Acyclovir (Systemic)

Pharmacologic Category

Antiviral Agent

Dosing: Adult

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 (AAN [Gronseth 2012]; AAO-HNSF [Baugh 2013]; Ronthal 2018); some experts only recommend addition of an antiviral to steroid therapy in patients with severe Bell palsy (de Almeida 2014).

Cytomegalovirus (CMV), prevention in low-risk allogeneic hematopoietic cell transplant (HCT) recipients (alternative agent) (off-label use): 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 (ASBMT/IDSA [Tomblyn 2009]):

IV: 500 mg/m2/dose every 8 hours for up to 4 weeks or until hospital discharge, followed by oral therapy (ASBMT/IDSA [Tomblyn 2009]; Boeckh 2009; Ljungman 2002)

Oral: Following initial IV therapy: 800 mg 4 times daily (ASBMT/IDSA [Tomblyn 2009]; Boeckh 2009; Ljungman 2002)

Herpes simplex virus (HSV), 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 HSV therapy should be initiated in all patients with suspected encephalitis (IDSA [Tunkel 2008]; Tunkel 2018; Wilck 2013).

Herpes simplex virus, mucocutaneous infection:

Esophagitis (off-label use):

Immunocompetent patients: Oral: 400 mg 3 times daily or 200 mg 5 times daily for 7 to 10 days (Bonis 2018; Canalejo Castrillero 2010)

Immunocompromised patients: Oral: 400 mg 5 times daily for 14 to 21 days (Bonis 2018)

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 (Bonis 2018; Canalejo Castrillero 2010).

Genital:

Immunocompetent patients:

Treatment, initial episode:

Oral: 400 mg 3 times daily or 200 mg 5 times daily for 7 to 10 days; extend duration if lesions have not healed completely after 10 days (CDC [Workowski 2015]).

IV (for severe disease): 5 to 10 mg/kg/dose every 8 hours for 2 to 7 days, followed by oral acyclovir (or similar antiviral) to complete ≥10 days of therapy total (CDC [Workowski 2015])

Treatment, recurrent episode: Oral: 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. Note: Treatment is most effective when initiated during the prodrome or within 1 day of lesion onset (CDC [Workowski 2015]).

Suppressive therapy (eg, for severe and/or frequent recurrences): Oral: 400 mg twice daily. Note: Reassess need periodically (eg, annually) (CDC [Workowski 2015]).

Immunocompromised patients (including HIV-infected):

Treatment, initial or recurrent episode:

Oral: 400 mg 3 times daily for 5 to 10 days; extend treatment duration if lesions have not healed completely after 10 days (CDC [Workowski 2015]; HHS [OI adult 2018]; Wilck 2013).

IV (for severe disease): 5 to 10 mg/kg/dose every 8 hours for 2 to 7 days, followed by oral acyclovir (or similar antiviral) once lesions begin to regress and continue for ≥10 days of therapy and until complete resolution (CDC [Workowski 2015]; HHS [OI adult 2018]).

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) (CDC [Workowski 2015]; HHS [OI adult 2018]).

Pregnant females:

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 (ACOG 2007).

Treatment, recurrent episode (symptomatic): Oral: 400 mg 3 times daily or 800 mg twice daily for 5 days (ACOG 2007). Note: Some experts reserve treatment of recurrent episodes for patients with severe and/or frequent symptoms (Riley 2018).

Suppressive therapy, for patients with a genital HSV lesion anytime during pregnancy: Oral: 400 mg 3 times daily, beginning at 36 weeks' gestation and continued until the onset of labor (ACOG 2007; CDC [Workowski 2015]; Riley 2018). Note: Some experts offer suppressive therapy earlier than 36 weeks' gestation for women who have a first-episode lesion during the third trimester (Riley 2018).

Orolabial: Note: Initiate therapy at earliest symptom.

Immunocompetent and immunocompromised patients (including HIV-infected):

Treatment, initial or recurrent episode:

Oral: 400 mg 3 times daily for 5 to 10 days and until complete lesion resolution in immunocompromised patients (HHS [OI adult 2018]; Klein 2018; Wilck 2013)

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 (HHS [OI adult 2018]; Wilck 2013).

Suppressive therapy (eg, for severe and/or frequent recurrences): Oral: 400 mg twice daily (HHS [OI adult 2018]; Rooney 1993). Note: Reassess need periodically (eg, annually) (HHS [adult OI 2018]).

Herpes simplex virus, prevention in immunocompromised patients (off-label use):

Seropositive HCT recipients (allogeneic or autologous) or seropositive patients undergoing leukemia induction chemotherapy:

IV: 250 mg/m2/dose every 12 hours (ASBMT/IDSA [Tomblyn 2009])

Oral: 400 to 800 mg twice daily (ASBMT/IDSA [Tomblyn 2009])

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 (ASBMT/IDSA [Tomblyn 2009]; ASCO/IDSA [Taplitz 2018]).

Solid organ transplant recipients (HSV-seropositive patients who do not require CMV prophylaxis): Oral: 400 to 800 mg twice daily for ≥1 month (Wilck 2013); some experts recommend continuing for 3 to 6 months after transplantation and during periods of lymphodepletion associated with treatment of rejection (Fishman 2018).

Herpes zoster (shingles), treatment:

Immunocompetent patients: Oral: 800 mg 5 times daily for 7 days (Pott Junior 2018; Shafran 2004). Initiate at earliest sign or symptom; treatment is most effective when initiated ≤72 hours after rash onset, but may initiate treatment >72 hours after rash onset if new lesions are continuing to appear (Cohen 1999).

Immunocompromised patients (including HIV-infected):

Acute localized dermatomal: Oral: 800 mg 5 times daily for 7 to 10 days; consider longer duration if lesions resolve slowly (HHS [OI adult 2018]; Pergam 2013).

Extensive cutaneous lesions or visceral involvement: IV: 10 to 15 mg/kg/dose every 8 hours (HHS [OI adult 2018]; Pergam 2013). 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 (HHS [OI adult 2018]).

Herpes zoster ophthalmicus (off-label use): Immunocompromised patients or patients who require hospitalization for sight-threatening disease: IV: 10 mg/kg/dose every 8 hours for 7 days (Albrecht 2018a)

Varicella (chickenpox), treatment: Ideally initiate therapy within 24 hours of symptom onset, but may start later if the patient still has active lesions:

Immunocompetent patients with uncomplicated infection: Oral: 800 mg 5 times daily for ≥5 to 7 days and until all lesions have crusted (Albrecht 2018b; Arvin 1996; Wallace 1992)

Immunocompromised patients (including HIV-infected):

Severe or complicated infection: IV: 10 mg/kg/dose every 8 hours for 7 to 10 days (HHS [OI adult 2018]; Pergam 2013); some experts recommend up to 15 mg/kg/dose every 8 hours (HHS [OI adult 2018]). May switch to oral antiviral after defervescence if no evidence of visceral involvement; continue until all lesions have crusted (HHS [OI adult 2018]; Pergam 2013).

Uncomplicated infection: Oral: 800 mg 5 times daily for 5 to 7 days (HHS [OI adult 2018]); some experts recommend a minimum duration of 7 days, extending the course until all lesions have crusted (Albrecht 2018b; Pergam 2013).

Varicella zoster virus (VZV), acute retinal necrosis (off-label use): IV: 10 to 15 mg/kg/dose every 8 hours for 10 to 14 days, followed by ~6 weeks of valacyclovir (Albrecht 2018a; HHS [OI adult 2018]); in HIV-infected patients, intravitreal ganciclovir should be added (HHS [OI adult 2018]).

Varicella zoster virus, encephalitis (off-label use): IV: 10 to 15 mg/kg/dose every 8 hours for 10 to 14 days (IDSA [Tunkel 2008])

Varicella zoster virus, prevention in immunocompromised patients (off-label use):

Seropositive HCT recipients (allogeneic and autologous): Oral: 800 mg twice daily (ASBMT/IDSA [Tomblyn 2009]; Boeckh 2006). 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) (ASBMT/IDSA [Tomblyn 2009]).

Solid organ transplant recipients (VZV-seropositive patients 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 (Fishman 2018; Pergam 2013)

* See Dosage and Administration in AHFS Essentials for additional information.

Dosing: Geriatric

Refer to adult dosing; use with caution.

Dosing: Renal Impairment: Adult

Note: Monitor closely for neurotoxicity (Chowdhury 2016)

Note: The 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).

Oral:

CrCl >25 mL/minute/1.73 m2: No dosage adjustment necessary.

CrCl 10 to 25 mL/minute/1.73 m2: If the usual recommended dose is 800 mg 5 times daily: Administer 800 mg every 8 hours

CrCl <10 mL/minute/1.73 m2:

If the usual recommended dose is 200 mg 5 times daily or 400 mg every 12 hours: Administer 200 mg every 12 hours

If the usual recommended dose is 800 mg 5 times daily: Administer 200 mg every 12 hours (IDSA [Gupta 2005])

Intermittent hemodialysis (IHD): Dialyzable (60% reduction following a 6-hour session):

Note: Dosing dependent on the assumption of 3-times-weekly, complete IHD sessions. Administer after hemodialysis on dialysis days.

If the usual recommended dose is 200 mg 5 times daily or 400 mg every 12 hours: Administer 200 mg every 12 hours

If the usual recommended dose is 800 mg 5 times daily: Administer a loading dose of 400 mg and a maintenance dose of 200 mg twice daily plus a single 400 mg dose after each dialysis (Almond 1995). Note: Dose based on pharmacokinetic data and computer modeling.

Continuous ambulatory peritoneal dialysis (CAPD): 600 to 800 mg daily (Stathoulopoulou 1996)

IV:

If the usual recommended dose is 10 mg/kg/dose every 8 hours:

CrCl >50 mL/minute/1.73 m2: No dosage adjustment necessary.

CrCl 25 to 50 mL/minute/1.73 m2: 10 mg/kg/dose every 12 hours

CrCl 10 to <25 mL/minute/1.73 m2: 10 mg/kg/dose every 24 hours

CrCl <10 mL/minute/1.73 m2: 5 mg/kg/dose every 24 hours

If the usual recommended dose is 5 mg/kg/dose every 8 hours:

CrCl >50 mL/minute/1.73 m2: No dosage adjustment necessary.

CrCl 25 to 50 mL/minute/1.73 m2: 5 mg/kg/dose every 12 hours

CrCl 10 to <25 mL/minute/1.73 m2: 5 mg/kg/dose every 24 hours

CrCl <10 mL/minute/1.73 m2: 2.5 mg/kg/dose every 24 hours

Intermittent hemodialysis (IHD): Dialyzable (60% reduction following a 6-hour session): 2.5 to 5 mg/kg/dose every 24 hours (Heintz 2009). Note: Use higher end of dosing range for viral meningoencephalitis and varicella-zoster infections. Dosing dependent on the assumption of 3-times-weekly, complete IHD sessions. Administer after hemodialysis on dialysis days

Peritoneal dialysis (PD): 2.5 to 5 mg/kg/dose every 24 hours; no supplemental dose needed (Aronoff 2007). Note: Use higher end of dosing range for viral meningoencephalitis and varicella-zoster infections.

Continuous renal replacement therapy (CRRT) (Heintz 2009): Drug clearance is highly dependent on the method of renal replacement, filter type, and flow rate. Appropriate dosing requires close monitoring of pharmacologic response, signs of adverse reactions due to drug accumulation, as well as drug concentrations in relation to target trough (if appropriate). The following are general recommendations only (based on dialysate flow/ultrafiltration rates of 1 to 2 L/hour and minimal residual renal function) and should not supersede clinical judgment:

CVVH: 5 to 10 mg/kg/dose every 24 hours

CVVHD/CVVHDF: 5 to 10 mg/kg/dose every 12 to 24 hours

Note: The higher end of dosage range is recommended for viral meningoencephalitis and varicella-zoster virus infections.

Dosing: Hepatic Impairment: Adult

Oral, IV: There are no dosage adjustments provided in the manufacturer's labeling; use caution in patients with severe impairment.

Dosing: Obesity: Adult

IV: In obese patients, acyclovir IV has been dosed using ideal body weight (IBW) to avoid overdosing and subsequent toxicity. However, in a pharmacokinetic study using a single acyclovir IV dose, morbidly obese patients (BMI ≥ 40 kg/m2) dosed using IBW had lower systemic exposures compared to normal weight subjects dosed using actual body weight (exposure based on AUC, Cmax, and T > IC50 [time the drug concentration remains above the 50% inhibitory concentration]) (Turner 2016). Therefore, to avoid potentially underdosing obese patients who are severely ill (eg, HSV encephalitis), some clinicians use adjusted body weight (AjBW) to determine the IV dose (AjBW=IBW + [0.4 x (actual body weight-IBW)]) (Wong 2017), although this approach has not been evaluated in clinical studies.

Dosing: Pediatric

Note: Obese patients should be dosed using ideal body weight. Parenteral IV doses >15 mg/kg/dose or 500 mg/m2 may be associated with an increased risk of nephrotoxicity; close monitoring of renal function is recommended (Rao 2015).

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 (Tomblyn 2009):

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

Herpes zoster, acute retinal necrosis, treatment (HIV-exposed/-positive):

Initial treatment: IV: Note: Follow up IV therapy with oral acyclovir or valacyclovir maintenance therapy.

Infants: 10 to 15 mg/kg/dose every 8 hours for 10 to 14 days (DHHS [pediatric] 2013)

Children: 10 to 15 mg/kg/dose every 8 hours for 10 to 14 days (DHHS [pediatric] 2013)

Adolescents: 10 to 15 mg/kg/dose every 8 hours for 10 to 14 days (DHHS [adult] 2015)

Maintenance treatment; begin after 10- to 14-day course of IV acyclovir: Oral: Infants and Children: 20 mg/kg/dose 4 times daily for 4 to 6 weeks (DHHS [pediatric] 2013)

Herpes zoster (shingles), treatment:

Immunocompetent host:

Ambulatory therapy: Oral: Children ≥12 years and Adolescents: 800 mg every 4 hours (5 doses per day) for 5 to 7 days (Red Book [AAP 2015])

Hospitalized patient: IV:

Infants: 10 mg/kg/dose every 8 hours for 7 to 10 days (Red Book [AAP 2015])

Children and Adolescents: 500 mg/m2/dose every 8 hours for 7 to 10 days; some experts recommend 10 mg/kg/dose every 8 hours (Red Book [AAP 2015])

Immunocompromised host (non-HIV-exposed/-positive): IV: Infants, Children, and Adolescents: 10 mg/kg/dose every 8 hours for 7 to 10 days (Red Book [AAP 2015])

HIV-exposed/-positive:

Mild, uncomplicated disease and no or moderate immune suppression: Oral:

Infants and Children: 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 (DHHS [pediatric] 2013)

Adolescents: 800 mg 5 times daily for 7 to 10 days, longer if lesions resolve slowly (DHHS [adult] 2015)

Severe immune suppression or complicated disease; trigeminal nerve involvement, extensive multidermatomal zoster or extensive cutaneous lesions or visceral involvement: IV:

Infants: 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 (DHHS [pediatric] 2013)

Children: 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 (DHHS [pediatric] 2013)

Adolescents: 10 to 15 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 (DHHS [adult] 2015)

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 (AAP [Kimberlin 2013]; Bradley 2015; CDC [Workowski 2015]; DHHS [pediatric] 2013; Red Book [AAP 2015])

Chronic suppressive therapy following any neonatal HSV infection:

AAP Recommendation (low dose, 6-month course): 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 (AAP [Kimberlin 2013]; Kimberlin 2011; Red Book [AAP 2015])

Alternate dosing (high dose, 2-year course) in infants with disseminated or CNS infection (Tiffany 2005): Limited data available: Infants and Children <3 years: Oral: Begin after completion of a 21-day course of IV therapy; dosing based on a prospective trial of 16 consecutive neonates (GA: Premature: n=4; term=12; age at treatment: Neonate: n=14; PNA >30 days: n=1) following disseminated or CNS infection; pharmacokinetic data were used to determine dosing regimen to maintain serum acyclovir concentration above target of 2 to 3 mcg/mL; treatment was continued for 2 years in 14 of 16 patients; results showed normal neurodevelopmental outcomes in 69% and normal motor development in 70%; no untoward effects were reported during the study duration.

Initial dosing: 400 mg twice daily; approximate dose: 1,200 to 1,600 mg/m2/dose twice daily

Maintenance dosing: Note: Approximate doses for patients born at term:

Infants 1 to <5 months: 400 mg twice daily

Infants 5 to <9 months: 600 mg twice daily

Infants and Children 9 to <15 months: 800 mg twice daily

Children 15 to 24 months: 1,000 mg twice daily

Note: In the trial, serum acyclovir concentrations were evaluated to assess adequacy of dosing to maintain serum concentrations above the target of 2 to 3 mcg/mL. Samples were collected 1 hour after a witnessed dose; if the acyclovir serum concentration approached or was below the target, the dose was increased to the next greater 200 mg increment. Maximum dose: 1,200 mg. Serum concentrations were evaluated every 3 months; in order to limit the phlebotomy losses, follow-up serum concentrations were not evaluated outside of routine monitoring.

HSV encephalitis, treatment:

Infants and Children 3 months to <12 years:

Non-HIV-exposed/-positive: 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 recommended (Red Book [AAP 2015]).

HIV-exposed/-positive: IV: 10 mg/kg/dose every 8 hours for 21 days; higher doses (up to 20 mg/kg) may be necessary (DHHS [pediatric] 2013)

Children ≥12 years and Adolescents (independent of HIV status): IV: 10 mg/kg/dose every 8 hours for 14 to 21 days (Red Book [AAP 2015)]

HSV genital infection:

First infection, mild to moderate:

Non-HIV-exposed/-positive:

Children <12 years: Oral: 40 to 80 mg/kg/day divided in 3 to 4 doses per day for 5 to 10 days; maximum daily dose: 1,200 mg/day (Bradley 2015; Red Book [AAP 2015])

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 (CDC [Workowski 2015]; Red Book [AAP 2015])

HIV-exposed/-positive:

Children: Oral: 20 mg/kg/dose 3 times daily for 7 to 10 days; maximum dose: 400 mg/dose (DHHS [pediatric] 2013)

Adolescents: Oral: 400 mg 3 times daily for 5 to 14 days (DHHS [adult] 2015)

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 (CDC [Workowski 2015]; Red Book [AAP 2015])

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 (Bradley 2015; DHHS [pediatric] 2013)

Children and Adolescents ≥12 years:

Non-HIV-exposed/-positive: 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 (CDC [Workowski 2015]; Red Book [AAP 2015])

HIV-exposed/-positive: Adolescents: Oral: 400 mg 3 times daily for 5 to 14 days (DHHS [adult] 2015)

Suppression, chronic:

Non-HIV-exposed/-positive:

Children <12 years: Limited data available: Oral: 20 mg/kg/dose twice daily; maximum dose: 400 mg/dose (Bradley 2015)

Children and Adolescents ≥12 years: Oral: 400 mg twice daily; reassess therapy after 12 months (CDC [Workowski 2015]; Red Book [AAP 2015])

HIV-exposed/-positive:

Infants and Children: Oral: 20 mg/kg/dose twice daily; maximum dose: 800 mg/dose (DHHS [pediatric] 2013)

Adolescents: Oral: 400 mg twice daily (DHHS [adult] 2015)

HSV gingivostomatitis:

Non-HIV-exposed/-positive: Primary infection:

AAP recommendations: Children and Adolescents: Oral: 20 mg/kg/dose 4 times daily for 5 to 7 days; usual maximum dose: 200 mg/dose, others have reported higher (400 mg/dose) (Bradley 2015; Cernik 2008; Red Book [AAP 2015])

Alternate dosing: Infants ≥10 months, Children, and Adolescents: Oral: 15 mg/kg/dose five times daily for 7 days; maximum dose: 200 mg/dose (Amir 1997; Balfour 1999); dosing based on a placebo controlled trial in children 1 to 6 years of age (n=72, treatment group: n=31); results showed when treatment started within 72 hours of symptom onset a shorter duration of symptoms and viral shedding was observed (Amir 1997)

HIV-exposed/-positive (DHHS [pediatric] 2013):

Mild, symptomatic: Oral: Infants and Children: 20 mg/kg/dose 4 times daily for 7 to 10 days; maximum dose: 400 mg/dose

Moderate to severe, symptomatic: IV: Infants and Children: 5 to 10 mg/kg/dose every 8 hours; switch to oral therapy once lesions begin to regress

HSV, herpes labialis (cold sore) (HIV-exposed/-positive): Treatment:

Infants and Children: Oral: 20 mg/kg/dose 4 times daily for 5 days; maximum dose: 400 mg/dose (DHHS [pediatric] 2013)

Adolescents: Oral: 400 mg 3 times daily for 5 to 10 days (DHHS [adult] 2015)

HSV, herpes labialis (cold sore) recurrent, chronic suppressive therapy: Immunocompetent Children and Adolescents: Oral: 10 mg/kg/dose 3 times daily; maximum daily dose: 1,000 mg/day; reevaluate after 12 months (Red Book [AAP 2015])

HSV mucocutaneous infection:

Immunocompetent host: Infants, Children, and Adolescents:

Treatment (Bradley 2015):

IV: 5 mg/kg/dose every 8 hours

Oral: 20 mg/kg/dose 4 times daily for 5 to 7 days; maximum dose: 800 mg/dose

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 (Bradley 2015)

Immunocompromised host:

Treatment:

IV:

Infants and Children: 10 mg/kg/dose every 8 hours for 7 to 14 days (Red Book [AAP 2015])

Adolescents: 5 to 10 mg/kg/dose every 8 hours; change to oral therapy after lesions begin to regress (DHHS [adult] 2015; Red Book [AAP 2015])

Oral: Children ≥2 years and Adolescents: 1,000 mg/day in 3 to 5 divided doses for 7 to 14 days; some suggest the maximum daily dose should not exceed 80 mg/kg/day (Red Book 2009; Red Book [AAP 2015])

Suppression, chronic (cutaneous, ocular) episodes:

Infants and Children (HIV-exposed/-positive): Oral: 20 mg/kg/dose twice daily; maximum dose: 800 mg/dose; reassess after 12 months (DHHS [pediatric] 2013)

Children 12 years of age (non-HIV-exposed/-positive): Prevention of ocular episodes: Oral: 400 mg twice daily; reassess at 12 months (Red Book [AAP 2015])

Adolescents (independent of HIV status): Oral: 400 mg twice daily; reassess at 12 months (DHHS [adult] 2015; Red Book [AAP 2015])

HSV progressive or disseminated infection, treatment (immunocompromised host):

Non-HIV-exposed/-positive: Infants, Children, and Adolescents: IV: 10 mg/kg/dose every 8 hours for 7 to 14 days (Red Book [AAP 2015])

HIV-exposed/-positive: 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 (DHHS [pediatric] 2013; Red Book [AAP 2015])

HSV, acute retinal necrosis, treatment (HIV-exposed/-positive): Children (DHHS [pediatric] 2013):

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: 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:

Hematopoietic stem cell transplant (HSCT) in seropositive recipient (Tomblyn 2009):

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 (Red Book [AAP 2015])

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 (Red Book [AAP 2015])

Varicella (chickenpox) or Herpes zoster (shingles), prophylaxis

Hematopoietic stem cell transplant (HSCT): Prophylaxis of disease reactivation: Note: Continue therapy for 1 year after HSCT (Tomblyn 2009):

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/-positive: 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 (DHHS [pediatric] 2013).

Infants and Children: Oral: 20 mg/kg/dose 4 times daily for 7 days; maximum dose: 800 mg/dose (DHHS [pediatric] 2013)

Adolescents: Oral: 800 mg 5 times daily for 5 to 7 days (DHHS [adult] 2015)

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 (Red Book [AAP] 2015).

Varicella (chickenpox), treatment: Begin treatment within the first 24 hours of rash onset:

Immunocompetent host:

Ambulatory therapy: Oral: Children ≥2 years and Adolescents: 20 mg/kg/dose 4 times daily for 5 days; maximum daily dose: 3,200 mg/day (Red Book [AAP 2015])

Hospitalized patient: IV: Infants, Children, and Adolescents: 10 mg/kg/dose or 500 mg/m2/dose every 8 hours for 7 to 14 days (Bradley 2015; Red Book [AAP 2015]); some experts recommend 15 to 20 mg/kg/dose for severe disseminated or CNS infection (Bradley 2015)

Immunocompromised host (non-HIV-exposed/-positive): IV:

Infants: 10 mg/kg/dose every 8 hours for 7 to 10 days (Red Book [AAP 2015])

Children and Adolescents: 500 mg/m2/dose every 8 hours for 7 to 10 days; some experts recommend 10 mg/kg/dose every 8 hours (Red Book [AAP 2015])

HIV-exposed/-positive:

Mild, uncomplicated disease and no or moderate immune suppression: Oral:

Infants and Children: 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 (DHHS [pediatric] 2013)

Adolescents: 800 mg 5 times daily for 5 to 7 days (DHHS [adult] 2015)

Severe, complicated disease or severe immune suppression: IV:

Infants: 10 mg/kg/dose every 8 hours for 7 to 10 days and until no new lesions for 48 hours (DHHS [pediatric] 2013)

Children: 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 (DHHS [pediatric] 2013)

Adolescents: 10 to 15 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 (DHHS [adult] 2015)

Dosing: Renal Impairment: Pediatric

Monitor closely for neurotoxicity (Chowdhury 2016).

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 (Aronoff 2007)

Peritoneal dialysis (PD): 5 mg/kg/dose every 24 hours; no supplemental dose needed (Aronoff 2007)

Continuous renal replacement therapy (CRRT): 10 mg/kg/dose every 12 hours (Aronoff 2007)

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Calculations

• Body Surface Area (Du Bois Method)
• Body Surface Area (Gehan & George Method)
• Body Surface Area (Mosteller Method)
• Creatinine Clearance by Cockcroft-Gault
• Creatinine Clearance by Cockcroft-Gault (SI units)
• Creatinine Clearance by Cockcroft-Gault with IBW
• Creatinine Clearance by Cockcroft-Gault with IBW (SI units)
• Creatinine Clearance by Jelliffe
• Creatinine Clearance by Sanaka
• Glomerular Filtration Rate by Abbreviated MDRD
• Glomerular Filtration Rate by Abbreviated MDRD (SI units)
• Glomerular Filtration Rate by MDRD
• Glomerular Filtration Rate by MDRD (IDMS-Traceable SCr)
• Glomerular Filtration Rate by MDRD (SI units)
• Glomerular Filtration Rate by Schwartz
• Glomerular Filtration Rate Estimate in African Americans by AASK Equation
• Ideal Body Weight and Dosing Weight
• Ideal Body Weight Percentage
• Ideal Body Weight: Pediatrics

Use: Labeled Indications

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 immunocompetent patients.

Herpes simplex virus (HSV), mucocutaneous infection in immunocompromised patients: Treatment of initial and recurrent mucosal and cutaneous herpes simplex (HSV-1 and HSV-2) in immunocompromised patients.

Herpes simplex virus (HSV), neonatal: Treatment of neonatal herpes infections.

Herpes zoster (shingles) in immunocompromised patients: Treatment of herpes zoster (shingles) in immunocompromised patients.

* See Uses in AHFS Essentials for additional information.

Use: Off-Label: Adult

Bell palsy, new onsetLevel of Evidence [B, G]

There is insufficient evidence to recommend acyclovir for the treatment of Bell palsy. However, American Academy of Neurology (AAN) guidelines state that antivirals may, at best, provide a modest increase in recovery and may be reserved as an option. Access Full Off-Label Monograph

Cytomegalovirus prevention in low-risk allogeneic hematopoietic cell transplant recipientsLevel of Evidence [G]

Based on the American Society for Blood and Marrow Transplantation (ASBMT) and Infectious Diseases Society of America (IDSA) guidelines for preventing infectious complications among hematopoietic cell transplant recipients, acyclovir is recommended as an alternative agent to prevent cytomegalovirus (CMV) reactivation in low-risk allogeneic hematopoietic cell transplant (HCT) recipients.

Herpes simplex virus, esophagitisLevel of Evidence [C]

Clinical experience and case reports suggest the utility of acyclovir in the treatment of esophagitis due to herpes simplex virus (HSV) in immunocompetent or immunocompromised patients Ref.

Herpes simplex virus, prevention in immunocompromised patientsLevel of Evidence [C, G]

Based on the ASBMT/IDSA guidelines for preventing infectious complications among hematopoietic cell transplant recipients, acyclovir is an effective and recommended agent to prevent HSV reactivation (early and late) in HCT recipients.

Based on the American Society of Clinical Oncology (ASCO) and IDSA guidelines for antimicrobial prophylaxis for adult patients with cancer-related immunosuppression, acyclovir is an effective and recommended agent to prevent HSV reactivation in patients undergoing leukemia induction therapy.

Clinical experience suggests the utility of acyclovir for prevention of HSV in seropositive solid organ transplant recipients who are not already receiving CMV prophylaxis Ref.

Herpes zoster ophthalmicusLevel of Evidence [C]

Clinical experience suggests the utility of IV acyclovir for the treatment of herpes zoster ophthalmicus in patients who are immunocompromised or require hospitalization for sight-threatening disease Ref.

Varicella zoster virus, acute retinal necrosisLevel of Evidence [C, G]

Based on the US Department of Health and Human Services (HHS) guidelines for the prevention and treatment of opportunistic infections in HIV-infected adults and adolescents, intravenous acyclovir is an effective and recommended agent in the management of varicella zoster virus (VZV) acute retinal necrosis (ARN) in immunocompromised patients (HIV-infected patients).

Clinical experience suggests the utility of intravenous acyclovir in the treatment of VZV ARN in immunocompetent patients Ref.

Varicella zoster virus, encephalitisLevel of Evidence [C, G]

Based on the IDSA clinical practice guideline for the management of encephalitis, intravenous acyclovir is recommended for the treatment of encephalitis caused by VZV.

Clinical experience suggests the use of intravenous acyclovir for the treatment of VZV encephalitis Ref.

Varicella zoster virus, prevention in immunocompromised patientsLevel of Evidence [C, G]

Based on the ASBMT/IDSA guidelines for preventing infectious complications among hematopoietic cell transplant recipients, acyclovir is an effective and recommended agent to prevent VZV reactivation in HCT recipients (allogeneic and autologous) who are VZV seropositive.

Clinical experience suggests the utility of acyclovir for the prevention of VZV in seropositive solid organ transplant recipients who are not already receiving CMV prophylaxis Ref.

Level of Evidence Definitions

Level of Evidence Scale

Clinical Practice Guidelines

Oncology:

CIBMTR, “Guidelines for Preventing Infectious Complications among Hematopoietic Cell Transplant Recipients: A Global Perspective,” October 2009

IDSA, "Clinical Practice Guideline for the Use of Antimicrobial Agents in Neutropenic Patients with Cancer: 2010 Update,” 2011

National Comprehensive Cancer Network® (NCCN), "NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®),” Prevention and Treatment of Cancer-Related Infections

Opportunistic Infection:

HHS, Guidelines for the Prevention and Treatment of Opportunistic Infections in HIV-Infected Adults and Adolescents

Sexually Transmitted Disease:

CDC, “Sexually Transmitted Diseases Treatment Guidelines,” June 2015.

Public Health Agency of Canada, “Canadian Guidelines on Sexually Transmitted Infections," January 2010

Skin and Soft-tissue Infection:

IDSA, “Practice Guidelines for the Diagnosis and Management of Skin and Soft Tissue Infections,” June 2014

Administration: IV

For IV infusion only. 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. Acyclovir IV is an irritant (depending on concentration); avoid extravasation.

Administration: Injectable Detail

pH: 10.5 to 11.6 (reconstituted solution)

Administration: Oral

Administer with or without food.

Administration: Pediatric

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 is an irritant (depending on concentration); avoid extravasation. If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Apply dry warm compresses. Intradermal hyaluronidase may be considered for refractory cases (Reynolds 2014).

Vesicant/Extravasation Risk

Irritant at concentrations >7 mg/mL

Dietary Considerations

Some products may contain sodium.

Storage/Stability

Capsule, oral suspension, tablet: Store at controlled room temperature of 15°C to 25°C (59°F to 77°F); protect capsule and tablet from moisture.

Powder for injection: Store undiluted vials at 15°C to 25°C (59°F to 77°F). Following reconstitution (final concentration 50 mg/mL), solution is stable for 12 hours at room temperature.

Solution for injection: Store solution at 20°C to 25°C (68°F to 77°F).

Do not refrigerate reconstituted solutions or solutions diluted for infusion as they may precipitate. Once diluted for infusion with NS or D5W, use within 24 hours.

Preparation for Administration: Adult

Powder for injection: Reconstitute acyclovir 500 mg powder with SWFI 10 mL (final concentration 50 mg/mL); do not use bacteriostatic water containing benzyl alcohol or parabens.

For intravenous infusion, dilute reconstituted powder for injection or solution for injection in D5W or NS to a final concentration ≤7 mg/mL. Concentrations >10 mg/mL increase the risk of phlebitis.

Preparation for Administration: Pediatric

Parenteral: Reconstitute vial for injection to 50 mg/mL with SWFI; do not use bacteriostatic water containing benzyl alcohol or parabens. For intravenous infusion, dilute in D5W, D5NS, D51/4NS, D51/2NS, LR, or NS to a final concentration ≤7 mg/mL. In fluid restricted patients, concentrations up to 10 mg/mL have been infused; concentrations >10 mg/mL increase the risk of phlebitis.

Compatibility

See Trissel’s IV Compatibility Database

Open Trissel's IV Compatibility

Medication Patient Education with HCAHPS Considerations

What is this drug used for?

• It is used to treat herpes infections.

• It is used to treat shingles.

• It is used to treat chickenpox.

• It may be given to you for other reasons. Talk with the doctor.

Frequently reported side effects of this drug

• Nausea

• Vomiting

• Loss of strength and energy

• Injection site irritation

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Behavioral changes

• Mood changes

• Confusion

• Sensing things that seem real but are not

• Seizures

• Tremors

• Kidney problems like unable to pass urine, blood in the urine, change in amount of urine passed, or weight gain.

• Thrombotic thrombocytopenic purpura/hemolytic uremic syndrome like bruising or bleeding; severe loss of strength and energy; dark urine or yellow skin; pale skin; change in the amount of urine passed; vision changes; change in strength on one side is greater than the other; difficulty speaking or thinking; change in balance; or fever.

• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.

Medication Safety Issues

Sound-alike/look-alike issues:

Contraindications

Hypersensitivity to acyclovir, valacyclovir, or any component of the formulation

Warnings/Precautions

Concerns related to adverse effects:

• CNS effects: Neurotoxicity (eg, tremor/myoclonus, confusion, agitation, lethargy, hallucination, impaired consciousness) has been reported; risk may be increased with higher doses and in patients with renal failure. Monitor patients for signs/symptoms of neurotoxicity; ensure appropriate dosage reductions in patients with renal impairment (Chowdhury 2016).

• Extravasation: Acyclovir IV is an irritant (depending on concentration); avoid extravasation.

• Renal effects: Renal failure (sometimes fatal) has been reported. Dehydration, preexisting renal disease, and nephrotoxic drugs increase risk; ensure patient is adequately hydrated during oral or IV therapy.

• Thrombotic microangiopathy: Has been reported in immunocompromised patients receiving acyclovir.

Disease-related concerns:

• Renal impairment: Use with caution; dosage adjustment recommended. Neurotoxicity may be more common in patients with renal impairment (Chowdhury 2016).

• 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).

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

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.

Other warnings/precautions:

• Adequate hydration: Maintain adequate hydration during oral or IV therapy.

* See Cautions in AHFS Essentials for additional information.

Geriatric Considerations

For herpes zoster, acyclovir should be started within 72 hours of the appearance of the rash to be effective. Older adults may be more prone to the central nervous system disturbances (eg, sedation, confusion) and dizziness potentially caused by acyclovir. Dose adjustment may be necessary depending on creatinine clearance.

Warnings: Additional Pediatric Considerations

Acyclovir can cause intrarenal obstructive nephropathy, interstitial nephritis, and tubular necrosis resulting in significant renal insufficiency. In one study, 35% (131/373 courses) in 371 pediatric patients treated with IV acyclovir mostly for meningoencephalitis were observed to have renal dysfunction. Renal dysfunction typically occurred within 48 hours of initiation and was reversible in most cases after dosage reduction or discontinuation, although in some instances, return to baseline was not observed. Analysis of the degree of dysfunction based on percent reduction of estimated GFR (eGFR) showed that of the 373 acyclovir courses, 22% (81/373) had an eGFR reduction of 25% to 49%, renal injury (defined as a 50% to 75% reduction in eGFR) in 9.7% (36/373), and renal failure (eGFR reduction >75%) in 3.8% (14/373). Doses >500 mg/m2 were significantly associated with all levels of nephrotoxicity and acyclovir doses >15 mg/kg were significantly associated with a 25% to 49% reduction in eGFR. Statistically significant risk factors for renal failure identified through univariate analysis were age >8 years, weight >20 kg, BMI >19 kg/m2, and concurrent ceftriaxone with or without gadolinium. Associations of other antibiotics and contrast agents were not statistically significant. Monitor renal function during therapy, particularly for high doses and in older pediatric patients (>8 years). Outside of the neonatal period, reduced dosing or use of mg/m2 dosing in larger children may need to be considered; further studies are necessary (Rao 2015).

Pregnancy Considerations

Acyclovir has been shown to cross the human placenta (Henderson 1992).

Results from a pregnancy registry, established in 1984 and closed in 1999, did not find an increase in the number of birth defects with exposure to acyclovir when compared to those expected in the general population. However, due to the small size of the registry and lack of long-term data, the manufacturer recommends using during pregnancy with caution and only when clearly needed. Acyclovir is recommended for the treatment of genital herpes in pregnant patients (ACOG 2007; CDC [Workowski 2015]).

Breast-Feeding Considerations

Acyclovir is present in breast milk.

The relative infant dose (RID) of acyclovir is 1.83% to 3.65% when calculated using the highest breast milk concentration located and compared to an IV infant therapeutic dose of 30 to 60 mg/kg/day.

In general, breastfeeding is considered acceptable when the RID of a medication is <10% (Anderson 2016; Ito 2000).

The RID of acyclovir was calculated using a milk concentration of 7.3 mcg/mL, providing an estimated daily infant dose via breast milk of 1.095 mg/kg/day. This milk concentration was obtained following maternal administration acyclovir 900 mg IV daily for 5 days (Bork 1995). The mean half-life of acyclovir in breast milk was 3.2 hours in one study (Lau 1987); acyclovir was measurable in breast milk for up to 88 hours after the last maternal dose in another (Bork 1995). Acyclovir has been detected in the urine of a breastfeeding infant (Lau 1987).

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 is considered compatible with breastfeeding (WHO 2002). Acyclovir may be used for the treatment of genital herpes in breastfeeding women (ACOG 2007; CDC [Workowski 2015]). The manufacturer recommends that caution be exercised when administering acyclovir to breastfeeding women. Breastfeeding mothers with herpetic lesions near or on the breast should avoid breastfeeding (Gartner 2005); precautions should be taken to prevent infant contact with active lesions (ACOG 2007).

Briggs' Drugs in Pregnancy & Lactation

• Acyclovir

Adverse Reactions

As reported with IV administration, unless otherwise noted.

>10%:

Central nervous system: Malaise (oral: 12%)

Hematologic & oncologic: Decrease in absolute neutrophil count (neonates: 3% to 16%), decreased hemoglobin (neonates: 13%)

1% to 10%:

Central nervous system: Headache (oral: ≤2%)

Dermatologic: Pruritus (2%), skin rash (2%), urticaria (2%)

Gastrointestinal: Nausea (oral and IV: ≤7%), vomiting (oral and IV: ≤7%), diarrhea (oral: 2% to 3%; IV: <1%)

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%)

Renal: Increased blood urea nitrogen (5% to 10%), increased serum creatinine (5% to 10%)

<1%, postmarketing, and/or case reports (all routes): Abdominal pain, aggressive behavior, agitation, alopecia, anaphylaxis, anemia, angioedema, anorexia, ataxia, coma, confusion, delirium, disseminated intravascular coagulation, dizziness, drowsiness, dysarthria, encephalopathy, erythema multiforme, fatigue, fever, gastrointestinal distress, hallucination, hematuria, hemolysis, hepatitis, hyperbilirubinemia, hypersensitivity angiitis, hypotension, impaired consciousness, increased liver enzymes, jaundice, leukocytosis, leukopenia, lymphadenopathy, myalgia, neutropenia, neutrophilia, obtundation, pain, paresthesia, peripheral edema, psychosis, renal failure syndrome, renal pain, seizure, skin photosensitivity, Stevens-Johnson syndrome, thrombocythemia, toxic epidermal necrolysis, tremor, visual disturbance

* See Cautions in AHFS Essentials for additional information.

Allergy and Idiosyncratic Reactions

• Antiviral Acyclic Guanine Derivative Allergy

Metabolism/Transport Effects

Inhibits CYP1A2 (weak)

Drug Interactions Open Interactions

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. Management: Drugs listed as exceptions to this monograph are discussed in further detail in separate drug interaction monographs. Risk C: Monitor therapy

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

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. Exceptions: Dyphylline. 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

Zidovudine: Acyclovir-Valacyclovir may enhance the CNS depressant effect of Zidovudine. Risk C: Monitor therapy

Zoster Vaccine (Live/Attenuated): Acyclovir-Valacyclovir may diminish the therapeutic effect of Zoster Vaccine (Live/Attenuated). Risk X: Avoid combination

Monitoring Parameters

Urinalysis, BUN, serum creatinine, urine output; liver enzymes, CBC; monitor for neurotoxicity and 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.

Advanced Practitioners Physical Assessment/Monitoring

Obtain urinalysis, BUN, serum creatinine, CBC, and liver function tests. Dosage adjustment may be needed with renal impairment. Assess for effectiveness of therapy.

Nursing Physical Assessment/Monitoring

Check ordered labs and report abnormalities. Monitor for effectiveness of therapy.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Capsule, Oral:

Zovirax: 200 mg [DSC] [contains fd&c blue #2 (indigotine), parabens]

Generic: 200 mg

Solution, Intravenous, as sodium [strength expressed as base]:

Generic: 50 mg/mL (20 mL)

Solution, Intravenous, as sodium [strength expressed as base, preservative free]:

Generic: 50 mg/mL (10 mL, 20 mL)

Solution Reconstituted, Intravenous, as sodium [strength expressed as base]:

Generic: 500 mg (1 ea [DSC])

Suspension, Oral:

Zovirax: 200 mg/5 mL (473 mL) [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)]

Generic: 400 mg, 800 mg

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Intravenous:

Generic: 25 mg/mL (20 mL)

Solution, Intravenous, as sodium [strength expressed as base]:

Generic: 50 mg/mL (10 mL, 20 mL)

Solution Reconstituted, Intravenous, as sodium [strength expressed as base]:

Generic: 500 mg ([DSC])

Suspension, Oral:

Zovirax: 200 mg/5 mL (125 mL) [contains methylparaben, propylparaben]

Tablet, Oral:

Generic: 200 mg, 400 mg, 800 mg

Anatomic Therapeutic Chemical (ATC) Classification

• J05AB01

Generic Available (US)

Yes

Pricing: US

Capsules (Acyclovir Oral)

200 mg (per each): $0.13 - $2.92

Solution (Acyclovir Sodium Intravenous)

50 mg/mL (per mL): $0.52 - $2.26

Suspension (Acyclovir Oral)

200 mg/5 mL (per mL): $0.90 - $0.94

Suspension (Zovirax Oral)

200 mg/5 mL (per mL): $1.24

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.

Mechanism of Action

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.

Pharmacodynamics/Kinetics

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.

Vdss (Blum 1982; Laskin 1983; Spector 1981):

Neonates to 3 months of age: 28.8 L/1.73 m2

Children 1 to 2 years: 31.6 L/1.73 m2

Children 2 to 7 years: 42 L/1.73 m2

Adults: 0.8 L/kg (63.6 L)

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: Terminal: Neonates and Infants ≤3 months: 3.8 ± 1.19 hours; Infants >3 months to Children ≤12 years: 2.36 ± 0.97 hours; 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)

Pharmacodynamics/Kinetics: Additional Considerations

Renal function impairment: Total body clearance and half-life are dependent on renal function.

Dental Use

Treatment of initial and prophylaxis of recurrent mucosal and cutaneous herpes simplex (HSV-1 and HSV-2) infections in immunocompromised patients

* See Uses in AHFS Essentials for additional information.

Local Anesthetic/Vasoconstrictor Precautions

No information available to require special precautions

Dental Health Professional Considerations

Although some conflicting data, dental treatment may be a risk factor for asymptomatic viral shedding of herpes simplex virus type-1 (HSV-1) into human saliva in patients with previous exposure to the virus (Hyland 2007).

It is recommended to reappoint the patient if an active lesion is present. If the lesion is already "crusted" over, treatment will not induce spread of the virus but treatment is aimed at patient comfort during the procedure relating to the wound healing on their lip.

Effects on Dental Treatment

No significant effects or complications reported (see Dental Health Professional Considerations)

Effects on Bleeding

No information available to require special precautions

Dental Usual Dosing

Mucocutaneous HSV: Adults:

Immunocompromised (off-label use): Oral: 400 mg 5 times a day for 7-14 days

Chronic suppression of recurrent herpes labialis (cold sores) (off-label use): Immunocompetent adults: oral: 400 mg twice daily (Rooney 1993)

Related Information

• Dosing Considerations for the Critically Ill Patient With Morbid Obesity
• Management of Drug Extravasations
• Oral Medications That Should Not Be Crushed or Altered

Index Terms

Aciclovir; ACV; Acycloguanosine; Acyclovir Sodium; Zovirax

FDA Approval Date

May 29, 1982

References

ACOG Committee on Practice Bulletins. ACOG Practice Bulletin. Clinical management guidelines for obstetrician-gynecologists. No. 82 June 2007. Management of herpes in pregnancy. Obstet Gynecol. 2007;109(6):1489-1498.[PubMed 17569194]

Acyclovir capsule, tablet [prescribing information]. Fort Lee, NJ: DAVA Pharmaceuticals, Inc; April 2014.

Acyclovir injection, powder, lyophilized, for solution [prescribing information]. Schaumberg, IL: AAP Pharmaceuticals, LLC: January 2008.

Acyclovir injection, solution [prescribing information]. Dayton, NJ: AuroMedics Pharma LLC; January 2014.

Acyclovir oral [prescribing information]. Research Triangle Park, NC: GlaxoSmithKline; 2014.

Adour KK, Ruboyianes JM, Von Doersten PG, et al. Bell's palsy treatment with acyclovir and prednisone compared with prednisone alone: a double-blind, randomized, controlled trial. Ann Otol Rhinol Laryngol. 1996;105(5):371-378. doi: 10.1177/000348949610500508.[PubMed 8651631]

Albrecht MA. Treatment of herpes zoster in the immunocompetent host. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed October 18, 2018a.

Albrecht MA. Treatment of varicella (chickenpox) infection. Post TW, ed. UpToDate. Waltham, MA: UpToDate Inc. http://www.uptodate.com. Accessed May 24, 2018b.

Almond MK, Fan S, Dhillon S, Pollock AM, Raftery MJ. Avoiding acyclovir neurotoxicity in patients with chronic renal failure undergoing haemodialysis. Nephron. 1995;69(4):428-432. doi: 10.1159/000188514.[PubMed 7777108]

American Academy of Pediatrics (AAP). In: Kimberlin DW, Brady MT, Jackson MA, Long SA, eds; Red Book: 2015 Report of the Committee on Infectious Diseases. 30th ed. Elk Grove Village, IL: American Academy of Pediatrics; 2015.

American Academy of Pediatrics Committee on Infectious Diseases, “The Use of Oral Acyclovir in Otherwise Healthy Children With Varicella,” Pediatrics, 1993, 91(3):674-6.[PubMed 8382784]

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Brand Names: International

Acic (AE, BH, EE, KW, LV, QA); Aciclodan (DK); Aciclor (VE); Aciclosina (PT); Acicvir (NZ); Aciherpin (PH); Acirax (LK, VN); Acivir (BD, EG, ET, LV); Acivir Eye (IN); Acivirex (GT, HN, NI, SV); Aclovir (FI, TH, TW); Acovir (ZW); ACS (KR); Activir (FR); Acyclo-V (AU, BH); Acyclovenir (IL); Acylene (MY); Acyrax (FI); Acyvir (EC, IT, VN); Aisike (CN); Aisile (CN); Alovir (ZW); Alvoles (TH); Antix (NO); Avir (VE); Avorax (HK); Azost (PH); Bangna (CN); Bearax (SG); Biraxin (PH); Ciclevir (VN); Cicloferon (CR, DO, GT, HN, MX, NI, PA, SV); Cicloviral (CO); Ciclox (PH); Clinovir (ID, TH); Clopes (ID); Clovika (ID); Clovir (KR, PH, PY, QA); Clovirex (LK); Covelay (PH); Cusiviral (MY, QA, SG); Cyclivex (ZA); Cycloherp (HK); Cyclostad (PH); Cyclovax (TR, ZW); Cyclovex (LB); Cyclovir (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZM, ZW); Cyllanvir (PH); Deherp (TH, TW); Dravyr (MY, SG); Duvimex (AE, BH, CY, EG, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Ecuvir (EC); Entir (SG, TH); Erlvirax (SG); Euroclovir (HK); Eurovir (PY); Expit (UY); Gantai (CN); Geavir (DK, SE); Helvevir (CH); Herax (ID); Herpavir (JO); Herperax (ZW); Herpesin (CZ, SK); Herpevex (MY); Herpevir (FR); Herpex (BH, ET, IN, PH, ZW); Herpirax (NL); Herpizyg (TH); Heviran (PL); Isavir (CR, DO, GT, HN, NI, PA, SV); Lermex (TH); Licovir (ID); Lisovyr (AR, CL); Lovir (AE, AU, EG, KW, NZ, PH, QA); Lovire (ZA); Marvir (TH); Matrovir (ID); Medovir (AE, BF, BG, BH, BJ, CI, CY, EG, ET, GH, GM, GN, IQ, IR, JO, KE, KW, LB, LR, LY, MA, ML, MR, MU, MW, MY, NE, NG, OM, QA, SA, SC, SD, SG, SL, SN, SY, TN, TW, TZ, UG, YE, ZM, ZW); Mibeviru (VN); Molavir (ID); Norum (TH); Noviral (QA); Ozvir (AU); Poviral (AR); Qualiclovir (HK); Ranvir (TH); Reclovax (TH); Remex (FR); Skirax (TW); Supraviran (JO, LB); Vacrax (MY); Vermis (TH); Vialesel (ET); Vilerm (SG); Viralex-DS (PH); Viramed (ZW); Viratak (ZW); Viratop (BE); Virax (KR); Virest (HK, SG); Virex (CO); Virherpes (ES); Virless (LK, MY, SG, TW); Viroclear (HK); Virogon (TH); Virolex (HU, RO); Virolox (HR); Viromed (TH); Virpes (AE, JO); Virucid (MT, TR, VN); Virustat (JO); Virzin (DE); Vivir (KR); Wariviron (LB, QA); Xovir (BD); Zevin (TH); Ziverone (MX); Zodiac (KR); Zoral (HK, MY, SG); Zorax (MY, SG); Zorexin (MY); Zoter (ID); Zovir (DK, IS); Zovirax (AE, AR, AT, AU, BB, BD, BE, BF, BG, BH, BJ, BM, BO, BR, BS, CH, CI, CU, CY, CZ, EC, EE, EG, ET, FI, FR, GB, GH, GM, GN, GR, GY, HK, HU, ID, IE, IL, IN, IQ, IR, IT, JM, JO, JP, KE, KR, KW, LB, LR, LU, LV, LY, MA, ML, MR, MT, MU, MW, MY, NE, NG, NL, NO, NZ, OM, PE, PH, PK, PL, PR, PT, PY, QA, RU, SA, SC, SD, SE, SK, SL, SN, SY, TN, TR, TT, TW, TZ, UA, UG, UY, YE, ZA, ZM, ZW); Zoylex (PE); Zyvir (KE)

Last Updated 4/25/20