acyclovir

General

Pronunciation:
ay-sye-kloe-veer

Online audio

Trade Name(s)

• Zovirax

Pregnancy Category
Category B (PO, IV)
Category C (topical)

Ther. Class.
antivirals

Pharm. Class.
purine analogues

Indications

• PO: Recurrent genital herpes infections. Localized cutaneous herpes zoster infections (shingles) and chickenpox (varicella).
• IV: Severe initial episodes of genital herpes in nonimmunosuppressed patients. Mucosal or cutaneous herpes simplex infections or herpes zoster infections (shingles) in immunosuppressed patients. Herpes simplex encephalitis.
• Topical: Cream–Recurrent herpes labialis (cold sores). Ointment–Treatment of limited non–life-threatening herpes simplex infections in immunocompromised patients (systemic treatment is preferred).

Action

Interferes with viral DNA synthesis.

Therapeutic Effect(s):

Inhibition of viral replication, decreased viral shedding, and reduced time for healing of lesions.

Pharmacokinetics

Absorption: Despite poor absorption (15–30%), therapeutic blood levels are achieved.

Distribution: Widely distributed. CSF concentrations are 50% of plasma. Crosses placenta; enters breast milk.

Protein Binding: <30%.

Metabolism and Excretion: >90% eliminated unchanged by kidneys; remainder metabolized by liver.

Half-life: Neonates: 4 hr; Children 1–12 yr: 2–3 hr; Adults: 2–3.5 hr (↑ in renal failure).

TIME/ACTION PROFILE (antiviral blood levels)

Contraindication/Precautions

Contraindicated in:

Hypersensitivity to acyclovir or valacyclovir.

Use Cautiously in:

• Pre-existing serious neurologic, hepatic, pulmonary, or fluid and electrolyte abnormalities
• Renal impairment (dose alteration recommended if CCr <50 mL/min)
• Geri: Due to age related ↓ in renal function
• Obese patients (dose should be based on ideal body weight)
• Patients with hypoxia
• OB: Lactation: Safety not established.

Adverse Reactions/Side Effects

CNS: SEIZURES, dizziness, headache, hallucinations, trembling

GI: diarrhea, nausea, vomiting, ↑ liver enzymes, hyperbilirubinemia, abdominal pain, anorexia

GU: RENAL FAILURE, crystalluria, hematuria, renal pain

Derm: STEVENS-JOHNSON SYNDROME, acne, hives, rash, unusual sweating

Endo: changes in menstrual cycle

Hemat: THROMBOTIC THROMBOCYTOPENIC PURPURA/HEMOLYTIC UREMIC SYNDROME (HIGH DOSES IN IMMUNOSUPPRESSED PATIENTS)

Local: pain, phlebitis, local irritation

MS: joint pain

Misc: polydipsia

* CAPITALS indicate life-threatening.
Italics indicate most frequent.

Interactions

Drug-Drug

• Probenecid ↑ blood levels of acyclovir.
• ↑ blood levels and risk of toxicity from theophylline; dose adjustment may be necessary.
• ↓ blood levels and may ↓ effectiveness of valproic acid or phenytoin.
• Concurrent use of other nephrotoxic drugs ↑ risk of adverse renal effects.
• Zidovudine and IT methotrexate may ↑ risk of CNS side effects.

Route/Dosage

Initial Genital Herpes

PO: (Adults and Children) 200 mg q 4 hr while awake (5 times/day) for 7–10 days or 400 mg q 8 hr for 7–10 days; maximum dose in children: 80 mg/kg/day in 3–5 divided doses.

IV: (Adults and Children) 5 mg/kg q 8 hr or 750 mg/m²/day divided q 8 hr for 5–7 days.

Chronic Suppressive Therapy for Recurrent Genital Herpes

PO: (Adults and Children) 400 mg twice daily or 200 mg 3–5 times/day for up to 12 mo. Maximum dose in children: 80 mg/kg/day in 2–5 divided doses.

Intermittent Therapy for Recurrent Genital Herpes

PO: (Adults and Children) 200 mg q 4 hr while awake (5 times/day) or 400 mg q 8hr or 800 mg q 12 hr for 5 days, start at first sign of symptoms. Maximum dose in children: 80 mg/kg/day in 2–5 divided doses.

Acute Treatment of Herpes Zoster in Immunosuppressed Patients

PO: (Adults) 800 mg q 4 hr while awake (5 times/day) for 7–10 days. Prophylaxis–400 mg 5 times/day.

PO: Children 250–600 mg/m²/dose 4–5 times/day.

Herpes Zoster in Immunocompetent Patients

PO: (Adults and Children) 4000 mg/day in 5 divided doses for 5–7 days, maximum dose in children: 80 mg/kg/day in 5 divided doses.

Chickenpox

PO: (Adults and Children) 20 mg/kg (not to exceed 800 mg/dose) qid for 5 days. Start within 24 hr of rash onset.

Mucosal and Cutaneous Herpes Simplex Infections in Immunosuppressed Patients

IV: (Adults and Children >12 yr): 5 mg/kg q 8 hr for 7 days.

IV: (Children <12 yr): 10 mg/kg q 8 hr for 7 days.

Topical: (Adults) 0.5 in. ribbon of 5% ointment for every 4-square-in. area q 3 hr (6 times/day) for 7 days.

Herpes Simplex Encephalitis

IV: (Adults) 10 mg/kg q 8 hr for 14–21 days.

IV: (Children 3 mo–12 yr): 10 mg/kg q 8 hr for 14–21 days.

IV: (Children birth–3 mo): 20 mg/kg q 8 hr for 14–21 days.

IV: (Neonates , premature): 10 mg/kg q 12 hr for 14–21 days.

Varicella Zoster Infections in Immunosuppressed Patients

IV: (Adults) 10 mg/kg q 8 hr for 7–10 days.

IV: (Children <12 yr): 10 mg/kg q 8 hr for 7–10 days.

Renal Impairment
PO: IV: (Adults and Children) CCr >50 mL/min/1.73 m²–no dosage adjustment needed; CCr 25 –50 mL/min/1.73 m²–administer normal dose q 12 hr; CCr 10–25 mL/min/1.73 m²–administer normal dose q 24 hr; CCr 0–10 mL/min/1.73 m²–50% of dose q 24 hr.

IV: Neonates SCr 0.8–1.1 mg/dL: Administer 20 mg/kg/dose q 12 hr; SCr 1.2–1.5 mg/dL: Administer 20 mg/kg/dose q 24 hr; SCr >1.5 mg/dL: Administer 10 mg/kg/dose q 24 hr.

Herpes labialis

Topical: (Adults and Children >12 yr): Apply 5 times/day for 4 days; start at first symptoms.

Availability (generic available)

Capsules: 200 mg

Tablets: 400 mg, 800 mg

Suspension (banana flavor): 200 mg/5 mL

Powder for injection: 500 mg/vial, 1000 mg/vial

Solution for injection: 25 mg/mL, 50 mg/mL

Cream: 5%

Ointment: 5%

In Combination with: hydrocortisone (Xerese). See combination drugs.

Assessment

• Assess lesions before and daily during therapy.
• Monitor neurologic status in patients with herpes encephalitis.

Lab Test Considerations:

Monitor BUN, serum creatinine, and CCr before and during therapy. ↑ BUN and serum creatinine levels or ↓ CCr may indicate renal failure.

Potential Diagnoses

• Risk for impaired skin integrity (Indications)
• Risk for infection (Patient/Family/Teaching)

Implementation

• Do not confuse Zovirax with Doribax, Zyvox, or Zostrix.
• Start acyclovir treatment as soon as possible after herpes simplex symptoms appear and within 24 hr of a herpes zoster outbreak.
• PO: Acyclovir may be administered with food or on an empty stomach, with a full glass of water.
  • Shake oral suspension well before administration.

Topical: Apply to skin lesions only; do not use in the eye.

Patient/Family Teaching

• Instruct patient to take medication as directed for the full course of therapy. Take missed doses as soon as possible but not just before next dose is due; do not double doses. Acyclovir should not be used more frequently or longer than prescribed.
  • Advise patients that the additional use of OTC creams, lotions, and ointments may delay healing and may cause spreading of lesions.
  • Inform patient that acyclovir is not a cure. The virus lies dormant in the ganglia, and acyclovir will not prevent the spread of infection to others.
  • Advise patient that condoms should be used during sexual contact and that no sexual contact should be made while lesions are present.
  • Patient should consult health care professional if symptoms are not relieved after 7 days of topical therapy or if oral acyclovir does not decrease the frequency and severity of recurrences. Immunocompromised patients may require a longer time, usually 2 weeks, for crusting over of lesions.
  • Instruct women with genital herpes to have yearly Papanicolaou smears because they may be more likely to develop cervical cancer.
• Topical: Instruct patient to apply ointment in sufficient quantity to cover all lesions every 3 hr, 6 times/day for 7 days. 0.5-in. ribbon of ointment covers approximately 4 square in. Use a finger cot or glove when applying to prevent inoculation of other areas or spread to other people. Keep affected areas clean and dry. Loose-fitting clothing should be worn to prevent irritation.
  • Avoid drug contact in or around eyes. Report any unexplained eye symptoms to health care professional immediately; ocular herpetic infection can lead to blindness.

Evaluation/Desired Outcomes

• Crusting over and healing of skin lesions.
• Decrease in frequency and severity of recurrences.
• Acceleration of complete healing and cessation of pain in herpes zoster.
• Decrease in intensity of chickenpox.