Acyclovir

Pronunciation: A-SIKE-low-vihr
Class: Antiherpes virus agent, Antiviral

Trade Names

Acyclovir
- Injection 50 mg/mL (as sodium)
- Powder for injection 500 mg/vial (as sodium)
- Powder for injection 1,000 mg/vial (as sodium)

Zovirax
- Tablets 400 mg
- Tablets 800 mg
- Capsules 200 mg
- Suspension 200 mg per 5 mL
- Ointment 5%
- Cream 5%

Apo-Acyclovir (Canada)
Gen-Acyclovir (Canada)
Nu-Acyclovir (Canada)
ratio-Acyclovir (Canada)

Pharmacology

Inhibits viral DNA replication by interfering with viral DNA polymerase.

Pharmacokinetics

Absorption

Oral

Bioavailability is 10% to 20%. C max is 0.83 to 1.61 mcg/mL (200 to 800 mg at steady state).

IV

C max is 9.8 mcg/mL (5 mg/kg dose), 22.9 mcg/mL (10 mg/kg).

Topical

Systemic absorption is minimal.

Distribution

9% to 33% protein bound.

IV

CSF concentrations are about 50% of plasma values.

Elimination

The t ½ is 2.5 to 3.3 h. Cl and t ½ are dependent on renal function.

IV

62% to 91% is excreted unchanged in the urine. Cl is 5.1 mL/min/kg.

Special Populations

Renal Function Impairment

Total body Cl and t ½ are dependent on renal function. Dosage adjustment recommended.

Elderly

Increased plasma concentrations. Dosage adjustment may be required.

Indications and Usage

Parenteral

Treatment of initial or recurrent mucosal and cutaneous herpes simplex viruses (HSV) and varicella zoster (shingles) infections in immunocompromised patients; treatment of herpes simplex encephalitis; treatment of severe initial clinical episodes of genital herpes; treatment of neonatal herpes infections.

Oral

Treatment of initial and recurrent episodes of genital herpes in certain patients; acute treatment of shingles and chickenpox.

Topical

Treatment of initial episodes of herpes genitalis and nonlife-threatening mucotaneous HSV infections in immunocompromised patients (ointment); recurrent herpes labialis (cold sores) (cream).

Unlabeled Uses

Treatment of cytomegalovirus and HSV infection after bone marrow or renal transplant; treatment of infectious mononucleosis, varicella pneumonia, chickenpox, and other HSV infections.

Contraindications

Hypersensitivity to acyclovir or valacyclovir.

Dosage and Administration

Parenteral

For IV infusion only; rapid or bolus IV must be avoided.

Herpes Simplex Infections in Immunocompromised Patients Adults and adolescents 12 yr of age and older

IV 5 mg/kg infused at a constant rate over 1 h every 8 h for 7 days.

Children younger than 12 yr of age

IV 10 mg/kg infused at a constant rate over 1 h every 8 h for 7 days.

Severe Initial Genital Herpes Adults and adolescents 12 yr of age and older

IV 5 mg/kg at a constant rate over 1 h every 8 h for 5 days.

Varicella Zoster Infections in Immunocompromised Patients Adults and adolescents 12 yr of age and older

IV 10 mg/kg infused at a constant rate over 1 h every 8 h for 7 days.

Children younger than 12 yr of age

IV 20 mg/kg infused at a constant rate over 1 h every 8 h for 7 days.

Herpes Simplex Encephalitis Adults and adolescents 12 yr of age and older

IV 10 mg/kg infused at a constant rate over 1 h every 8 h for 10 days.

Children 3 mo to 12 yr of age

IV 20 mg/kg infused at a constant rate over 1 h every 8 h for 10 days.

Neonatal Herpes Infections (CDC Recommendations)

IV Disseminated and CNS disease: 20 mg/kg every 8 h for 21 days. Mucocutaneous disease: 20 mg every 8 h for 14 days.

Oral
Chickenpox Adults and children (greater than 40 kg)

PO 800 mg 4 times daily for 5 days.

Children 2 yr of age and older (40 kg or less)

PO 20 mg/kg 4 times daily for 5 days.

Herpes Zoster Adults

PO 800 mg every 4 h 5 times/day for 7 to 10 days.

Initial Genital Herpes Adults

PO 200 mg every 4 h 5 times/day for 10 days.

Suppressive Therapy for Recurrent Genital Herpes Adults

PO 400 mg bid for up to 12 mo.

Intermittent Therapy for Recurrent Genital Herpes Adults

PO 200 mg every 4 h 5 times/day for 5 days at earliest sign or symptom of recurrence.

Topical
Initial Genital Herpes and Herpes Simplex Infections in Immunocompromised Patients Adults

Ointment Apply sufficient quantity to cover all lesions every 3 h, 6 times/day, for 7 days.

Recurrent Herpes Labialis (Cold Sores) Adults and children 12 yr of age and older

Cream Apply to lesion 5 times/day for 4 days.

General Advice

  • Injection
  • Reconstitute powder for injection, following manufacturer's guidelines, with sterile water for injection to produce a solution containing 50 mg/mL.
  • Further dilute prescribed dose in any appropriate IV solution at a volume selected for administration over 1 h.
  • Infuse prescribed dose over a period of at least 1 h to reduce risk of renal tubular damage.
  • Do not administer if particulate matter, cloudiness, or discoloration noted.
  • Discard any unused solution. Do not save for future use.

Storage/Stability

Oral

Store tablets, capsules, and suspension at controlled room temperature (59° to 77°F). Protect from moisture.

Topical

Store ointment at controlled room temperature (59° to 77°F). Store cream at controlled room temperature (59° to 86°F).

Injection

Store powder for injection at controlled room temperature (59° to 77°F). Use reconstituted solution within 12 h. Refrigeration of reconstituted solution may result in formation of a precipitate that will redissolve at room temperature. Use diluted solution within 24 h.

Drug Interactions

Probenecid

IV acyclovir plasma levels may be increased, and the duration of action prolonged, while the urinary excretion and renal Cl may be reduced.

Zidovudine

Increased propensity for lethargy.

Incompatibility

Precipitation may occur with bacteriostatic water. Do not add acyclovir to biologic or colloidal fluids.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Phlebitis at injection site (9%); hypotension (postmarketing).

CNS

Headache, agitation, coma, confusion, delirium, dizziness, hallucinations, obtundation, psychosis, seizure, somnolence (postmarketing).

Dermatologic

Itching, rash, hives (2%); alopecia, erythema multiforme, photosensitive rash, pruritus, rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria (postmarketing).

EENT

Visual abnormalities.

GI

Nausea, vomiting (7%); diarrhea, GI distress, abdominal pain (postmarketing).

Genitourinary

Transient elevations of serum creatinine or BUN (5% to 10%); renal failure, elevated blood urea nitrogen, elevated creatinine.

Hematologic

Anemia, neutropenia, thrombocytopenia, thrombocytosis, leukocytosis, neutrophilia (less than 1%); leukopenia (postmarketing).

Hematologic-Lymphatic

Disseminated intravascular coagulation, hemolysis, lymphadenopathy (postmarketing).

Hepatic

Elevated transaminases (1% to 2%); hepatitis, jaundice (postmarketing).

Musculoskeletal

Myalgia (postmarketing).

Miscellaneous

Anaphylaxis, fever, pain, peripheral edema (postmarketing).

Precautions

Pregnancy

Category B .

Lactation

Excreted in breast milk.

Children

Oral

Safety and efficacy in children under 2 yr of age not established.

Topical

Safety and efficacy not established in pediatric patients.

Elderly

Use with caution because of the greater frequency of decreased hepatic, renal, or cardiac function, and concomitant diseases or other drug therapy.

Renal Function

Dosage adjustment may be needed. With parenteral use, acyclovir may precipitate as crystals in renal tubules.

Chickenpox

Chickenpox in otherwise healthy children is usually a self-limiting disease of mild to moderate severity; however, adolescents and adults tend to have more severe disease.

Cutaneous use

Care must be taken to avoid getting drug in eyes.

Encephalopathic changes

Patients with underlying neurologic abnormalities or severe hypoxia may have increased risk of neurotoxic effects.

Genital herpes

Sexual intercourse must be avoided when lesions are present. Use of acyclovir does not prevent transmission.

Herpes zoster infection

There are no data on treatment started more than 72 h after the onset of the rash.

IV acyclovir

Ensure that patient receiving IV acyclovir is well hydrated during therapy and that max dose of 20 mg/kg every 8 h is not exceeded.

Thrombotic thrombocytopenic purpura/Hemolytic uremic syndrome

May occur and has resulted in death in immunocompromised patients.

Overdosage

Symptoms

Increased BUN and serum creatinine, renal failure, convulsions, lethargy, acyclovir precipitation, renal tubules, agitation, coma.

Patient Information

  • Injection
  • Advise patient, family, or caregiver that medication will be prepared and administered by a health care provider in a health care setting.
  • Advise patient, family, or caregiver to report injection site pain or redness.
  • Topical
  • Advise patient not to cover the cold sore with a bandage or dressing.
  • Advise patient that the cream dose form is not to be used for genital herpes.
  • Advise patient or caregiver using ointment to use finger cot or rubber glove when applying to prevent spread of infection and to wash hands with soap and water after applying ointment.
  • Advise patient or caregiver to apply enough ointment to adequately cover all lesions every 3 h (6 times/day) for 7 days. Advise patient or caregiver that a ½ inch ribbon of ointment should cover about 4 square inches.
  • Advise patient or caregiver using cream to apply to lesions 5 times/day for 4 days and to wash hands with soap and water after each application.
  • Advise patient or caregiver to notify health care provider if lesions do not appear to be improving, are getting worse, or if application site reactions (eg, burning, stinging, redness, itching) develop.
  • Tablets, capsules, or suspension
  • Review dose and appropriate dosing schedule depending on condition being treated (shingles, chickenpox, recurrent 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 patient that medication can be taken without regard to meals but to take with food if stomach upset occurs.
  • Advise patient or caregiver using suspension to shake it well before measuring dose and to measure and administer prescribed dose using a dosing syringe, dosing dropper, or medicine cup.
  • Remind patient using medication for recurrent episodes of genital herpes to initiate therapy at the first sign or symptom or recurrence and that medication may not be effective if started more than 6 h after onset of signs or symptoms of recurrence.
  • 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 side effects develop.

Copyright © 2009 Wolters Kluwer Health.

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