Acyclovir

U.S. BRAND NAMES — Zovirax®
CANADIAN BRAND NAMES — Apo-Acyclovir®; Gen-Acyclovir; Nu-Acyclovir; ratio-Acyclovir; Zovirax®
SYNONYMS — Aciclovir; ACV; Acycloguanosine
THERAPEUTIC CATEGORY Antiviral Agent, OralAntiviral Agent, ParenteralAntiviral Agent, Topical
DOSING
(For additional information see "Acyclovir: Drug information")Genital herpes simplex virus (HSV): First infection: Oral: Children: 40-80 mg/kg/day in 3-4 divided doses for 5-10 days; maximum dose: 1 g/day Adolescents and Adults: 200 mg 5 times/day or 400 mg 3 times/day for 5-10 days I.V.: Children and Adults: 5 mg/kg/dose every 8 hours for 5-7 days
Genital HSV infection: Recurrence: Oral: Adolescents and Adults: 200 mg 5 times/day or 400 mg 3 times/day for 5 days
Recurrent genital and cutaneous (ocular) HSV episodes in a patient with frequent recurrences, chronic suppressive therapy: Oral: Children: 40-80 mg/kg/day in 3 divided doses for up to 12 months; maximum dose: 1 g/day; re-evaluate after 12 months of treatment Adolescents and Adults: 400 mg twice daily or 400 mg 3 times/day or 200 mg 3 times/day for as long as 12 continuous months; re-evaluate after 12 months of treatment
HSV in immunocompromised host: Oral: Children:1000 mg/day in 3-5 divided doses for 7-14 days; maximum dose: 80 mg/kg/day not to exceed 1 g/day Adults: 400 mg 5 times/day for 7-14 days I.V.: Children <12 years: 10 mg/kg/dose every 8 hours for 7-14 days Children 12 years and Adults: 5 mg/kg/dose every 8 hours for 7-14 days
Prophylaxis of HSV in immunocompromised host: Oral: Children and Adults: 600-1000 mg/day in 3-5 divided doses during period of risk; maximum dose in children: 80 mg/kg/day not to exceed 1 g/day
HSV encephalitis: I.V.: Children 3 months to 12 years: 20 mg/kg/dose every 8 hours; some clinicians recommend 500 mg/m2/dose every 8 hours for 14-21 days Children >12 years and Adults: 10-15 mg/kg/dose every 8 hours for 14-21 days
Neonatal HSV: I.V.: 20 mg/kg/dose every 8 hours for 14-21 days
Varicella-zoster in immunocompromised host: I.V.: Infants <1 year: 10 mg/kg/dose every 8 hours for 7-10 days Children 1 year: 500 mg/m2/dose every 8 hours for 7-10 days or 10 mg/kg/dose every 8 hours for 7-10 days
Varicella in immunocompetent host: Oral (initiate treatment within the first 24 hours of rash onset): Children 2 years and 40 kg: 20 mg/kg/dose 4 times/day for 5 days; maximum dose: 3200 mg/day Children >40 kg and Adults: 800 mg 4 times/day for 5 days
Zoster in immunocompetent host: Oral (initiate treatment within 48 hours of rash onset): Children 12 years and Adults: 800 mg 5 times/day for 7-10 days
Prophylaxis in bone marrow transplant recipients: I.V.: Autologous patients who are HSV-seropositive: 250 mg/m2/dose every 8 hours Autologous patients who are CMV seropositive: 500 mg/m2/dose every 8 hours; for clinically symptomatic CMV infection, consider replacing acyclovir with ganciclovir
Children and Adults: Topical: Apply 1/2" ribbon of ointment for a 4" square surface area every 3 hours (6 times/day) for 7 days
Dosing interval in renal impairment: Neonates: I.V.: Scr 0.8-1.1 mg/dL: Administer 20 mg/kg/dose every 12 hours Scr 1.2-1.5 mg/dL: Administer 20 mg/kg/dose every 24 hours Scr >1.5 mg/dL: Administer 10 mg/kg/dose every 24 hours Children 6 months and Adults: Oral:
Usual dose: 200 mg 5 times/day: Adjusted dose for Clcr <10 mL/minute: 200 mg every 12 hours Usual dose: 800 mg 5 times/day: Adjusted dose for Clcr 10-25 mL/minute: 800 mg every 8 hours Adjusted dose for Clcr <10 mL/minute: 800 mg every 12 hours I.V.: Clcr 25-50 mL/minute: Administer normal dose every 12 hours Clcr 10-25 mL/minute: Administer normal dose every 24 hours Clcr <10 mL/minute: 50% decrease in dose, administer every 24 hours Hemodialysis: Administer dose after dialysis CVVHD/CVVH: Adjust dose based upon Clcr 30 mL/minute
DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule: 200 mg Zovirax®: 200 mg
Cream, topical: Zovirax®: 5% (2 g, 5 g)
Injection, powder for reconstitution, as sodium: 500 mg, 1000 mg Zovirax®: 500 mg [DSC]
Injection, solution, as sodium [preservative free]: 25 mg/mL (20 mL, 40 mL); 50 mg/mL (10 mL, 20 mL)
Ointment, topical: Zovirax®: 5% (15 g)
Suspension, oral: 200 mg/5 mL (480 mL) Zovirax®: 200 mg/5 mL (480 mL) [banana flavor]
Tablet: 400 mg, 800 mg Zovirax®: 400 mg, 800 mg
GENERIC AVAILABLE — Yes: Excludes cream, ointment
ADMINISTRATION Oral: May administer with food; shake suspension well before use
Parenteral: Reconstitute vial for injection with paraben-free SWI; administer by slow I.V. infusion over at least 1 hour at a final concentration not to exceed 7 mg/mL since rapid infusions can cause nephrotoxicity with crystalluria and renal tubular damage; in patients who require fluid restriction, a concentration of up to 10 mg/mL has been infused; concentration >10 mg/mL increases the risk of phlebitis
USE — Treatment of initial and prophylaxis of recurrent mucosal and cutaneous herpes simplex (HSV 1 and HSV 2) infections; herpes simplex encephalitis; herpes zoster infections; varicella-zoster infections in healthy, nonpregnant persons >13 years of age, children >12 months of age who have a chronic skin or lung disorder or are receiving long-term aspirin therapy, and immunocompromised patients
ADVERSE REACTIONS Central nervous system: Headache, lethargy, delirium, coma, dizziness, seizures, pain, insomnia, fever, hallucinations, aggressive behavior, ataxia
Dermatologic: Skin rash, pruritus, alopecia, erythema multiforme, urticaria, photosensitivity, Stevens-Johnson syndrome, angioedema
Gastrointestinal: Nausea, vomiting, diarrhea
Hematologic: Bone marrow suppression, neutropenia, thrombotic thrombocytopenic purpura/hemolytic uremic syndrome
Hepatic: Elevated liver enzymes, hepatitis, jaundice, hyperbilirubinemia
Local: Phlebitis at injection site, tissue necrosis upon extravasation, local pain and stinging with topical use
Neuromuscular & skeletal: Tremulousness, myalgia, paresthesia
Renal: Nephrotoxicity, hematuria, elevated BUN and serum creatinine
Respiratory: Sore throat
Miscellaneous: Diaphoresis, anaphylaxis
CONTRAINDICATIONS — Hypersensitivity to acyclovir, valacyclovir, or any component
PRECAUTIONS — Use with caution in patients with renal disease, dehydration, underlying neurologic disease, and in patients with hypoxia, hepatic, or electrolyte abnormalities; dosage should be reduced in patients with renal impairment
WARNINGS — HSV and VZV with reduced susceptibility to acyclovir have been isolated from immunocompromised patients, especially with advanced HIV infection; renal failure, in some cases resulting in death, has occurred with acyclovir
DRUG INTERACTIONS — Zidovudine (neurotoxicity); probenecid decreases renal clearance of acyclovir
FOOD INTERACTIONS — Food does not appear to affect absorption
PREGNANCY RISK FACTOR — C (show table)
MONITORING PARAMETERS — Urinalysis, BUN, serum creatinine, I & O; liver enzymes, CBC; neutrophil count at least twice weekly in neonates receiving acyclovir 60 mg/kg/day I.V.
STABILITY — Incompatible with blood products and protein-containing solutions; reconstituted 50 mg/mL solution should be used within 12 hours; do not refrigerate reconstituted solutions as they may precipitate
MECHANISM OF ACTION — Inhibits DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase and by incorporation into viral DNA
PHARMACOKINETICS Absorption: Oral: 15% to 30%
Distribution: Widely distributed throughout the body including brain, kidney, lungs, liver, spleen, muscle, uterus, vagina, and the CSF; CSF acyclovir concentration is 50% of serum concentration; crosses the placenta; excreted into breast milk; Vd: Neonates to 3 months of age: 28.8 L/1.73 m2 Children 1-2 years: 31.6 L/1.73 m2 Children 2-7 years: 42 L/1.73 m2
Protein binding: <30%
Half-life, terminal phase: Neonates: 4 hours Children 1-12 years: 2-3 hours Adults: 2-3.5 hours (with normal renal function)
Time to peak serum concentration: Oral: Within 1.5-2 hours
Elimination: Primary route is the kidney with 30% to 90% of a dose excreted unchanged in the urine; requires dosage adjustment with renal impairment; hemodialysis removes ~60% of a dose while removal by peritoneal dialysis is to a much lesser extent; supplemental dose recommended after hemodialysis
NURSING IMPLICATIONS — Maintain adequate hydration and urine output the first 2 hours after I.V. infusion to decrease the risk of nephrotoxicity; check infusion site for phlebitis; avoid extravasation
ADDITIONAL INFORMATION — Sodium content of 1 g: 4.2 mEq