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Acyclovir (Systemic)

Medically reviewed by Drugs.com. Last updated on Aug 13, 2020.

Pronunciation

(ay SYE kloe veer)

Index Terms

  • Aciclovir
  • ACV
  • Acycloguanosine
  • Acyclovir Sodium
  • Zovirax

Dosage Forms

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

Brand Names: U.S.

  • Zovirax

Pharmacologic Category

  • Antiviral Agent

Pharmacology

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 marginally with multiple small doses vs. 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)

Metabolism

Converted by viral enzymes to acyclovir monophosphate, and further converted to diphosphate then triphosphate (active form) by cellular enzymes

Excretion

Urine (62% to 91% as unchanged drug and metabolite)

Half-Life Elimination

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

Protein Binding

9% to 33%

Special Populations: Renal Function Impairment

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

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.

Off Label Uses

Bell palsy, new onset

Data from meta-analyses and a controlled trial have not demonstrated clear benefit with the use of acyclovir alone or in combination with glucocorticoids for the treatment of Bell palsy [Gagyor 2019], [Numthavaj 2011], [Sullivan 2007].

Based on American Academy of Neurology guidelines on the use of steroids and antivirals for Bell palsy, patients with new-onset Bell palsy might be offered antivirals (in addition to steroids) to increase the probability of facial function recovery; however, benefit has not been established, and if there is a benefit, it is likely modest at best [AAN [Gronseth 2012]].

Cytomegalovirus prevention in low-risk allogeneic hematopoietic cell transplant recipients

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 [ASBMT/IDSA [Tomblyn 2009]].

Herpes simplex virus, esophagitis

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 [Bonis 2020], [Canalejo 2010].

Herpes simplex virus, prevention in immunocompromised patients

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 [ASBMT/IDSA [Tomblyn 2009]].

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 [ASCO/IDSA [Taplitz 2018]].

Clinical experience suggests the utility of acyclovir for prevention of HSV in seropositive solid organ transplant recipients who are not already receiving CMV prophylaxis [AST-IDCOP [Lee 2019]].

Herpes zoster ophthalmicus

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 [Albrecht 2020a].

Varicella zoster virus, acute retinal necrosis

Based on the US Department of Health and Human Services (HHS) guidelines for the prevention and treatment of opportunistic infections in adults and adolescents with HIV, intravenous acyclovir is an effective and recommended agent in the management of varicella zoster virus (VZV) acute retinal necrosis (ARN) in immunocompromised patients (patients with HIV) [HHS [OI adult 2020]].

Clinical experience suggests the utility of intravenous acyclovir in the treatment of VZV ARN in immunocompetent patients [Albrecht 2020b].

Varicella zoster virus, encephalitis

Based on the IDSA clinical practice guideline for the management of encephalitis, IV 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 [Chamizo 2016].

Varicella zoster virus, prevention in immunocompromised patients

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 [ASBMT/IDSA [Tomblyn 2009]].

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 [AST-IDCOP [Pergam 2019]].

Contraindications

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

Dosing: Adult

Note: Use ideal body weight or 40% adjusted body weight for weight-based dosing in obese patients to avoid overdosing and subsequent toxicity (eg, acute renal failure) (Turner 2016; Wong 2017; manufacturer's labeling).

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 2020); some experts only recommend addition of an antiviral to steroid therapy in patients with severe Bell palsy (de Almeida 2014).

Cytomegalovirus, prevention in low-risk allogeneic hematopoietic cell transplant recipients (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); 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, 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 (AST-IDCOP [Lee 2019]; IDSA [Tunkel 2008]; Tunkel 2020).

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 2020; Canalejo Castrillero 2010)

Immunocompromised patients: Oral: 400 mg 5 times daily for 14 to 21 days (Bonis 2020)

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 2020; 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 patients with HIV):

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 (AST-IDCOP [Lee 2019]; CDC [Workowski 2015]; HHS [OI adult 2020]).

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 2020]).

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 2020]).

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 2020).

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 2020). Note: Some experts offer suppressive therapy earlier than 36 weeks' gestation for women who have a first-episode lesion during the third trimester (Riley 2020).

Orolabial: Note: Initiate therapy at earliest symptom.

Immunocompetent and immunocompromised patients (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 immunocompromised patients (AST-IDCOP [Lee 2019]; HHS [OI adult 2020]; Klein 2020)

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 (AST-IDCOP [Lee 2019]; HHS [OI adult 2020]).

Suppressive therapy (eg, for severe and/or frequent recurrences): Oral: 400 mg twice daily (HHS [OI adult 2020]; Rooney 1993). Note: Reassess need periodically (eg, annually) (HHS [OI adult 2020]).

Herpes simplex virus, prevention in immunocompromised patients (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 (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 (AST-IDCOP [Lee 2019]); some experts recommend continuing for 3 to 6 months after transplantation and during periods of lymphodepletion associated with treatment of rejection (Fishman 2020).

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 patients with HIV):

Acute localized dermatomal: Oral: 800 mg 5 times daily for 7 to 10 days; consider longer duration if lesions resolve slowly (AST-IDCOP [Pergam 2019]; HHS [OI adult 2020]).

Extensive cutaneous lesions or visceral involvement: IV: 10 mg/kg/dose every 8 hours (AST-IDCOP [Pergam 2019]; HHS [OI adult 2020]). 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 2020]).

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 2020a)

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 2020b; Arvin 1996; Wallace 1992)

Immunocompromised patients (including patients with HIV):

Severe or complicated infection: IV: 10 mg/kg/dose every 8 hours for 7 to 10 days (AST-IDCOP [Pergam 2019]; HHS [OI adult 2020]). May switch to oral antiviral after defervescence if no evidence of visceral involvement; continue until all lesions have crusted (AST-IDCOP [Pergam 2019]; HHS [OI adult 2020]).

Uncomplicated infection: Oral: 800 mg 5 times daily for 5 to 7 days (HHS [OI adult 2020]); some experts recommend a minimum duration of 7 days, extending the course until all lesions have crusted (AST-IDCOP [Pergam 2019]).

Varicella zoster virus, acute retinal necrosis (off-label use): IV: 10 mg/kg/dose every 8 hours for 10 to 14 days, followed by ~6 weeks of valacyclovir (Albrecht 2020a; HHS [OI adult 2020]); in patients with HIV, intravitreal ganciclovir should be added (HHS [OI adult 2020]).

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 hematopoietic cell transplant 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 (AST-IDCOP [Pergam 2019]; Fishman 2020).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Geriatric

Refer to adult dosing; use with caution.

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).

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 (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.

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) (HHS [OI adult 2020]; HHS [OI pediatric 2019]).

Infants and Children: IV: 10 to 15 mg/kg/dose every 8 hours for 10 to 14 days (HHS [OI pediatric 2019]).

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 (HHS [OI adult 2020]).

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 (HHS [OI pediatric 2019]).

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 (Red Book [AAP 2018]).

Hospitalized patient:

Infants and Children <2 years: IV: 10 mg/kg/dose every 8 hours for 7 to 10 days (Red Book [AAP 2018]).

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 (Red Book [AAP 2018]).

Immunocompromised host (non-HIV-exposed/-infected): IV: Infants, Children, and Adolescents: 10 mg/kg/dose every 8 hours for 7 to 10 days (Red Book [AAP 2018]).

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 (HHS [OI pediatric 2019]).

Adolescents (alternative therapy): Oral: 800 mg 5 times daily for 7 to 10 days, longer if lesions resolve slowly (HHS [OI adult 2020]).

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 (HHS [OI pediatric 2019]).

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 (HHS [OI pediatric 2019]).

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 (HHS [OI adult 2020]).

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 (AAP [Kimberlin 2013]; Bradley 2019; CDC [Workowski 2015]; HHS [OI pediatric 2019]; Red Book [AAP 2018]).

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 (AAP [Kimberlin 2013]; Bradley 2019; Kimberlin 2011; Red Book [AAP 2018]).

HSV 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 (Bradley 2019; HHS [OI pediatric 2019]; Red Book [AAP 2018]).

Children ≥12 years and Adolescents: IV: 10 mg/kg/dose every 8 hours for 14 to 21 days (HHS [OI pediatric 2019]; Red Book [AAP 2018]).

HSV 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 (Bradley 2019; Red Book [AAP 2018]).

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 2018]).

HIV-exposed/-infected:

Children: Oral: 20 mg/kg/dose 3 times daily for 7 to 10 days; maximum dose: 400 mg/dose (HHS [OI pediatric 2019]).

Adolescents: Oral: 400 mg 3 times daily for 5 to 10 days (HHS [OI adult 2020]).

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 2018]).

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 2019; HHS [OI pediatric 2019]).

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 (CDC [Workowski 2015]; Red Book [AAP 2018]).

HIV-exposed/-positive: Adolescents: Oral: 400 mg 3 times daily for 5 to 10 days (HHS [OI adult 2020]).

Suppression, chronic:

Non-HIV-exposed/-infected:

Children <12 years: Limited data available: Oral: 20 mg/kg/dose twice daily; maximum dose: 400 mg/dose (Bradley 2019).

Children and Adolescents ≥12 years: Oral: 400 mg twice daily; reassess therapy after 12 months (Bradley 2019; CDC [Workowski 2015]; Red Book [AAP 2018]).

HIV-exposed/-infected:

Infants and Children: Oral: 20 mg/kg/dose twice daily; maximum dose: 800 mg/dose (HHS [OI pediatric 2019]).

Adolescents: Oral: 400 mg twice daily (HHS [OI adult 2020]).

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 (Bradley 2019; Cernik 2008; Red Book [AAP 2018]).

HIV-exposed/-infected (HHS [OI pediatric 2019]):

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 (HHS [OI adult 2020]).

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.

HSV mucocutaneous infection:

Immunocompetent host: Infants, Children, and Adolescents:

Treatment:

IV: 5 mg/kg/dose every 8 hours (Bradley 2019).

Oral: 20 mg/kg/dose 4 times daily for 5 to 7 days; maximum dose: 800 mg/dose (Bradley 2019; Red Book [AAP 2018]).

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 2019).

Immunocompromised host:

Treatment:

IV:

Infants and Children: IV: 10 mg/kg/dose every 8 hours for 7 to 14 days (Red Book [AAP 2018]).

Adolescents: IV: 5 to 10 mg/kg/dose every 8 hours; change to oral therapy after lesions begin to regress (HHS [OI adult 2020]; Red Book [AAP 2018]).

Oral: Children ≥2 years and Adolescents: 1,000 mg/day in 3 to 5 divided doses for 7 to 14 days (Red Book [AAP 2018]).

Suppression, chronic (cutaneous, ocular) episodes:

Non-HIV-exposed/-infected:

Children ≥12 years and Adolescents: Oral: 400 mg twice daily; reassess at 12 months (Red Book [AAP 2018]).

HIV-exposed/-infected:

Infants and Children: Oral: 20 mg/kg/dose twice daily; maximum dose: 800 mg/dose; reassess after 12 months (HHS [OI pediatric 2019]).

Adolescents: Oral: 400 mg twice daily; reassess at 12 months (HHS [OI adult 2020]).

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 (Red Book [AAP 2018]).

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 (HHS [OI pediatric 2019]; Red Book [AAP 2018]).

HSV, acute retinal necrosis, treatment (HIV-exposed/-infected): Infants and Children (HHS [OI pediatric 2019]):

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 (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 2018]).

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 2018]).

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

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/-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 (HHS [OI pediatric 2019]).

Infants and Children: Oral: 20 mg/kg/dose 4 times daily for 7 days; maximum dose: 800 mg/dose (HHS [OI pediatric 2019]).

Adolescents: Oral: 800 mg 5 times daily for 5 to 7 days (HHS [OI adult 2020]).

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 2018]).

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 (Bradley 2019; Red Book [AAP 2018]).

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 2019; Red Book [AAP 2018]); some experts recommend 15 to 20 mg/kg/dose for severe disseminated or CNS infection (Bradley 2019).

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 (Bradley 2019; Red Book [AAP 2018]).

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 (Bradley 2019; Red Book [AAP 2018]).

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 (HHS [OI pediatric 2019]).

Adolescents (alternative therapy): Oral: 800 mg 5 times daily for 5 to 7 days (HHS [OI adult 2020]).

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 (HHS [OI pediatric 2019]).

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 (HHS [OI pediatric 2019]).

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 (HHS [OI adult 2020]).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Obesity

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 in morbidly obese patients (BMI ≥ 40 kg/m2) using a single acyclovir IV dose, IBW weight-based dosing 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, herpes simplex virus encephalitis), some clinicians use adjusted body weight (AdjBW) to determine the IV dose (AdjBW=IBW + [0.4 x (actual body weight-IBW)]) (Turner 2016; Wong 2017), although this approach has not been evaluated in clinical studies.

Reconstitution

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.

Administration

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

Dietary Considerations

Some products may contain sodium.

Storage

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.

Drug Interactions

Cladribine: Agents that Undergo Intracellular Phosphorylation may diminish the therapeutic effect of Cladribine. 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. Monitor therapy

Foscarnet: May enhance the nephrotoxic effect of Acyclovir-Valacyclovir. Avoid combination

Mycophenolate: Acyclovir-Valacyclovir may increase the serum concentration of Mycophenolate. Mycophenolate may increase the serum concentration of Acyclovir-Valacyclovir. Monitor therapy

Talimogene Laherparepvec: Antiherpetic Antivirals may diminish the therapeutic effect of Talimogene Laherparepvec. Monitor therapy

Tenofovir Products: Acyclovir-Valacyclovir may increase the serum concentration of Tenofovir Products. Tenofovir Products may increase the serum concentration of Acyclovir-Valacyclovir. Monitor therapy

Theophylline Derivatives: CYP1A2 Inhibitors (Weak) may increase the serum concentration of Theophylline Derivatives. Exceptions: Dyphylline. 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. 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. Avoid combination

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

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

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

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).

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.

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.

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]).

Patient Education

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.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Nausea

• Vomiting

• Loss of strength and energy

• Injection site irritation

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

• 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; trouble speaking or thinking; change in balance; or fever.

• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, 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 limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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