Version May 2024
Dosage guidance:
Safety: To avoid overdosing and subsequent toxicity (eg, acute renal failure), use ideal body weight or adjusted body weight for weight-based dosing in patients with obesity (Ref).
Bell palsy, new onset (adjunctive therapy) (alternative agent) (off-label use): Oral: 400 mg 5 times daily for 10 days in combination with corticosteroids; begin within 3 days of symptom onset. Note: Antiviral therapy alone is not recommended (Ref); some experts only recommend addition of an antiviral to steroid therapy in patients with severe Bell palsy (Ref).
Cytomegalovirus, prevention in recipients of allogeneic hematopoietic cell transplant (alternative agent) (off-label use): Note: Begin at engraftment and continue to day 100; requires close monitoring for cytomegalovirus (CMV) reactivation (due to weak activity) (Ref):
IV: 500 mg/m2/dose every 8 hours for up to 4 weeks or until hospital discharge, followed by oral therapy (Ref).
Oral: Following initial IV therapy: 800 mg 4 times daily (Ref).
Herpes simplex virus, central nervous system infection (encephalitis or meningitis): IV: 10 mg/kg/dose every 8 hours. Duration for encephalitis is 14 to 21 days and for meningitis is 10 to 14 days; treatment of encephalitis requires IV therapy while treatment of meningitis may include step-down oral antiviral therapy. Note: Empiric herpes simplex virus (HSV) therapy should be initiated in all patients with suspected encephalitis (Ref).
Herpes simplex virus, mucocutaneous infection:
Esophagitis (off-label use):
Patients who are immunocompetent: Oral: 400 mg 3 times daily or 200 mg 5 times daily for 7 to 10 days (Ref).
Patients who are immunocompromised: Oral: 400 mg 5 times daily for 14 to 21 days (Ref).
Patients with severe odynophagia or dysphagia: IV: 5 mg/kg/dose every 8 hours; patients who rapidly improve can be switched to an oral antiviral to complete a total of 7 to 14 days of therapy (Ref).
Genital:
Patients who are immunocompetent:
Treatment, initial episode:
Oral: 400 mg 3 times daily for 7 to 10 days; extend duration if lesions have not healed completely after 10 days (Ref).
IV (for severe disease): 5 to 10 mg/kg/dose every 8 hours; once clinically improved, may switch to oral antiviral therapy to complete >10 days of therapy total (Ref).
Treatment, recurrent episode: Oral: 800 mg twice daily for 5 days or 800 mg 3 times daily for 2 days. Note: Treatment is most effective when initiated during the prodrome or within 1 day of lesion onset (Ref).
Suppressive therapy (eg, for severe and/or frequent recurrences): Oral: 400 mg twice daily. Note: Reassess need periodically (eg, annually) (Ref).
Patients who are immunocompromised (including patients with HIV):
Treatment, initial or recurrent episode:
Oral: 400 mg 3 times daily for 5 to 10 days (7 to 10 days for initial episode in patients with HIV); extend treatment duration if lesions have not healed completely after 10 days (Ref).
IV (for severe disease): 5 to 10 mg/kg/dose every 8 hours; may transition to oral antiviral therapy once lesions begin to regress and continue for >10 days of therapy and until complete resolution (Ref).
Suppressive therapy (eg, for severe and/or frequent recurrences): Oral: 400 to 800 mg 2 to 3 times daily. Note: Reassess need periodically (eg, annually) (Ref).
Pregnant patients:
Treatment, initial episode: Oral: 400 mg 3 times daily for 7 to 10 days; extend treatment duration if lesion has not healed completely after 10 days (Ref).
Treatment, recurrent episode (symptomatic): Oral: 400 mg 3 times daily or 800 mg twice daily for 5 days or 800 mg 3 times daily for 2 days (Ref). Note: Some experts reserve treatment of recurrent episodes for patients with severe and/or frequent symptoms (Ref).
Treatment, severe or disseminated disease: IV: 5 to 10 mg/kg every 8 hours for 2 to 7 days, then change to oral therapy for primary infection to complete 10 days of therapy (Ref).
Suppressive therapy, for patients with a genital HSV lesion anytime during pregnancy: Oral: 400 mg 3 times daily (Ref), beginning at 36 weeks' gestation and continued until delivery (Ref); some experts recommend discontinuing suppressive therapy at the onset of labor (Ref). Note: For patients with a primary infection during the third trimester, may consider suppressive therapy earlier than 36 weeks' gestation (Ref).
Orolabial: Note: Initiate therapy at earliest symptom.
Patients who are immunocompetent and immunocompromised (including patients with HIV):
Treatment, initial or recurrent episode:
Oral: 400 mg 3 times daily for 5 to 10 days and until complete lesion resolution in patients who are immunocompromised (Ref).
IV (for severe disease in immunocompromised patients): 5 mg/kg/dose every 8 hours; switch to oral acyclovir (or similar antiviral) once lesions begin to regress and continue until complete resolution (Ref).
Suppressive therapy (eg, for severe and/or frequent recurrences): Oral: 400 mg twice daily (Ref). Note: Reassess need periodically (eg, annually) (Ref).
Herpes simplex virus, prevention in patients who are immunocompromised (off-label use):
Seropositive hematopoietic cell transplant recipients (allogeneic or autologous) or seropositive patients undergoing leukemia induction chemotherapy:
IV: 250 mg/m2/dose every 12 hours (Ref).
Oral: 400 to 800 mg twice daily (Ref).
Note: Initiate with the chemotherapeutic or conditioning regimen and continue until recovery of WBC count and resolution of mucositis; duration may be extended in patients with frequent recurrences or graft-vs-host disease (Ref).
Solid organ transplant recipients (HSV-seropositive patients who do not require CMV prophylaxis): Oral: 400 to 800 mg twice daily for ≥1 month (Ref); some experts recommend continuing for 3 to 6 months after transplantation and during periods of lymphodepletion associated with treatment of rejection (Ref).
Herpes zoster (shingles), treatment:
Note: Initiate at earliest sign or symptom. Antiviral treatment is most effective ≤72 hours after rash onset but may be initiated >72 hours in certain situations (eg, new lesions continue to appear); for patients who are immunocompromised, initiate treatment even if >72 hours after symptom onset unless all lesions have crusted (Ref).
Acute localized dermatomal lesion(s): Oral: 800 mg 5 times daily for 7 to 10 days; for slowly improving lesions, may extend therapy until resolution (Ref). For select patients who are immunocompromised at high risk of dissemination (eg, recent transplant, graft-versus-host disease), some experts suggest regimens used for disseminated zoster (Ref).
Disseminated zoster (extensive cutaneous lesions or visceral involvement): IV: 10 mg/kg/dose every 8 hours (Ref). When formation of new lesions has ceased and signs/symptoms of visceral infection are improving, switch to an oral antiviral to complete a total of 10 to 14 days of therapy (Ref).
Varicella (chickenpox), treatment: Ideally initiate therapy within 24 hours of symptom onset, but may start later if the patient still has active lesions:
Severe or complicated infection: IV: 10 mg/kg/dose every 8 hours for 7 to 10 days (Ref). May switch to oral antiviral after defervescence if no evidence of visceral involvement; continue until all lesions have crusted (Ref).
Uncomplicated infection: Oral: 800 mg 5 times daily for ≥5 to 7 days and until all lesions have crusted (Ref). In patients who are immunocompromised (eg, solid organ transplant recipients), some experts recommend a minimum duration of 7 days (Ref).
Varicella zoster virus, acute retinal necrosis (off-label use): IV: 10 mg/kg/dose every 8 hours for 10 to 14 days, followed by prolonged valacyclovir; in patients with HIV, intravitreal ganciclovir may be considered (Ref).
Varicella zoster virus, prevention in patients who are immunocompromised (off-label use):
Seropositive hematopoietic cell transplant recipients (allogeneic and autologous): Oral: 800 mg twice daily (Ref). Note: Initiate with the chemotherapeutic or conditioning regimen and continue for 1 year; may extend duration in patients requiring ongoing immunosuppression (some experts continue prophylaxis in these patients until 6 months after discontinuation of all systemic immunosuppression) (Ref).
Solid organ transplant recipients (patients who are VZV-seropositive who do not require CMV prophylaxis): Oral: 200 mg 3 to 5 times daily for 3 to 6 months after transplantation and during periods of lymphodepletion associated with treatment of rejection (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Note: Monitor closely for neurotoxicity (Ref). For usual recommended doses not described in the following sections, a comparable reduction in the dose and/or frequency may be considered based on CrCl or the type of dialysis, taking into consideration the goals of therapy and the anticipated duration of treatment (Ref).
Altered kidney function:
|
CrClb |
Oral |
IV | |||
|---|---|---|---|---|---|
|
If the usual dose is 400 mg every 12 hours |
If the usual dose is 200 mg 5 times daily |
If the usual dose is 800 mg 5 times daily |
If the usual dose is 5 mg/kg/dose every 8 hours |
If the usual dose is 10 mg/kg/dose every 8 hours | |
|
aRecommendations are from manufacturer’s labeling unless otherwise noted. bThe manufacturer's labeling dosing adjustments are reported as mL/minute/1.73 m2 based on data using CrCl adjusted for BSA (Blum 1982; de Miranda 1983). cWhile toxicity is not likely to occur with an unadjusted dose in patients with a CrCl of 10 to 25 mL/minute/1.73 m2 (as recommended in the manufacturer’s labeling), the exposure from the reduced dose is expected to be comparable to exposure achieved in patients receiving the usual recommended dose with normal kidney function (ie, CrCl >50 mL/minute/1.73 m2) (expert opinion). dManufacturer’s labeling recommends 800 mg every 12 hours. However, due to reports of neurotoxicity in patients with end-stage kidney disease (Almond 1995; Beales 1994; Davenport 1992), a reduced dose is preferred (expert opinion). | |||||
|
>50 mL/minute/1.73 m2 |
No dosage adjustment necessary. |
No dosage adjustment necessary. |
No dosage adjustment necessary. |
No dosage adjustment necessary. |
No dosage adjustment necessary. |
|
25 to 50 mL/minute/1.73 m2 |
No dosage adjustment necessary. |
No dosage adjustment necessary. |
No dosage adjustment necessary. |
5 mg/kg/dose every 12 hours |
10 mg/kg/dose every 12 hours |
|
10 to <25 mL/minute/1.73 m2 |
No dosage adjustment necessary or reduce to 200 mg every 12 hoursc |
No dosage adjustment necessary or reduce to 200 mg every 8 hoursc |
800 mg every 8 hours |
5 mg/kg/dose every 24 hours |
10 mg/kg/dose every 24 hours |
|
<10 mL/minute/1.73 m2 (not on dialysis) |
200 mg every 12 hours |
200 mg every 12 hours |
200 mg every 12 hours or 400 mg every 12 hours (severe infections)d |
2.5 mg/kg/dose every 24 hours |
5 mg/kg/dose every 24 hours |
Augmented renal clearance (measured urinary CrCl ≥130 mL/minute/1.73 m2): IV, Oral: Augmented renal clearance (ARC) is a condition that occurs in certain critically ill patients without organ dysfunction and with normal serum creatinine concentrations. Young patients (<55 years of age) admitted post trauma or major surgery are at highest risk for ARC, as well as those with sepsis, burns, or hematologic malignancies. An 8- to 24-hour measured urinary CrCl is necessary to identify these patients (Ref).
Use the indication-specific maximum allowable dose along with therapeutic drug monitoring when available (Ref).
Hemodialysis, intermittent (thrice weekly): Dialyzable (60% reduction following a 6-hour session (Ref)). Therapeutic drug monitoring of acyclovir is recommended when available (Ref).
Oral:
If the usual recommended dose is 200 mg 5 times daily or 400 mg every 12 hours: Administer 200 mg every 12 hours. Administer after dialysis when given on a dialysis day or administer an additional dose after each dialysis (Ref).
If the usual recommended dose is 800 mg 5 times daily: Administer a loading dose of 400 mg, followed by a maintenance dose of 200 mg every 12 hours, plus an additional 400 mg dose after each dialysis session (Ref). Note: Dose based on pharmacokinetic data and computer modeling.
IV: 2.5 to 5 mg/kg/dose every 24 hours. Administer after dialysis when given on a dialysis day (Ref). Note: Use the higher end of dosing range for viral meningoencephalitis and varicella-zoster infections.
Peritoneal dialysis: Dialyzable (12% reduction during continuous ambulatory peritoneal dialysis (Ref)): Therapeutic drug monitoring of acyclovir is recommended when available (Ref).
Oral:
If the usual recommended dose is 200 mg 5 times daily or 400 mg every 12 hours: Administer 200 mg every 12 hours (Ref).
If the usual recommended dose is 800 mg 5 times daily: Administer 600 to 800 mg every 24 hours (Ref).
IV: 2.5 to 5 mg/kg/dose every 24 hours, no supplemental dose needed (Ref). Note: Use the higher end of dosing range for viral meningoencephalitis and varicella-zoster infections.
CRRT: Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Recommendations are based on high-flux dialyzers and effluent flow rates of 20 to 25 mL/kg/hour (or ~1,500 to 3,000 mL/hour) unless otherwise noted. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important. Therapeutic drug monitoring of acyclovir is recommended when available (Ref).
IV: 5 to 10 mg/kg/dose every 12 to 24 hours (Ref). Note: Use the higher end of dosing range for viral meningoencephalitis and varicella-zoster infections.
PIRRT (eg, sustained, low-efficiency diafiltration): Drug clearance is dependent on the effluent flow rate, filter type, and method of renal replacement. Appropriate dosing requires consideration of adequate drug concentrations (eg, site of infection) and consideration of initial loading doses. Close monitoring of response and adverse reactions (eg, neurotoxicity) due to drug accumulation is important. Therapeutic drug monitoring of acyclovir is recommended when available (Ref).
IV: 5 to 10 mg/kg/dose every 12 to 24 hours (Ref). On non-PIRRT days, dose as for CrCl <10 mL/minute/1.73 m2. Note: Use the higher end of dosing range for viral meningoencephalitis and varicella-zoster infections.
Oral, IV: There are no dosage adjustments provided in the manufacturer's labeling; use caution in patients with severe impairment.
The recommendations for dosing in patients with obesity are based upon the best available evidence and clinical expertise. Senior Editorial Team: Jeffrey F. Barletta, PharmD, FCCM; Manjunath P. Pai, PharmD, FCP; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC.
Class 1, 2, or 3 obesity (BMI ≥30 kg/m2):
IV: Use ideal body weight (IBW) for weight-based dosing to avoid overdosing and subsequent toxicity (eg, acute renal failure). In patients with class 3 obesity (BMI ≥40 kg/m2) who are severely ill (eg, herpes simplex virus [HSV] encephalitis), consider using adjusted body weight for dose calculations (Ref).
Rationale for recommendations:
In patients with obesity, IBW has been used for weight-based dosing of acyclovir to avoid overdosing and subsequent toxicity (Ref). However, a pharmacokinetic study evaluating a single IBW-based dose of IV acyclovir in subjects with BMI ≥40 kg/m2 demonstrated lower systemic exposures compared to subjects who were not obese dosed using actual body weight (Ref). To avoid potentially underdosing severely ill patients (eg, HSV encephalitis) with class 3 obesity (eg, BMI ≥40 kg/m2), consider using adjusted body weight to calculate the weight-based IV dose (Ref), although this approach has not been evaluated in clinical outcome studies. Acyclovir is primarily excreted unchanged in urine, and careful attention to estimated kidney function is also essential in patients with obesity (Ref).
Refer to adult dosing; use with caution.
(For additional information see "Acyclovir (systemic): Pediatric drug information")
Cytomegalovirus (CMV) prophylaxis: Low-risk allogeneic hematopoietic stem cell transplant (HSCT) in seropositive recipient. Note: Begin at engraftment and continue to day 100; requires close monitoring for CMV reactivation (due to weak activity); not for use in patients at high risk for CMV disease (Ref):
Oral:
Infants, Children, and Adolescents <40 kg: 600 mg/m2/dose 4 times daily; maximum dose: 800 mg/dose.
Children and Adolescents ≥40 kg: 800 mg 4 times daily.
IV: Infants, Children, and Adolescents: 500 mg/m2/dose every 8 hours.
Varicella zoster virus, acute retinal necrosis, treatment, HIV-exposed/-infected:
Initial treatment: Note: Follow up IV therapy with oral valacyclovir or acyclovir therapy (valacyclovir preferred) (Ref).
Infants and Children: IV: 10 to 15 mg/kg/dose every 8 hours for 10 to 14 days (Ref).
Adolescents: IV: 10 mg/kg/dose every 8 hours for 10 to 14 days; recommended to be used in combination with 1 to 2 doses of intravitreal ganciclovir (Ref).
Maintenance treatment (alternative to valacyclovir): Infants and Children: Oral: 20 mg/kg/dose 4 times daily for 4 to 6 weeks to begin after 10- to 14-day course of IV acyclovir (Ref).
Herpes zoster (shingles), treatment:
Immunocompetent host:
Ambulatory therapy: Children ≥12 years and Adolescents: Oral: 800 mg every 4 hours (5 doses per day) for 5 to 7 days (Ref).
Hospitalized patient:
Infants and Children <2 years: IV: 10 mg/kg/dose every 8 hours for 7 to 10 days (Ref).
Children ≥2 years and Adolescents: IV: 500 mg/m2/dose every 8 hours for 7 to 10 days; some experts recommend 10 mg/kg/dose every 8 hours (Ref).
Immunocompromised host, non-HIV-exposed/-infected: IV: Infants, Children, and Adolescents: 10 mg/kg/dose every 8 hours for 7 to 10 days (Ref).
HIV-exposed/-infected:
Mild, uncomplicated disease and no or moderate immune suppression:
Infants and Children: Oral: 20 mg/kg/dose 4 times daily for 7 to 10 days; maximum dose: 800 mg/dose; consider longer course if resolution of lesions is slow (Ref).
Adolescents (alternative therapy): Oral: 800 mg 5 times daily for 7 to 10 days, longer if lesions resolve slowly (Ref).
Severe immune suppression or complicated disease; trigeminal nerve involvement, extensive multidermatomal zoster or extensive cutaneous lesions or visceral involvement:
Infants: IV: 10 mg/kg/dose every 8 hours until resolution of cutaneous lesions and visceral disease clearly begins, then convert to oral therapy to complete a 10- to 14-day total course of therapy (Ref).
Children: IV: 10 mg/kg/dose or 500 mg/m2/dose every 8 hours until resolution of cutaneous lesions and visceral disease clearly begins, then convert to oral therapy to complete a 10- to 14-day total course of therapy (Ref).
Adolescents: IV: 10 mg/kg/dose every 8 hours until clinical improvement is evident, then convert to oral therapy to complete a 10- to 14-day total course of therapy (Ref).
Herpes simplex virus (HSV) neonatal infection, treatment and suppressive therapy in very young infants (independent of HIV status):
Treatment (disseminated, CNS, or skin, eye, or mouth disease): Infants 1 to 3 months: IV: 20 mg/kg/dose every 8 hours; treatment duration: For cutaneous and mucous membrane infections (skin, eye, or mouth): 14 days; for CNS or disseminated infection: 21 days (Ref).
Chronic suppressive therapy following any neonatal HSV infection: Infants: Oral: 300 mg/m2/dose every 8 hours for 6 months; begin after completion of a 14- to 21-day-course of IV therapy dependent upon type of infection (Ref).
Herpes simplex virus encephalitis, treatment:
Independent of HIV status:
Infants and Children 3 months to <12 years: IV: 10 to 15 mg/kg/dose every 8 hours for 14 to 21 days. Note: Due to increased risk of neurotoxicity and nephrotoxicity, higher doses (20 mg/kg) are not routinely recommended (Ref).
Children ≥12 years and Adolescents: IV: 10 mg/kg/dose every 8 hours for 14 to 21 days (Ref).
Herpes simplex virus, genital infection:
First infection, mild to moderate:
Non-HIV-exposed/-infected:
Children <12 years: Oral: 40 to 80 mg/kg/day divided in 3 to 4 doses per day for 7 to 10 days; maximum daily dose: 1,200 mg/day (Ref).
Children and Adolescents ≥12 years: Oral: 200 mg every 4 hours while awake (5 times daily) or 400 mg 3 times daily for 7 to 10 days; treatment can be extended beyond 10 days if healing is not complete (Ref).
HIV-exposed/-infected:
Children: Oral: 20 mg/kg/dose 3 times daily for 7 to 10 days; maximum dose: 400 mg/dose (Ref).
Adolescents: Oral: 400 mg 3 times daily for 5 to 10 days (Ref).
First infection, severe (independent of HIV status): IV: Children and Adolescents ≥12 years: 5 mg/kg/dose every 8 hours for 5 to 7 days or 5 to 10 mg/kg/dose every 8 hours for 2 to 7 days, followed with oral therapy to complete at least 10 days of therapy (Ref).
Recurrent infection:
Children <12 years (independent of HIV status): Oral: 20 mg/kg/dose 3 times daily for 5 days; maximum dose: 400 mg/dose (Ref).
Children and Adolescents ≥12 years:
Non-HIV-exposed/-infected: Oral: 200 mg every 4 hours while awake (5 times daily) for 5 days, or 400 mg 3 times daily for 5 days, or 800 mg twice daily for 5 days or 800 mg 3 times daily for 2 days (Ref).
HIV-exposed/-infected: Adolescents: Oral: 400 mg 3 times daily for 5 to 10 days (Ref).
Suppression, chronic:
Non-HIV-exposed/-infected:
Children <12 years: Limited data available: Oral: 20 mg/kg/dose twice daily; maximum dose: 400 mg/dose (Ref).
Children and Adolescents ≥12 years: Oral: 400 mg twice daily; reassess therapy after 12 months (Ref).
HIV-exposed/-infected:
Infants and Children: Oral: 20 mg/kg/dose twice daily; maximum dose: 800 mg/dose (Ref).
Adolescents: Oral: 400 mg twice daily (Ref).
HSV orolabial disease (ie, gingivostomatitis, herpes labialis):
Non-HIV-exposed/-infected: Primary infection: Infants, Children, and Adolescents: Oral: 20 mg/kg/dose 4 times daily for 5 to 7 days; usual maximum dose: 800 mg/dose (Ref).
HIV-exposed/-infected (Ref):
Mild, symptomatic:
Infants and Children: Oral: 20 mg/kg/dose 4 times daily for 7 to 10 days; maximum dose: 400 mg/dose.
Adolescents: Oral: 400 mg 3 times daily for 5 to 10 days (Ref).
Moderate to severe, symptomatic: Note: Switch to oral therapy once lesions begin to regress and continue oral therapy until lesions completely healed.
Infants and Children: IV: 5 to 10 mg/kg/dose every 8 hours.
Adolescents: IV: 5 mg/kg/dose every 8 hours.
Herpes simplex virus, mucocutaneous infection:
Immunocompetent host: Infants, Children, and Adolescents:
Treatment:
IV: 5 mg/kg/dose every 8 hours (Ref).
Oral: 20 mg/kg/dose 4 times daily for 5 to 7 days; maximum dose: 800 mg/dose (Ref).
Suppression, chronic: Limited data available; no pediatric data; some experts recommend oral 20 mg/kg/dose 2 to 3 times daily for 6 to 12 months, then reevaluate need; maximum dose: 400 mg/dose (Ref).
Immunocompromised host:
Treatment:
IV:
Infants and Children: IV: 10 mg/kg/dose every 8 hours for 7 to 14 days (Ref).
Adolescents: IV: 5 to 10 mg/kg/dose every 8 hours; change to oral therapy after lesions begin to regress (Ref).
Oral: Children ≥2 years and Adolescents: 1,000 mg/day in 3 to 5 divided doses for 7 to 14 days (Ref).
Suppression, chronic (cutaneous, ocular) episodes:
Non-HIV-exposed/-infected:
Children ≥12 years and Adolescents: Oral: 400 mg twice daily; reassess at 12 months (Ref).
HIV-exposed/-infected:
Infants and Children: Oral: 20 mg/kg/dose twice daily; maximum dose: 800 mg/dose; reassess after 12 months (Ref).
Adolescents: Oral: 400 mg twice daily; reassess at 12 months (Ref).
HSV progressive or disseminated infection, treatment (immunocompromised host):
Non-HIV-exposed/-infected: Infants, Children, and Adolescents: IV: 10 mg/kg/dose every 8 hours for 7 to 14 days (Ref).
HIV-exposed/-infected: Infants, Children, and Adolescents: IV: 10 mg/kg/dose every 8 hours for 21 days; higher doses (up to 20 mg/kg/dose) may be used in children <12 years of age (Ref).
HSV, acute retinal necrosis, treatment, HIV-exposed/-infected: Infants and Children (Ref):
Initial treatment: IV: 10 to 15 mg/kg/dose every 8 hours for 10 to 14 days. Note: Follow up IV therapy with oral acyclovir or valacyclovir maintenance therapy.
Maintenance treatment (alternative to valacyclovir): Begin after 10- to 14-day course of IV acyclovir: Oral: 20 mg/kg/dose 4 times daily for 4 to 6 weeks.
HSV prophylaxis; immunocompromised hosts, seropositive:
HSCT in seropositive recipient (Ref):
Prevention of early reactivation: Note: Begin at conditioning and continue until engraftment or resolution of mucositis; whichever is longer (~30 days post-HSCT)
Infants, Children, and Adolescents <40 kg:
IV: 250 mg/m2/dose every 8 hours or 125 mg/m2/dose every 6 hours; maximum daily dose: 80 mg/kg/day
Oral: 60 to 90 mg/kg/day in 2 to 3 divided doses; maximum dose: 800 mg/dose twice daily
Children and Adolescents ≥40 kg:
IV: 250 mg/m2/dose every 12 hours
Oral: 400 to 800 mg twice daily
Prevention of late reactivation: Note: Treatment during first year after HSCT.
Infants, Children, and Adolescents <40 kg: Oral: 60 to 90 mg/kg/day in 2 to 3 divided doses; maximum daily dose: 800 mg twice daily
Children and Adolescents ≥40 kg: Oral: 800 mg twice daily
Other immunocompromised hosts who are HSV seropositive:
IV: Infants, Children, and Adolescents: 5 mg/kg/dose every 8 hours during period of risk (Ref).
Oral: Children ≥2 years and Adolescents: 200 mg every 4 hours while awake (5 doses daily) or 200 mg every 8 hours; administer during periods of risk (Ref).
Varicella (chickenpox) or herpes zoster (shingles), prophylaxis
HSCT: Prophylaxis of disease reactivation: Note: Continue therapy for 1 year after HSCT (Ref):
Infants, Children, and Adolescents <40 kg: Oral: 60 to 80 mg/kg/day in 2 to 3 divided doses
Children and Adolescents ≥40 kg: Oral: 800 mg twice daily
HIV-exposed/-infected: Limited data available: Note: Consider use if >96 hours postexposure or if VZV-immune globulin is not available; begin therapy 7 to 10 days after exposure; some experts begin therapy at first appearance of rash (Ref).
Infants and Children: Oral: 20 mg/kg/dose 4 times daily for 7 days; maximum dose: 800 mg/dose (Ref).
Adolescents: Oral: 800 mg 5 times daily for 5 to 7 days (Ref).
Other immunocompromised hosts: Infants, Children, and Adolescents: Oral: 20 mg/kg/dose 4 times daily for 7 days; maximum dose: 800 mg/dose. Note: Consider use if VZV-immune globulin or IVIG is not available; begin therapy 7 to 10 days after exposure (Ref).
Varicella (chickenpox), treatment: Begin treatment within the first 24 hours of rash onset:
Immunocompetent host:
Ambulatory therapy: Oral: Infants, Children, and Adolescents: 20 mg/kg/dose 4 times daily for 5 days; maximum daily dose: 3,200 mg/day (Ref).
Hospitalized patient: IV: Infants, Children, and Adolescents: 10 mg/kg/dose or 500 mg/m2/dose every 8 hours for 7 to 14 days (Ref); some experts recommend 15 to 20 mg/kg/dose for severe disseminated or CNS infection (Ref).
Immunocompromised host, non-HIV-exposed/-infected:
Infants and Children <2 years: IV: 10 mg/kg/dose every 8 hours; duration dependent upon clinical response, typically 7 to 14 days (Ref).
Children ≥2 years and Adolescents: IV: 500 mg/m2/dose every 8 hours duration dependent upon clinical response, typically 7 to 14 days; some experts recommend 10 mg/kg/dose every 8 hours (Ref).
HIV-exposed/-infected:
Mild, uncomplicated disease and no or moderate immune suppression:
Infants and Children: Oral: 20 mg/kg/dose 4 times daily for 7 to 10 days and until no new lesions for 48 hours; maximum dose: 800 mg/dose (Ref).
Adolescents (alternative therapy): Oral: 800 mg 5 times daily for 5 to 7 days (Ref).
Severe, complicated disease or severe immune suppression:
Infants: IV: 10 mg/kg/dose every 8 hours for 7 to 10 days and until no new lesions for 48 hours (Ref).
Children: IV: 10 mg/kg/dose or 500 mg/m2/dose every 8 hours for 7 to 10 days or until no new lesions for 48 hours (Ref).
Adolescents: IV: 10 mg/kg/dose every 8 hours for 7 to 10 days; may convert to oral therapy after defervescence and if no evidence of visceral involvement is evident (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Monitor closely for neurotoxicity (Ref).
Infants, Children and Adolescents: IV:
CrCl >50 mL/minute/1.73 m2: No dosage adjustment necessary
CrCl 25 to 50 mL/minute/1.73 m2: Administer the usual recommended dose every 12 hours
CrCl 10 to <25 mL/minute/1.73 m2: Administer the usual recommended dose every 24 hours
CrCl <10 mL/minute/1.73 m2: Administer 50% of the usual recommended dose every 24 hours (eg, if the usual recommended dose is 10 mg/kg/dose every 8 hours, then administer 5 mg/kg/dose every 24 hours)
Intermittent hemodialysis (IHD): Dialyzable (60% reduction following a 6-hour session): 5 mg/kg/dose every 24 hours; administer after hemodialysis on dialysis days (Ref)
Peritoneal dialysis (PD): 5 mg/kg/dose every 24 hours; no supplemental dose needed (Ref)
Continuous renal replacement therapy (CRRT): 10 mg/kg/dose every 12 hours (Ref)
There are no dosage adjustments provided in the manufacturer's labeling.
Acyclovir may cause acute kidney injury, resulting most often from obstructive nephropathy but may also be due to interstitial nephritis or renal tubular necrosis in adult and pediatric patients (Ref). Kidney injury is reversible in most cases after dosage reduction or discontinuation; however, some cases may not return to baseline (Ref).
Mechanism: Dose-related; not clearly established, multiple proposed mechanisms. Usually attributed to the formation of acyclovir crystals, which result in intrarenal obstruction and nephropathy (Ref). May also be due to glomerular hyperfiltration; injury may occur because kidneys have little reserve, resulting in an intolerance to nephrotoxic insult or increased filtrate delivery to the renal tubules (Ref). Other proposed mechanisms include an immune reaction that may contribute to interstitial nephritis and a major metabolite of acyclovir (9-carboxymethoxymethylguanine [CMMG]) that may be directly cytotoxic to cells of the renal tubule (Ref).
Onset: Varied; most commonly occurred within 3 days of initiation in adult and pediatric patients, but has also been reported later in therapy (Ref).
Risk factors:
Adult patients:
• Rapid infusion of high dose (Ref)
• Intravenous administration (due to higher bioavailability of acyclovir/valacyclovir); although cases during oral therapy have been reported (Ref)
• Volume depletion (Ref)
• Preexisting kidney impairment (Ref)
• Hypertension (Ref)
• Diabetes (Ref)
• Concurrent use of nephrotoxic agents (eg, nonsteroidal anti-inflammatory drugs, vancomycin) (Ref)
Pediatric patients:
• Doses >500 mg/m2 (Ref)
• Doses >15 mg/kg (associated with a 25% to 49% reduction in eGFR) (Ref)
• Age >8 years (Ref)
• Weight >20 kg (Ref)
• BMI >19 kg/m2 (Ref)
• Concurrent ceftriaxone with or without gadolinium (Ref)
• Concurrent use of nephrotoxic agents (Ref)
• Glomerular hyperfiltration (Ref)
Acyclovir-induced neurotoxicity most commonly includes reported symptoms such as agitation, confusion, dysarthria, hallucination, and impaired consciousness (Ref). Other reported symptoms include aphasia, ataxia, myoclonus, tremor, and seizure (including status epilepticus) (Ref). Most cases of neurotoxicity are reversible after discontinuation with or without hemodialysis; however, some cases may not be fully reversible (Ref).
Mechanism: Dose-related; indirect, via metabolite 9-carboxymethoxymethylguanine accumulation (Ref).
Onset: Rapid; typically reported within 3 days of initiation (Ref).
Risk factors:
• Higher doses (Ref)
• Kidney impairment (Ref); however, some cases have been reported in normal kidney function (Ref)
• Advanced age (Ref)
• Damage to the blood-brain barrier (Ref)
Thrombotic thrombocytopenic purpura (TTP) and hemolytic-uremic syndrome (HUS), manifestations of thrombotic microangiopathy, have been reported with both acyclovir and valacyclovir (Ref). TTP/HUS may result in damage to the brain, heart, kidney, liver, and pancreas (Ref). Resolution has been reported with discontinuation and appropriate therapy (Ref).
Mechanism: Idiosyncratic; thrombotic microangiopathy (and resulting TTP and HUS) involves endothelial cell injury, intravascular platelet-fibrin thrombi, and vascular damage (Ref).
Onset: Varied; has been reported within 3 days of initiation (Ref) and after 1 year of therapy (case with valacyclovir) (Ref).
Risk factors (largely unknown):
• Genetic susceptibility may play a role for drug-induced HUS (Ref)
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. As reported with IV administration, unless otherwise noted.
>10%:
Hematologic & oncologic: Decrease in absolute neutrophil count (neonates: 3% to 16%), decreased hemoglobin (neonates: 13%)
Nervous system: Malaise (oral: 12%)
1% to 10%:
Dermatologic: Pruritus (≤2%), skin rash (≤2%), urticaria (≤2%)
Gastrointestinal: Diarrhea (oral: 2% to 3%; IV: <1%), nausea (oral and IV: ≤7%), vomiting (oral and IV: ≤7%)
Hematologic & oncologic: Thrombocytopenia (neonates: 5% to 10%; children, adolescents, and adults: <1%)
Hepatic: Increased serum bilirubin (neonates, grades 3/4: 4%), increased serum transaminases (1% to 2%)
Local: Inflammation at injection site (≤9%), injection-site phlebitis (≤9%)
Nervous system: Headache (≤2%)
Renal: Increased blood urea nitrogen (5% to 10%), increased serum creatinine (5% to 10%)
<1%: Hematologic & oncologic: Anemia, leukocytosis, neutropenia, neutrophilia, thrombocytosis
Frequency not defined: Gastrointestinal: Anorexia
Postmarketing:
Cardiovascular: Hypotension, peripheral edema
Dermatologic: Acute generalized exanthematous pustulosis (Kubin 2016), alopecia (Sharma 2016), bullous rash (Gurkan 2012), contact dermatitis (topical) (Vernassiere 2003), erythema multiforme, fixed drug eruption (Lee 2016), skin photosensitivity (topical) (Rodriguez-Serna 1999), Stevens-Johnson syndrome (Sen 2020), toxic epidermal necrolysis (Sen 2020)
Genitourinary: Hematuria (Meng 2011)
Hematologic & oncologic: Disseminated intravascular coagulation, hemolysis, hemolytic-uremic syndrome (Bell 1997), leukopenia, lymphadenopathy, thrombotic microangiopathy (Goli 2017), thrombotic thrombocytopenic purpura (Bell 1997)
Hepatic: Hepatitis, hyperbilirubinemia, jaundice
Hypersensitivity: Anaphylaxis, angioedema (Jen 2011), hypersensitivity angiitis
Nervous system: Aggressive behavior, agitation (Brandariz-Nuñez 2021), aphasia (Patel 2019), ataxia (Patel 2019), coma, confusion (Brandariz-Nuñez 2021), delirium (Rashiq 1993), dizziness, drowsiness, dysarthria (Brandariz-Nuñez 2021), encephalopathy, fatigue, hallucination (Brandariz-Nuñez 2021), impaired consciousness (Brandariz-Nuñez 2021), myoclonus (Umoru 2020), obtundation (Marks 2020), pain, paresthesia, psychosis, seizure (Hoskote 2016), tremor (Patel 2019)
Neuromuscular & skeletal: Myalgia
Renal: Acute kidney injury (Lee 2018), interstitial nephritis (Pańczyk-Tomaszewska 2020), kidney disease (obstructive nephropathy) (Fleischer 2010), renal tubular necrosis (Chávez-Iñiguez 2018)
Miscellaneous: Fever
Hypersensitivity to acyclovir, valacyclovir, or any component of the formulation
Concerns related to adverse effects:
• Extravasation: Acyclovir IV is an irritant (depending on concentration); avoid extravasation.
Disease-related concerns:
• Varicella: Appropriate use: For maximum benefit, treatment should begin within 24 hours of appearance of rash; oral route not recommended for routine use in otherwise healthy children with varicella but may be effective in patients at increased risk of moderate to severe infection (>12 years of age, chronic cutaneous or pulmonary disorders, long-term salicylate therapy, corticosteroid therapy).
Dosage form specific issues:
• Injection: Use IV preparation with caution in patients with underlying neurologic abnormalities, serious hepatic or electrolyte abnormalities, or substantial hypoxia. Encephalopathic changes characterized by lethargy, obtundation, confusion, hallucination, tremors, agitation, seizure, or coma have been observed in patients receiving IV acyclovir.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Oral:
Generic: 200 mg
Solution, Intravenous, as sodium [strength expressed as base]:
Generic: 50 mg/mL (20 mL [DSC])
Solution, Intravenous, as sodium [strength expressed as base, preservative free]:
Generic: 50 mg/mL (10 mL, 20 mL)
Suspension, Oral:
Zovirax: 200 mg/5 mL (473 mL [DSC]) [contains methylparaben, propylparaben; banana flavor]
Generic: 200 mg/5 mL (473 mL)
Tablet, Oral:
Zovirax: 400 mg [DSC]
Zovirax: 800 mg [DSC] [contains fd&c blue #2 (indigotine,indigo carmine)]
Generic: 400 mg, 800 mg
Yes
Capsules (Acyclovir Oral)
200 mg (per each): $0.13 - $1.53
Solution (Acyclovir Sodium Intravenous)
50 mg/mL (per mL): $0.52 - $2.26
Suspension (Acyclovir Oral)
200 mg/5 mL (per mL): $0.94 - $1.27
Tablets (Acyclovir Oral)
400 mg (per each): $0.21 - $2.17
800 mg (per each): $0.36 - $4.22
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Intravenous:
Generic: 25 mg/mL (20 mL)
Solution, Intravenous, as sodium [strength expressed as base]:
Generic: 50 mg/mL (10 mL, 20 mL)
Suspension, Oral:
Zovirax: 200 mg/5 mL (125 mL) [contains methylparaben, propylparaben]
Tablet, Oral:
Generic: 200 mg, 400 mg, 800 mg
Oral: Administer with or without food.
IV: Avoid rapid infusion; infuse over 1 hour to prevent renal damage; maintain adequate hydration of patient; check for phlebitis and rotate infusion sites. Do not administer IM or SUBQ.
May be an irritant with vesicant-like properties; ensure proper needle or catheter placement prior to and during IV infusion. Avoid extravasation.
Extravasation management : If extravasation occurs, stop infusion immediately; leave needle/cannula in place temporarily but do NOT flush the line; gently aspirate extravasated solution, then remove needle/cannula; elevate extremity; apply dry warm compresses; initiate hyaluronidase antidote for refractory cases in addition to supportive management (Ref).
Hyaluronidase: Intradermal or SUBQ: Inject a total of 1 mL (15 units/mL) as 5 separate 0.2 mL injections (using a tuberculin syringe) around the site of extravasation; if IV catheter remains in place, administer IV through the infiltrated catheter; may repeat in 30 to 60 minutes if no resolution (Ref).
Oral: May administer with or without food; shake suspension well before use. Maintain adequate hydration during therapy.
Parenteral: Administer by slow IV infusion over at least 1 hour; rapid infusion is associated with nephrotoxicity due to crystalluria and renal tubular damage and should be avoided. Maintain adequate hydration during therapy. Do not administer IV push, IM, or SUBQ.
Acyclovir IV may be an irritant with vesicant-like properties; ensure proper needle or catheter placement prior to and during IV infusion; avoid extravasation. If extravasation occurs, stop infusion immediately; leave cannula/needle in place temporarily but do NOT flush the line; gently aspirate extravasated solution, then remove needle/cannula; elevate extremity; apply dry warm compresses; initiate hyaluronidase antidote in addition to supportive management for refractory cases (Ref).
Oral:
Herpes simplex virus (HSV), genital: Treatment of initial episodes and the management of recurrent episodes of genital herpes.
Herpes zoster (shingles): Acute treatment of herpes zoster (shingles).
Varicella (chickenpox): Treatment of varicella (chickenpox).
Injection:
Herpes simplex encephalitis: Treatment of herpes simplex encephalitis.
Herpes simplex virus (HSV), genital infection (severe): Treatment of severe initial clinical episodes of genital herpes in patients who are immunocompetent.
Herpes simplex virus (HSV), mucocutaneous infection in patients who are immunocompromised: Treatment of initial and recurrent mucosal and cutaneous herpes simplex (HSV-1 and HSV-2) in patients who are immunocompromised.
Herpes simplex virus (HSV), neonatal: Treatment of neonatal herpes infections.
Herpes zoster (shingles) in patients who are immunocompromised: Treatment of herpes zoster (shingles) in patients who are immunocompromised.
Bell palsy, new onset; Cytomegalovirus prevention in low-risk allogeneic hematopoietic cell transplant recipients; Herpes simplex virus, esophagitis; Herpes simplex virus, prevention in patients who are immunocompromised; Varicella zoster virus, acute retinal necrosis; Varicella zoster virus, encephalitis; Varicella zoster virus, prevention in patients who are immunocompromised
Acyclovir may be confused with famciclovir, ganciclovir, Retrovir, valacyclovir, valganciclovir
Zovirax may be confused with Doribax, Valtrex, Zithromax, Zostrix, Zyloprim, Zyvox
Substrate of OAT1/3, OCT1; Inhibits CYP1A2 (weak)
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. Risk X: Avoid combination
CloZAPine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of CloZAPine. Risk C: Monitor therapy
Fezolinetant: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Fezolinetant. Risk X: Avoid combination
Foscarnet: May enhance the nephrotoxic effect of Acyclovir-Valacyclovir. Risk X: Avoid combination
Mycophenolate: Acyclovir-Valacyclovir may increase the serum concentration of Mycophenolate. Mycophenolate may increase the serum concentration of Acyclovir-Valacyclovir. Risk C: Monitor therapy
Netilmicin (Systemic): Acyclovir (Systemic) may enhance the nephrotoxic effect of Netilmicin (Systemic). Acyclovir (Systemic) may enhance the neurotoxic effect of Netilmicin (Systemic). Risk X: Avoid combination
Talimogene Laherparepvec: Antiherpetic Antivirals may diminish the therapeutic effect of Talimogene Laherparepvec. Risk C: Monitor therapy
Tenofovir Products: Acyclovir-Valacyclovir may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Acyclovir-Valacyclovir. Risk C: Monitor therapy
Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy
TiZANidine: CYP1A2 Inhibitors (Weak) may increase the serum concentration of TiZANidine. Management: Avoid these combinations when possible. If combined use is necessary, initiate tizanidine at an adult dose of 2 mg and increase in 2 to 4 mg increments based on patient response. Monitor for increased effects of tizanidine, including adverse reactions. Risk D: Consider therapy modification
Varicella Virus Vaccine: Acyclovir-Valacyclovir may diminish the therapeutic effect of Varicella Virus Vaccine. Management: When possible, avoid use of acyclovir or valacyclovir within the 24 hours prior to administration of the varicella vaccine, and avoid use of these antiviral agents for 14 days after vaccination. Risk X: Avoid combination
Zoster Vaccine (Live/Attenuated): Acyclovir-Valacyclovir may diminish the therapeutic effect of Zoster Vaccine (Live/Attenuated). Risk X: Avoid combination
Acyclovir crosses the placenta (Frenkel 1991; Henderson 1992; Kimberlin 1998).
A pregnancy registry established in 1984 and closed in 1999 included 749 pregnancies with 756 known outcomes following first trimester acyclovir exposure. Data from the registry did not find an increase in the number of birth defects with exposure to acyclovir when compared to those expected in the general population. In addition, no pattern of birth defects was observed (Stone 2004). A population-based registry study conducted in Denmark had similar results. The study used data from 1996 to 2008 and included 1,561 pregnancies with first trimester acyclovir exposure; an increased risk of birth defects was not observed (Pasternak 2010). One study observed an increased risk of gastroschisis following use of antiherpetic medications such as acyclovir during the first trimester to treat maternal genital herpes; this risk was also increased in offspring of women with genital herpes not receiving treatment (Ahrens 2013).
Due to pregnancy-induced physiologic changes, the pharmacokinetic properties of acyclovir may be altered in some women (Brocklehurst 1998; Frenkel 1991; Kimberlin 1998; Leung 2009). Dose adjustments are required for suppressive therapy and recurrent infections during pregnancy due to increased renal clearance (ACOG 2020). Acyclovir is associated with adverse effects on renal function; this risk may be increased with IV administration to patients during the third trimester of pregnancy (Boujenah 2020).
Acyclovir is recommended for the treatment of genital herpes simplex virus (HSV) in pregnant patients (ACOG 2020; CDC [Workowski 2021]). Primary HSV infection during the first trimester may be associated with neonatal chorioretinitis, microcephaly, and skin lesions. The risk of perinatal transmission is greater when the primary infection occurs during pregnancy. Maternal treatment decreases duration and severity of disease and duration of viral shedding (ACOG 2020). Suppressive therapy is recommended for patients beginning at 36 weeks' gestation who have a history of genital lesions (ACOG 2020; CDC [Workowski 2021]).
Acyclovir is also recommended for the treatment of varicella (chickenpox) in pregnant patients. When treatment is started within 24 hours of rash development, acyclovir reduces the duration and total number of maternal lesions; however, it does not prevent congenital varicella syndrome (ACOG 2015).
Acyclovir is present in breast milk.
Information related to the presence of acyclovir in breast milk is available from multiple sources:
• Acyclovir use for the treatment of labial herpes simplex in a lactating patient 6 weeks postpartum was described in a case report. Acyclovir 900 mg IV was administered daily for 5 days and breast milk was sampled every 6 hours after the last dose. The maximum breast milk concentration was 7.3 mcg/mL observed within the first 72 hours of sampling (Bork 1995). Using a milk concentration of 7.3 mcg/mL, the relative infant dose (RID) of acyclovir is 1.83% to 3.65% compared to an IV infant therapeutic dose of 30 to 60 mg/kg/day, providing an estimated infant dose via breast milk of 1.095 mg/kg/day. In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).
• The mean half-life of acyclovir in breast milk was 3.2 hours in one study (Lau 1987).
• Low/negligible concentrations of acyclovir appear in breast milk for up to 5 days after the last maternal dose (Bork 1995; Frenkel 1991).
In one case report, the mother reported no adverse events in her exclusively breastfed infant following a maternal dose of acyclovir 800 mg orally 5 times daily for 7 days (Taddio 1994). Acyclovir has been detected in the urine of breastfeeding infants (Frenkel 1991; Lau 1987).
Although the manufacturer recommends that caution be exercised when administering acyclovir to patients who are breastfeeding, acyclovir is considered compatible with breastfeeding (ACOG 2020; WHO 2002). Patients with HSV infection taking acyclovir may breastfeed as long as there are not lesions on the breast, body lesions are covered, and strict hand hygiene is practiced; patients with herpetic lesions near or on the breast should not breastfeed (ACOG 2020). Patients with breast lesions can pump and discard milk to maintain milk supply until lesions are healed and breastfeeding can be resumed (D’Andrea 2019).
Some products may contain sodium.
Hydration status, urinalysis, BUN, serum creatinine, urine output; liver enzymes, CBC; signs and symptoms of neurotoxicity, monitor for nephrotoxicity in pediatric patients when using high-dose therapy; neutrophil count at least twice weekly in neonates receiving acyclovir 60 mg/kg/day IV. Monitor infusion site.
Acyclovir is converted to acyclovir monophosphate by virus-specific thymidine kinase then further converted to acyclovir triphosphate by other cellular enzymes. Acyclovir triphosphate inhibits DNA synthesis and viral replication by competing with deoxyguanosine triphosphate for viral DNA polymerase and being incorporated into viral DNA.
Absorption: Oral: Poorly absorbed; absorption improves with multiple small doses compared to one large daily dose (de Miranda 1983).
Distribution: Widely (eg, brain, kidney, lungs, liver, spleen, muscle, uterus, vagina, CSF) (de Miranda 1983; Laskin 1983); CSF acyclovir concentration is ~50% of plasma concentrations.
Vd:
Neonates (Sampson 2014; manufacturer's labeling):
PMA <30 weeks: Median: 2.88 L/kg (range: 0.646 to 5.3 L/kg).
PMA 30 to <36 weeks: Median: 4.49 L/kg (range: 1.87 to 10.85 L/kg).
PMA 36 to 41 weeks: Median: 2.55 L/kg (range: 0.293 to 4.09 L/kg).
Infants <3 months: 1.08 ± 0.35 L/kg (manufacturer's labeling).
Infants ≥3 months and Children: 1.01 ± 0.28 L/kg (manufacturer's labeling).
Adults: 0.8 ± 0.18 L/kg (Spector 1981).
Protein binding: 9% to 33%.
Metabolism: Converted by viral enzymes to acyclovir monophosphate, and further converted to diphosphate then triphosphate (active form) by cellular enzymes.
Bioavailability: Oral: 10% to 20% with normal renal function (bioavailability decreases with increased dose).
Half-life elimination:
Neonates (Sampson 2014):
PMA <30 weeks: Median: 10.2 hours (range: 4.73 to 13.2 hours).
PMA 30 to 35 weeks: Median: 6.55 hours (range: 4.28 to 9.26 hours).
PMA 36 to 41 weeks: Median: 3 hours (range: 1.61 to 3.69 hours).
Infants ≤3 months: 3.8 ± 1.19 hours (manufacturer's labeling).
Infants >3 months and Children: 2.36 ± 0.97 hours (manufacturer's labeling).
Adults: ~2.5 hours (with normal renal function); 20 hours (ESRD) (Gorlitsky 2017); Hemodialysis: ~5 hours.
Excretion: Urine (62% to 91% as unchanged drug and metabolite).
Altered kidney function: Total body clearance and half-life are dependent on renal function.
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