Valacyclovir Hydrochloride

Pronunciation

Pronunciation: VAL-ay-SYE-kloe-vir HYE-droe-KLOR-ide
Class: Antiherpes virus agent

Trade Names

Valtrex
- Tablets 500 mg
- Tablets 1 g

Pharmacology

Converted to acyclovir, which then inhibits viral DNA replication by interfering with viral DNA polymerase.

Slideshow: Flashback: FDA Drug Approvals 2013

Pharmacokinetics

Absorption

Rapidly absorbed from the GI tract. Bioavailability is about 55%.

C max ranges from 0.83 to 5.65 mcg/mL, depending on the dose.

Distribution

Protein binding ranges from 14% to 18%.

Metabolism

Converted to acyclovir and/or L-valine by first-pass intestinal or hepatic metabolism.

Elimination

About 46% is recovered in urine. About 47% is recovered in feces. Elimination half-life is approximately 2.5 to 3.3 h.

Special Populations

Renal Function Impairment

Dose reduction is recommended.

Hepatic Function Impairment

Dose modification is not recommended in patients with cirrhosis.

Elderly

Dose modification may be necessary in elderly patients with reduced renal function.

Children

C max approximately 4.2 mcg/mL in children 1 month to younger than 12 yr of age.

Indications and Usage

Adults

Treatment of cold sores (herpes labialis); treatment of initial and recurrent episodes of genital herpes in immunocompetent patients; suppression of recurrent episodes of genital herpes in immunocompetent and HIV-infected patients; reduction of transmission of genital herpes in immunocompetent patients; treatment of herpes zoster (shingles) in immunocompetent adults.

Children

Treatment of cold sores in children 12 yr of age and older; treatment of chickenpox in immunocompetent patients 2 to 18 yr of age.

Contraindications

Clinically important hypersensitivity reaction (eg, anaphylaxis) to valacyclovir, acyclovir, or any component of the product.

Dosage and Administration

Acute or Chronic Renal Function Impairment
Adults

PO

  • Herpes zoster: CrCl 30 to 49 mL/min, give 1 g every 12 h; CrCl 10 to 29 mL/min, give 1 g every 24 h; CrCl less than 10 mL/min, give 500 mg every 24 h.
  • Genital herpes (initial episode): CrCl 10 to 29 mL/min, give 1 g every 24 h; CrCl less than 10 mL/min, give 500 mg every 24 h.
  • Genital herpes (recurrent episodes): CrCl 29 mL/min or less, give 500 mg every 24 h.
  • Genital herpes (suppressive therapy): CrCl 29 mL/min or less, give 500 mg every 24 h. In patients with a history of 9 or fewer recurrences per year and CrCl 29 mL/min or less, give 500 mg every 48 h.
  • Genital herpes suppressive therapy in HIV-infected patients: CrCl 29 mL/min or less, give 500 mg every 24 h.
  • Herpes labialis (do not exceed 1 day of treatment): CrCl 30 to 49 mL/min, give two 1 g doses about 12 h apart; CrCl 10 to 29 mL/min, give two 500 mg doses about 12 h apart; CrCl less than 10 mL/min, give 500 mg as a single dose.
Chickenpox
Children 2 to younger than 18 yr of age

PO 20 mg/kg administered 3 times daily for 5 days (max, 1 g 3 times daily). Initiate therapy at earliest sign or symptom.

Genital Herpes
Adults HIV-infected patients

PO 500 mg twice daily for suppressive therapy in HIV-infected patients with CD4 cell count of at least 100 cells/mm 3 (efficacy beyond 6 mo of therapy has not been established).

Initial episodes

PO 1 g twice daily for 10 days (initiate therapy within 48 h of onset of signs and symptoms).

Recurrent episodes

PO 500 mg twice daily for 3 days (initiate therapy at first sign or symptom).

Reduction of transmission

PO 500 mg once daily for the source partner in patients with a history of 9 or fewer recurrences per year.

Suppressive therapy

PO 1 g once daily. In patients with a history of 9 or fewer recurrences per year, 500 mg/day may be administered.

Hemodialysis

PO Administer the recommended dose after hemodialysis

Herpes Labialis
Adults

PO 2 g twice daily for 1 day approximately 12 h apart, initiated at earliest symptoms of cold sore (eg, tingling, burning, itching).

Children 12 yr of age and older

PO 2 g twice daily for 1 day taken 12 h apart. Initiate therapy at earliest symptoms of a cold sore.

Herpes Zoster
Adults

PO 1 g 3 times daily for 7 days (initiate therapy within 48 h of onset of rash or at earliest sign or symptom).

General Advice

  • May be given with or without food.
  • Prepare suspensions at the time of dispensing according to the manufacturer's instructions.
  • Initiate treatment of chickenpox within 24 h after the onset of rash.

Storage/Stability

Store at controlled room temperature (59° to 77°F).

Drug Interactions

Probenecid

Increased acyclovir serum concentrations.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypertension, tachycardia (postmarketing).

CNS

Headache (38%); fatigue (8%); depression (7%); dizziness, pyrexia (4%); aggressive behavior, agitation, ataxia, coma, confusion, decreased consciousness, dysarthria, encephalopathy, mania, psychosis (including audio and visual hallucinations), seizures, tremors (postmarketing).

Dermatologic

Rash (8%); alopecia, erythema multiforme, rashes (including photosensitivity) (postmarketing).

EENT

Nasopharyngitis (16%); visual abnormalities (postmarketing).

GI

Nausea (15%); abdominal pain (11%); vomiting (6%); diarrhea (5%).

Genitourinary

Dysmenorrhea (8%); renal failure (postmarketing).

Hematologic-Lymphatic

Aplastic anemia, hemolytic uremic syndrome, leukocytoclastic vasculitis, thrombocytopenia, thrombocytopenic purpura (postmarketing).

Hepatic

Hepatitis (postmarketing).

Lab Tests

Decreased neutrophil counts (18%); increased AST (16%); increased ALT (14%); elevated alkaline phosphatase (4%); decreased platelet counts (3%); decreased hemoglobin, increased serum creatinine, leukopenia (1%).

Metabolic-Nutritional

Dehydration (2%).

Respiratory

Rhinorrhea (2%).

Miscellaneous

Arthralgia (6%); herpes simplex (2%); acute hypersensitivity reactions (including anaphylaxis, angioedema, dyspnea, pruritus, rash, and urticaria), facial edema (postmarketing).

Precautions

Pregnancy

Category B .

Lactation

Undetermined (acyclovir is excreted in breast milk).

Children

Safety and efficacy not established in children younger than 12 yr of age with cold sores; younger than 18 yr of age with genital herpes or herpes zoster; younger than 2 yr of age with chickenpox.

Elderly

Dosage reduction may be necessary, depending on underlying renal status.

Renal Function

Dosage reduction is recommended; exercise caution when giving valacyclovir to patients with renal function impairment or those receiving potentially nephrotoxic drugs.

Acute renal failure

Has occurred in elderly patients; patients with underlying renal disease who received higher than recommended doses for their level of renal function; patients receiving other nephrotoxic drugs; and patients without adequate hydration.

CNS adverse reactions

CNS reactions, including agitation, confusion, delirium, encephalopathy, hallucinations, and seizures, have been reported in elderly patients with and without reduced renal function and in patients with underlying renal disease who received higher than recommended doses for their level of renal function.

Immunocompromised

Safety and efficacy not established in immunocompromised patients other than for the suppression of genital herpes in HIV-infected patients.

Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome

May occur and has resulted in death in patients with advanced HIV disease and also in allogenic bone marrow and renal transplant recipients receiving valacyclovir 8 g/day.

Overdosage

Symptoms

Acute renal failure, anuria.

Patient Information

  • Review dose and appropriate dosing schedule depending on condition being treated (shingles, cold sores, or genital herpes). Instruct patient to take medication exactly as prescribed and not to stop taking or change the dose unless advised by health care provider.
  • Advise patients to initiate treatment at the earliest signs and symptoms of chickenpox.
  • Advise patient that medication can be taken without regard to meals, but to take with food if stomach upset occurs.
  • Advise patients to maintain adequate hydration.
  • Remind patient using medication for cold sores that it is not a cure and to initiate therapy at the first symptom of a cold sore (eg, tingling, itching, burning). Remind patient that treatment should not exceed 2 doses taken about 12 h apart.
  • Remind patient using medication for recurrent episodes of genital herpes to initiate therapy at the first sign or symptom of recurrence and that medication may not be effective if started more than 24 h after onset of signs or symptoms of recurrence.
  • Inform patient that there are no data on treatment of herpes zoster when initiated more than 72 h after the onset of the zoster rash.
  • Advise patient with genital herpes that this drug is not a cure for genital herpes and does not prevent transmission of virus. Instruct patient to avoid sexual intercourse when lesions and/or symptoms are present to avoid infecting partner.
  • Advise patient to contact health care provider if medication does not seem to be controlling lesions and/or symptoms, or if intolerable adverse reactions develop.
  • Caution patient to avoid unnecessary exposure to UV light (sunlight, tanning booths) and to use sunscreen and wear protective clothing until tolerance is determined.

Copyright © 2009 Wolters Kluwer Health.

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