acyclovir (acycloguanosine)

acyclovir sodium
Zovirax

Available forms
Available by prescription only
Capsules: 200 mg
Injection: 500 mg/vial, 1 g/vial
Injection concentrate for I.V. infusion: 50 mg/ml
Ointment: 5%
Oral suspension: 200 mg/5 ml
Tablets: 400 mg, 800 mg

Indications and dosages
 Initial and recurrent mucocutaneous herpes simplex virus (HSV) type 1 and type 2 or severe initial genital herpes or herpes simplex in immunocompromised patients. Adults and children older than age 12: 5 mg/kg, given at a constant rate over 1 hour by I.V. infusion q 8 hours for 7 days (5 days for genital herpes).
Children younger than age 12: 10 mg/kg infused at a constant rate over 1 hour by I.V. infusion q 8 hours for 7 days (5 days for genital herpes).
 Mucocutaneous HSV type 1 and HSV type 2 in immunocompromised patients. Adults: 400 mg P.O. q 4 hours while awake (five times daily).
Children: 1 g P.O. daily divided into three to five doses for 7 to 14 days; dose shouldn’t exceed 80 mg/kg daily.
 Disseminated herpes zoster. ◇ Adults: 5 to 10 mg/kg I.V. q 8 hours for 7 to 10 days. Infuse over at least 1 hour.
 Initial genital herpes. Adults: 200 mg P.O. q 4 hours while awake (a total of five capsules daily). Treatment should continue for 10 days. Or, 400 mg P.O. t.i.d. for 7 to 10 days.
 Genital herpes in immunocompromised patients. ◇ Adults: 400 mg P.O. three to five times daily.
 Rectal herpes infection. ◇ Adults: 400 mg P.O. five times daily for 10 days or until resolution; or, 800 mg P.O. q 8 hours for 7 to 10 days for initial infections.
 Acute herpes zoster infection. Adults: 800 mg P.O. five times daily for 7 to 10 days. Start therapy within 48 hours of rash onset.
 Intermittent therapy for recurrent genital herpes. Adults: 200 mg P.O. q 4 hours while awake (a total of five capsules daily). Continue treatment for 5 days. Start therapy at first sign of recurrence.
 Long-term suppressive therapy for recurrent genital herpes. Adults: 400 mg P.O. b.i.d. for up to 1 year, followed by reevaluation.
 Genital herpes; non-life-threatening herpes simplex infection in immunocompromised patients. Adults and children: Apply sufficient quantity of ointment to adequately cover all lesions q 3 hours, six times daily for 7 days.
 Neonatal herpes simplex virus infection. Neonates and infants up to 3 months: 10 mg/kg I.V. q 8 hours for 10 days.
Preterm neonates: 10 mg/kg I.V. q 12 hours.
 Primary or recurrent HSV infections in patients with HIV. Adults: 200 to 800 mg P.O. five times daily.
 Long-term suppressive or maintenance prophylaxis therapy for recurrent HSV infections in patients with HIV. ◇ Adults and adolescents: 200 mg P.O. t.i.d. or 400 mg P.O. b.i.d.
Infants and children: 600 to 1,000 mg P.O. daily in three to five divided doses; alternatively, 80 mg/kg in three to four divided doses.
 Acute varicella (chickenpox) infections. Adults and children age 2 and older who weigh more than 40 kg (88 lb): 800 mg P.O. q.i.d. for 5 days.
Children age 2 and older who weigh less than 40 kg: 20 mg/kg P.O. q.i.d. for 5 days.
 Acute herpes zoster ophthalmicus. ◇ Adults: 600 mg P.O. q 4 hours five times daily for 10 days; within 7 days of rash onset, but preferably within 72 hours.
 Varicella in immunocompromised patients. Adults and children older than age 12: 10 mg/kg I.V. over 1 hour q 8 hours for 7 days.
Children younger than age 12: 20 mg/kg I.V. over 1 hour q 8 hours for 7 days.
 Herpes simplex encephalitis. Adults and children older than age 12: 10 mg/kg I.V. over 1 hour q 8 hours for 10 days.
Children ages 3 months to 12 years: 20 mg/kg q 8 hours I.V. over at least 1 hour for 10 days.
≡ Dosage adjustment. For patients with renal failure, adjust normal oral dose (200 to 400 mg) to 200 mg q 12 hours if creatinine clearance drops below 10 ml/minute. If patient is on a regimen of 800 mg q 4 hours five times daily, give 800 mg P.O. q 8 hours if creatinine clearance is 10 to 25 ml/minute, or 800 mg P.O. q 12 hours if creatinine clearance is less than 10 ml/minute.
 For patients with renal failure, give 100% of the I.V. dose q 8 hours if creatinine clearance exceeds 50 ml/minute. Give 100% of the dose q 12 hours if it’s 25 to 50 ml/minute. Give 100% of the dose q 24 hours if it’s 10 to 25 ml/minute. Give 50% of the dose q 24 hours if it falls below 10 ml/minute.

Pharmacodynamics
Antiviral action: Acyclovir is converted by the viral cell into its active form (triphosphate) and inhibits viral DNA polymerase. In vitro, acyclovir is active against HSV type 1, HSV type 2, varicella-zoster virus, Epstein-Barr virus, and cytomegalovirus. In vivo, acyclovir may reduce the duration of acute infection and speed lesion healing in initial genital herpes episodes. Patients with frequent herpes recurrences (more than six episodes a year) may receive oral acyclovir prophylactically to prevent recurrences or reduce their frequency.

Pharmacokinetics
Absorption: Oral form absorbed slowly and incompletely (15% to 30%). Absorption isn’t affected by food. With topical administration, absorption is minimal.
Distribution: Distributed widely to organ tissues and body fluids. CSF levels equal about 50% of serum levels. About 9% to 33% of a dose binds to plasma proteins.
Metabolism: Metabolized inside the viral cell to its active form. About 10% of dose is metabolized extracellularly.
Excretion: Up to 92% of systemically absorbed acyclovir is excreted as unchanged drug by the kidneys by glomerular filtration and tubular secretion. In patients with normal renal function, half-life is 2 to 31/2 hours. Renal failure may extend half-life to 19 hours.

Contraindications and precautions
Contraindicated in patients hypersensitive to drug. Use cautiously in patients with underlying neurologic problems, renal disease, or dehydration and in those receiving nephrotoxic drugs.

Interactions
Drug-drug. Methotrexate: May cause reaction in patients who have had a previous neurologic reaction to intrathecal methotrexate administration. Use I.V. acyclovir cautiously in these patients.
Probenecid: May reduce renal tubular secretion of acyclovir, leading to increased drug half-life, reduced elimination rate, and decreased urine excretion. This reduced clearance causes more sustained serum drug level. Avoid use together.
Zidovudine: May result in increased levels of acyclovir, causing toxicity. Monitor acyclovir levels closely.

Adverse reactions
CNS: encephalopathic changes (lethargy, obtundation, tremor, confusion, hallucinations, agitation, seizures, coma), headache, malaise.
CV: phlebitis.
GI: diarrhea, nausea, vomiting.
GU: hematuria, renal impairment, vulvitis.
Hematologic: bone marrow hypoplasia, leukopenia, megaloblastic hematopoiesis, thrombocytosis, thrombocytopenia.
Skin: itching, rash, transient burning and stinging, pruritus, urticaria, inflammation at injection site.

Effects on lab test results
• May increase BUN and creatinine levels.
• May decrease WBC count. May increase or decrease platelet count.

Overdose and treatment
Evidence of overdose includes signs of nephrotoxicity, including elevated serum creatinine and BUN levels, progressing to renal failure. Overdose has followed I.V. bolus administration in patients with unmonitored fluid status or in patients receiving inappropriately high parenteral dosages. Acute toxicity hasn’t been reported after high oral dosage.
 Hemodialysis results in 60% decrease in plasma drug level.

Special considerations
 ALERT Don’t confuse Zovirax (acyclovir) with Zyvox (linezolid). Both are available as a 600-mg tablet.
• Drug shouldn’t be given by S.C., I.M., or ophthalmic route or by I.V. bolus.
• Reconstitute drug by adding 10 to 20 ml of sterile water for injection to a 500 mg or 1 g acyclovir vial, respectively, to provide a solution containing 50 mg/ml. Don’t use bacteriostatic water for injection. Use reconstituted solution within 12 hours. Further dilute in 50 to 125 ml of a compatible I.V. solution to no more than 7 mg/ml.
• Infuse I.V. dose over at least 1 hour to prevent renal tubular damage.
• Solubility of acyclovir in urine is low. Make sure patient taking the systemic form of drug is well hydrated to prevent nephrotoxicity.
• Don’t apply topical preparation to vagina or cervix.
• Monitor serum creatinine level. If level doesn’t return to normal within a few days after therapy begins, increase hydration, adjust dose, or discontinue drug.
• Monitor patient for encephalopathic signs; they’re more likely in patients who have experienced neurologic reactions to cytotoxic drugs.
Pregnant patients
• Use only if benefits outweigh the risks.
Pediatric patients
• Safety and effectiveness of oral and topical acyclovir in children haven’t been established.
• I.V. acyclovir has been used in only a few children.
• To reconstitute acyclovir for children, don’t use bacteriostatic water for injection that contains benzyl alcohol.
Geriatric patients
• Administer drug cautiously to geriatric patients because they have an increased risk of renal dysfunction or dehydration.

Patient education
• Warn patient that although drug helps manage the disease, it doesn’t cure it or prevent its spread to others.
• Tell patient to begin taking drug when early infection symptoms occur, such as tingling, itching, or pain.
• Instruct patient taking ointment to use a finger cot or rubber glove and to apply about 1/4-inch ribbon of ointment for every 4 square inches of area to be covered. Ointment should thoroughly cover each lesion. Warn patient to avoid getting ointment in eyes.
• Instruct patient to avoid sexual intercourse during active genital infection.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use