9 recurrences per year)
HIV-infected patients (CD4 ≥100 cells/mm3): 500 mg twice daily
Dosing adjustment in renal impairment:
Herpes zoster: Adults:
Clcr 30-49 mL/minute: 1 g every 12 hours
Clcr 10-29 mL/minute: 1 g every 24 hours
Clcr <10 mL/minute: 500 mg every 24 hours
Genital herpes: Adults:
Initial episode:
Clcr 10-29 mL/minute: 1 g every 24 hours
Clcr <10 mL/minute: 500 mg every 24 hours
Recurrent episode: Clcr <29 mL/minute: 500 mg every 24 hours
Suppressive therapy: Clcr <29 mL/minute:
For usual dose of 1 g every 24 hours, decrease dose to 500 mg every 24 hours
For usual dose of 500 mg every 24 hours, decrease dose to 500 mg every 48 hours
HIV-infected patients: 500 mg every 24 hours
Herpes labialis: Adolescents and Adults:
Clcr 30-49 mL/minute: 1 g every 12 hours for 2 doses
Clcr 10-29 mL/minute: 500 mg every 12 hours for 2 doses
Clcr <10 mL/minute: 500 mg as a single dose
Hemodialysis: Dialyzable (~33% removed during 4-hour session); administer dose postdialysis
Chronic ambulatory peritoneal dialysis/continuous arteriovenous hemofiltration dialysis: Pharmacokinetic parameters are similar to those in patients with ESRD; supplemental dose not needed following dialysis
Dosing adjustment in hepatic impairment: No adjustment required.
Dental Usual Dosing
Herpes labialis (cold sores): Adolescents and Adults: Oral: 2 g twice daily for 1 day (separate doses by ~12 hours)
Administration: Oral
If GI upset occurs, administer with meals.
Monitoring Parameters
Urinalysis, BUN, serum creatinine, liver enzymes, and CBC
Dietary Considerations
May be taken with or without food.
Patient Education
This medication is not a cure for genital herpes; it is not known if it will prevent transmission to others. Use appropriate precautions to prevent spread to other persons. Begin use at first sign of herpes. Maintain adequate hydration, unless instructed to restrict fluid intake. May cause headache, dizziness, nausea, vomiting, or abdominal pain. Immediately report difficulty swallowing or breathing, rash, or hives.
Geriatric Considerations
More convenient dosing and increased bioavailability, without increasing side effects, make valacyclovir a favorable choice compared to acyclovir. Has been shown to accelerate resolution of postherpetic pain. Adjust dose for renal impairment.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause aggression, agitation, confusion, encephalopathy, hallucinations, mania, psychosis
Mental Health: Effects on Psychiatric Treatment
Use caution in patients with renal impairment; CNS symptoms have been reported in these patients
Nursing: Physical Assessment/Monitoring
Monitor for CNS changes (dizziness, depression), nausea, vomiting, dysmenorrhea, and arthralgia. Teach patient appropriate timing of treatment.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Caplet, oral: 500 mg, 1 g
Valtrex®: 500 mg
Valtrex®: 1 g [scored]
Tablet, oral: 500 mg, 1 g
Pricing: U.S. (www.drugstore.com)
Tablets (Valacyclovir HCl)
1 g (30): $340.99
500 mg (30): $185.99
Tablets (Valtrex)
1 g (30): $365.87
500 mg (30): $235.98
Extemporaneously Prepared
A 50 mg/mL oral suspension may be made with caplets and either Ora-Sweet® or Ora-Sweet SF®. Crush eighteen 500 mg caplets in a mortar and reduce to a fine powder. Add 5 mL portions of chosen vehicle (40 mL total) and mix to a uniform paste; transfer to a 180 mL calibrated amber glass bottle, rinse mortar with 10 mL of vehicle 5 times, and add quantity of vehicle sufficient to make 180 mL. Label "shake well" and "refrigerate". Stable for 21 days refrigerated.
Fish DN, Vidaurri VA, and Deeter RG, "Stability of Valacyclovir Hydrochloride in Extemporaneously Prepared Oral Liquids," Am J Health Syst Pharm, 1999, 56(19):1957-60.
References
Acosta EP and Fletcher CV, “Valacyclovir,” Ann Pharmacother, 1997, 31(2):185-91.
Alrabiah FA and Sacks SL, “New Antiherpesvirus Agents. Their Targets and Therapeutic Potential,” Drugs, 1996, 52(1):17-32.
Beutner KR, Friedman DJ, Forszpaniak C, et al, “Valacyclovir Compared With Acyclovir for Improved Therapy for Herpes Zoster in Immunocompetent Adults,” Antimicrob Agents Chemother, 1995, 39(7):1546-53.
Bodsworth NJ, Crooks RJ, Borelli S, et al, “Valaciclovir Versus Aciclovir in Patients Initiated Treatment of Recurrent Genital Herpes: A Randomized, Double-Blind Clinical Trial. International Valaciclovir HSV Study Group,” Genitourin Med, 1997, 73(2):110-6.
Centers for Disease Control and Prevention (CDC), "Sexually Transmitted Diseases Treatment Guidelines, 2010," MMWR Recomm Rep, 2010, 59(RR-12):1-110.
Grant DM, Mauskopf JA, Bell L, et al, “Comparison of Valaciclovir and Acyclovir for the Treatment of Herpes Zoster in Immunocompetent Patients Over 50 Years of Age: A Cost-Consequence Model,” Pharmacotherapy, 1997, 17(2):333-41.
National Comprehensive Cancer Network® (NCCN), “Clinical Practice Guidelines in Oncology™: Prevention and Treatment of Cancer-Related Infections,” Version 1.2008. Available at http://www.nccn.org/professionals/physician_gls/PDF/infections.pdf
Patel R, Bodsworth NJ, Woolley P, et al, “Valaciclovir for the Suppression of Recurrent Genital HSV Infection: A Placebo Controlled Study of Once Daily Therapy. International Valaciclovir HSV Study Group,” Genitourin Med, 1997, 73(2):105-9.
Perry CM and Faulds D, “Valaciclovir. A Review of Its Antiviral Activity, Pharmacokinetic Properties and Therapeutic Efficacy in Herpesvirus Infections,” Drugs, 1996, 52(5):754-72.
Reitano M, Tyring S, Lang W, et al, “Valaciclovir for the Suppression of Recurrent Genital Herpes Simplex Virus Infection: A Large-Scale Dose Range-Finding Study. International Valaciclovir HSV Study Group,” J Infect Dis, 1998, 178(3):603-10.
Tyring SK, Douglas JM Jr, Corey L, et al, “A Randomized, Placebo-Controlled Comparison of Oval Valacyclovir and Acyclovir in Immunocompetent Patients With Recurrent Genital Herpes Infections. The Valaciclovir International Study Group,” Arch Dermatol, 1998, 134(2):185-91.
“Valacyclovir,” Med Lett Drugs Ther, 1996, 38(965):3-4.
Weller S, Blum MR, Doucette M, et al, “Pharmacokinetics of the Acyclovir Prodrug Valaciclovir After Escalating Single- and Multiple-Dose Administration to Normal Volunteers,” Clin Pharmacol Ther, 1993, 54(6):595-605.
International Brand Names
Lexi-Comp.com
Last full review/revision December 2011
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