Acyclovir Sodium

Name: Acyclovir Sodium

Introduction

Antiviral; purine nucleoside analog derived from guanine.403 409

Acyclovir Sodium Dosage and Administration

Administration

Administer orally or by IV infusion.403 409

Parenteral preparation should not be administered orally or by IM or sub-Q injection and should not be applied topically or to the eye.409

Oral Administration

Administer without regard to meals.213 403

IV Infusion

For solution and drug compatibility information, see Compatibility under Stability.

Reconstitution

Reconstitute vial containing 500 mg or 1 g of acyclovir powder with 10 or 20 mL of sterile water for injection, respectively, to provide a solution containing 50 mg/mL.409

Shake well to ensure complete dissolution.409 Must be diluted further before IV administration.409

Dilution

For IV infusion, dilute concentrate containing acyclovir 25 or 50 mg/mL with a compatible IV solution (see Solution Compatibility under Stability) to a concentration of ≤7 mg/mL.409

Alternatively, dilute solutions reconstituted from powder prior to IV infusion with 50–125 mL of a compatible IV infusion solution.409 (See Solution Compatibility under Stability.) For fluid-restricted patients, dilute reconstituted solution in a ratio of approximately 1 part reconstituted solution to 9 parts infusion solution to a concentration of ≤7 mg/mL.409

Rate of Administration

Administer by IV infusion at a constant rate over at least 1 hour.409 Do not administer by rapid IV infusion (over <10 minutes) or rapid IV injection.409 (See Renal Effects under Cautions.)

Ensure adequate hydration.409

Dosage

Available as acyclovir and acyclovir sodium; dosage expressed in terms of acyclovir.409

Pediatric Patients

Mucocutaneous, Ocular, and Systemic Herpes Simplex Virus (HSV) Infections Treatment of Mucocutaneous HSV Infections Oral†

Immunocompromised children: 1 g daily given in 3–5 divided doses for 7–14 days.322

IV

Immunocompromised children <12 years of age: 10 mg/kg every 8 hours for 7–14 days.322 381 409

HIV-infected or immunocompromised adolescents and children ≥12 years of age: 5 mg/kg every 8 hours for 7–14 days.322 381 409 412 Alternatively, after lesions begin to regress, consider switching to oral acyclovir in a dosage of 400 mg 3 times daily and continue until lesions are completely healed.412

HSV Gingivostomatitis Oral†

HIV-infected children with mild, symptomatic gingivostomatitis: CDC and others recommend 20 mg/kg (up to 400 mg) 3 times daily for 7–14 days.413

Immunocompetent children: 15 mg/kg (up to 200 mg) 5 times daily for 7 days has been used in a few children 1–6 years of age.418

IV

HIV-infected children with moderate to severe gingivostomatitis: CDC and others recommend 5–10 mg/kg 3 times daily for 7–14 days.413 Consider chronic oral suppressive or maintenance therapy (secondary prophylaxis) in those with frequent or severe recurrences of gingivostomatitis.413

Chronic Suppressive or Maintenance Therapy (Secondary Prophylaxis) of HSV Infections† Oral

HIV-infected infants and children: 80 mg/kg daily (up to 1 g daily) in 3 or 4 divided doses.404

HIV-infected adolescents: 200 mg 3 times daily or 400 mg twice daily.404

Prophylaxis Against Recurrent Ocular HSV Disease† Oral

Children ≥12 years of age: 400 mg twice daily.408 419 AAP recommends 80 mg/kg daily (up to 1 g daily) given in 3 divided doses.322

Optimum duration of prophylaxis unclear;419 has been continued for 12–18 months in clinical studies.408 419

Treatment of HSV Encephalitis or Disseminated Disease IV

Immunocompromised children: 20 mg/kg every 8 hours in those 3 months to 12 years of age381 409 and 10–15 mg/kg every 8 hours in those ≥12 years of age.211 246 322 409 413 Manufacturer recommends a treatment duration of 10 days,409 but AAP and others recommend 14–21 days for disseminated or CNS infections.235 236 311 322 381 413

HIV-infected children: CDC and others recommend 10 mg/kg or 500 mg/m2 3 times daily for 21 days.413

HIV-infected adolescents: CDC and others recommend 10 mg/kg 3 times daily for 14–21 days.412

Treatment of Neonatal HSV Infections IV

Neonates and children ≤3 months of age: Manufacturer recommends 10 mg/kg every 8 hours for 10 days.409

Neonates and children ≤3 months of age: AAP recommends 20 mg/kg every 8 hours given for 14 days for infections of skin, eyes, or mouth or 21 days for disseminated or CNS infections.322

HIV-infected or -exposed neonates: CDC and others recommend 20 mg/kg 3 times daily given for 14 days for infections of skin, eyes, or mouth or 21 days for disseminated or CNS infections.413

Prevention of HSV Recurrence in Hematopoietic Stem Cell Transplant (HSCT) Recipients† Oral

HSV-seropositive children: 0.6–1 g daily given in 3–5 divided doses.414

HSV-seropositive adolescents: 200 mg 3 times daily.414

Initiate prophylaxis at beginning of conditioning therapy and continue until engraftment or until mucositis resolves (approximately 30 days after allogeneic HSCT).414 Routine prophylaxis for >30 days after HSCT not recommended.414

IV

HSV-seropositive children: 250 mg/m2 every 8 hours or 125 mg/m2 every 6 hours.414

HSV-seropositive adolescents: 250 mg/m2 every 12 hours.

Initiate prophylaxis at beginning of conditioning therapy and continue until engraftment or until mucositis resolves (approximately 30 days after allogeneic HSCT).414 Routine prophylaxis for >30 days after HSCT not recommended.414

Genital Herpes Treatment of First Episodes Oral

Children: AAP recommends 40–80 mg/kg daily (maximum 1 g daily) given in 3 or 4 divided doses for 5–10 days.322

Adolescents: CDC recommends 400 mg 3 times daily or 200 mg 5 times daily for 7–10 days;244 duration may be extended if healing is incomplete after 10 days.244

HIV-infected adolescents: CDC and others recommend 20 mg/kg (up to 400 mg) or 400 mg 3 times daily for 7–14 days.412

IV

Adolescents and children ≥12 years of age with severe initial episodes: 5–10 mg/kg every 8 hours.244 381 409 410

Manufacturer and some clinicians recommend 5–7 days of IV acyclovir;381 409 CDC states IV acyclovir should be given for 2–7 days or until clinical improvement occurs, followed by an oral antiviral to complete at least 10 days of treatment.244

Episodic Treatment of Recurrent Episodes Oral

Adolescents: CDC recommends 400 mg 3 times daily for 5 days, 800 mg twice daily for 5 days, or 800 mg 3 times daily for 2 days.244

HIV-infected adolescents: CDC recommends 400 mg 3 times daily for 5–10 days.244 Alternatively, acyclovir can be given for 7–14 days.412

Initiate episodic therapy at the earliest prodromal sign or symptom of recurrence or within 1 day of the onset of lesions.244 403

Chronic Suppression of Recurrent Episodes Oral

Adolescents: CDC recommends 400 mg twice daily.244

HIV-infected adolescents: CDC recommends 400–800 mg 2 or 3 times daily.244

Discontinue periodically (e.g., after 12 months or once yearly) to reassess need for continued therapy.244 403

Varicella-Zoster Infections Treatment of Varicella (Chickenpox) Oral

Immunocompetent children ≥2 years of age: Manufacturer recommends 20 mg/kg 4 times daily (maximum 80 mg/kg daily) for 5 days in those weighing ≤40 kg and 800 mg 4 times daily for 5 days in those weighing >40 kg.403 Alternatively, some clinicians recommend 20 mg/kg (up to 800 mg) 4 times daily for 5 days.239 322 329 331 336 368 381 410

HIV-infected children with mild immunosuppression and mild varicella: CDC and others recommend 20 mg/kg (up to 800 mg) 4 times daily for 7 days or until no new lesions have appeared for 48 hours.413

Initiate therapy at the earliest sign or symptom of infection (within 24 hours of onset of rash).368 403

IV

Immunocompromised children: AAP recommends 10 mg/kg 3 times daily for 7–10 days for those <1 year of age and 500 mg/m2 3 times daily for 7–10 days in those ≥1 year of age.322

Immunocompromised adolescents and children: Some clinicians recommend 20 mg/kg every 8 hours for 7–10 days in those ≤12 years of age and 10 mg/kg every 8 hours for 7 days in those >12 years of age.381

HIV-infected children with moderate or severe immunosuppression and varicella associated with high fever or necrotic lesions: CDC and others recommend 10 mg/kg 3 times daily for 7 days or until no new lesions have appeared for 48 hours.413 Alternatively, a dosage of 500 mg/m2 every 8 hours has been suggested for those ≥1 year of age.413

HIV-infected adolescents: CDC and others recommend 10 mg/kg every 8 hours for 7–10 days.412 After defervescence and if there is no evidence of visceral involvement, switch to oral acyclovir in a dosage of 800 mg 4 times daily.412

Treatment of Herpes Zoster (Shingles, Zoster) Oral

Immunocompetent children ≥12 years of age: 800 mg every 4 hours 5 times daily (4 g daily) for 5–10 days.261 284 285 309 322 381 403 410

HIV-infected children with mild immunosuppression and mild varicella: CDC and others recommend 20 mg/kg (up to 800 mg) 4 times daily for 7–10 days.413

Initiate therapy preferably within 48 hours of onset of rash.261 284 285 309 322 381 403 410

IV

Immunocompetent children: AAP recommends 10 mg/kg 3 times daily for 7–10 days for those <1 year of age and 500 mg/m2 3 times daily for 7–10 days in those ≥1 year of age.322

Immunocompromised children: 20 mg/kg every 8 hours for 7–10 days in those <12 years of age381 322 409 413 and 10 mg/kg every 8 hours for 7 days in those ≥12 years of age.381 409 410

HIV-infected children with severe immunosuppression and extensive multidermatomal zoster or zoster with trigeminal nerve involvement: CDC and others recommend 10 mg/kg 3 times daily for 7–10 days.413

HIV-infected adolescents: CDC and others recommend 10 mg/kg every 8 hours until cutaneous and visceral disease resolves.412

Adults

Mucocutaneous, Ocular, and Systemic Herpes Simplex Virus (HSV) Infections Treatment of Mucocutaneous HSV Infections Oral†

Immunocompromised or HIV-infected adults: 400 mg every 4 hours while awake (5 times daily) for 7–14 days.381 410

IV

Immunocompromised or HIV-infected adults: CDC and others recommend 5 mg/kg every 8 hours for 7–14 days.381 409 412 Alternatively, after lesions begin to regress, consider switching to oral acyclovir in a dosage of 400 mg 3 times daily and continue until lesions are completely healed.412

Chronic Suppressive or Maintenance Therapy (Secondary Prophylaxis) of HSV Infections† Oral

HIV-infected adults: 200 mg 3 times daily or 400 mg twice daily.404

Treatment of Orolabial HSV Infections Oral

400 mg 5 times daily for 5 days.381

HIV-infected adults: CDC and others recommend 400 mg 3 times daily for 7–14 days.381 412

Treatment of HSV Keratitis† Oral

HIV-infected adults: 400 mg 5 times daily.407 Long-term therapy may be required to prevent recurrence.407

Prophylaxis Against Recurrent Ocular HSV Disease† Oral

Immunocompetent adults: 400 mg twice daily.408 419 420 Optimum duration of prophylaxis unclear;419 has been continued for 12–18 months in clinical studies.408 419

Treatment of HSV Encephalitis or Disseminated Disease IV

10–15 mg/kg every 8 hours.211 246 322 381 409 412 Manufacturer recommends a treatment duration of 10 days,409 but CDC and others recommend 14–21 days for disseminated or CNS infections.235 236 311 381 412

HIV-infected adults: CDC and others recommend 10 mg/kg 3 times daily for 14–21 days.412

Prevention of HSV Recurrence in Hematopoietic Stem Cell Transplant (HSCT) Recipients† Oral

HSV-seropositive adults: 200 mg 3 times daily initiated at beginning of conditioning therapy and continued until engraftment or until mucositis resolves (i.e., approximately 30 days after allogeneic HSCT).414 Routine prophylaxis for >30 days after HSCT not recommended.414

IV

HSV-seropositive adults: 250 mg/m2 every 12 hours initiated at beginning of conditioning therapy and continued until engraftment or until mucositis resolves (i.e., approximately 30 days after allogeneic HSCT).414 Routine prophylaxis for >30 days after HSCT not recommended.414

Genital Herpes Treatment of First Episodes Oral

Manufacturer recommends 200 mg every 4 hours while awake (5 times daily) for 10 days.403

CDC and others recommend 400 mg 3 times daily or 200 mg 5 times daily for 7–10 days;244 313 381 410 duration may be extended if healing is incomplete after 10 days.244

HIV-infected adults: CDC and others recommend 400 mg 3 times daily for 7–14 days.412

IV

Adults with severe initial episodes: 5–10 mg/kg every 8 hours.244 313 381 409 410

Manufacturer and some clinicians recommend 5–7 days of IV acyclovir;313 381 409 CDC states IV acyclovir should be given for 2–7 days or until clinical improvement occurs, followed by an oral antiviral to complete at least 10 days of therapy.244

Treatment of First Episode of Herpes Proctitis† Oral

400 mg 5 times daily for 10 days or until clinical resolution occurs.305

Episodic Treatment of Recurrent Episodes of Genital Herpes Oral

Manufacturer recommends 200 mg every 4 hours while awake (5 times daily) for 5 days.403

CDC recommends 400 mg 3 times daily for 5 days, 800 mg twice daily for 5 days, or 800 mg 3 times daily for 2 days.244

HIV-infected adults: CDC recommends 400 mg 3 times daily for 5–10 days.244 Alternatively, acyclovir can be given for 7–14 days.412

Initiate episodic therapy at the earliest prodromal sign or symptom of recurrence or within 1 day of the onset of lesions.244 403 410

Chronic Suppression of Recurrent Episodes of Genital Herpes Oral

400 mg twice daily;244 313 381 403 alternatively, 200 mg 3–5 times daily.403

HIV-infected adults: 400–800 mg 2 or 3 times daily.244

Discontinue periodically (e.g., after 12 months or once yearly) to reassess need for continued therapy.244 403

Varicella-Zoster Infections Treatment of Varicella (Chickenpox) Oral

20 mg/kg (up to 800 mg) 4 times daily for 5 days.239 322 329 331 336 353 368 381 403 410 412

Initiate therapy at the earliest sign or symptom of infection (within 24 hours of onset of rash).368 403

IV, then Oral

HIV-infected or immunocompromised adults: CDC and others recommend 10 mg/kg every 8 hours for 7–10 days.381 412 After defervescence and if there is no evidence of visceral involvement, switch to oral acyclovir in a dosage of 800 mg 4 times daily.412

Treatment of Herpes Zoster (Shingles, Zoster) Oral

800 mg every 4 hours (5 times daily) for 7–10 days.261 284 285 309 322 381 403 410

Initiate therapy preferably within 48 hours of onset of rash.261 284 285 309 322 381 410

IV

HIV-infected or immunocompromised adults: CDC and others recommend 10 mg/kg every 8 hours for 7 days or until cutaneous and visceral disease resolves.381 409 410 412

Treatment of Herpes Zoster Ophthalmicus† Oral

Immunocompetent adults: 600 mg every 4 hours 5 times daily (3 g daily) for 10 days.281 282 286

Initiate therapy within 72 hours (but no later than 7 days) after rash onset.281 282 286

IV, then Oral

HIV-infected adults: 10 mg/kg IV 3 times daily for 7 days followed by 800 mg orally 3–5 times daily has been used.407

Treatment of Dermatomal Herpes Zoster† Oral

Immunocompromised adults: 800 mg 5 times daily for 10 days has been used,219 225 but CDC and others recommend oral famciclovir or valacyclovir for localized dermal infections in HIV-infected individuals.412

Prescribing Limits

Pediatric Patients

Oral

Maximum 20 mg/kg 4 times daily (1 g daily)322 403 in children ≥2 years of age weighing ≤40 kg.403

IV

Maximum 20 mg/kg every 8 hours.409

Adults

Oral

800 mg per dose.239 322 329 331 336 353 368 381 410

IV

Maximum 20 mg/kg every 8 hours.409

Special Populations

Renal Impairment

Adjustment of Usual Oral Dosage Oral Dosage in Renal Impairment403

Usual Dosage Regimen

Clcr (mL/min per 1.73 m2)

Adjusted Dosage Regimen

200 mg every 4 h 5 times daily

>10

No adjustment necessary

0–10

200 mg every 12 h

400 mg every 12 h

>10

No adjustment necessary

0–10

200 mg every 12 h

800 mg every 4 h 5 times daily

>25

No adjustment necessary

10–25

800 mg every 8 h

0–10

800 mg every 12 h

Hemodialysis

Give supplemental oral dose immediately after each dialysis period.403

Peritoneal Dialysis

Supplemental doses do not appear necessary.403

Adjustment of Usual IV Dosage IV Dosage in Renal Impairment409

Clcr (mL/min per 1.73 m2)

Percent of Recommended Dose

Dosing Interval (hours)

>50

100%

8

25–50

100%

12

10–25

100%

24

0–10

50%

24

Hemodialysis

Adjust dosing schedule so that a supplemental IV dose is administered immediately after each dialysis period.409

CAPD

Supplemental doses do not appear necessary.316

Alternative IV Dosage Regimens for End-Stage Renal Disease

93–185 mg/m2 as a loading dose, followed by a maintenance dosage of 35–70 mg/m2 every 8 hours, and 56–185 mg/m2 immediately after dialysis.a

250–500 mg/m2 as a loading dose, followed by a maintenance dosage of 250–500 mg/m2 every 48 hours, and 150–500 mg/m2 immediately after dialysis.a

2.5 mg/kg every 24 hours and 2.5 mg/kg after each dialysis period.a

HIV-infected Patients with Impaired Renal Function (Oral Administration) Oral Dosage for HIV-infected Patients with Impaired Renal Function (Based on Usual Dosage of 200–800 mg Every 4–6 Hours)411

Clcr (mL/min per 1.73 m2)

Adjusted Dosage Regimen

>80

No adjustment necessary

50–80

200–800 mg every 6–8 h

25–50

200–800 mg every 8–12 h

10–25

200–800 mg every 12–24 h

<10

200–400 mg every 24 h

Hemodialysis

Give supplemental usual oral dose after each dialysis period.411

HIV-infected Patients with Impaired Renal Function (IV Administration) IV Dosage for HIV-infected Patients with Impaired Renal Function (Based on Usual Dosage of 5 mg/kg Every 8 hours)409411

Clcr (mL/min per 1.73 m2)

Adjusted Dosage Regimen

>80

No adjustment necessary

50–80

No adjustment necessary

25–50

5 mg/kg every 12–24 hours

10–25

5 mg/kg every 12–24 hours

<10

2.5 mg/kg every 24 hours

Hemodialysis

Adjust dosing schedule so that daily IV dose is given after hemodialysis on dialysis days.411

Geriatric Patients

Cautious dosage selection; reduced dosage may be needed because of age-related decreases in renal function.403 409 (See Geriatric Use under Cautions.)

Obese Patients

Use ideal body weight to determine IV dosage.409

Acyclovir Sodium Pharmacokinetics

Absorption

Bioavailability

Absorption from GI tract is variable and incomplete; 10–30% of an oral dose may be absorbed.213 233 403 Peak plasma concentrations usually are attained within 1.5–2.5 hours after oral administration.213 232

Commercially available capsules and oral suspension are bioequivalent.403

Food

Food does not appear to affect GI absorption.213 403

Distribution

Extent

Widely distributed into body tissues and fluids including the brain, kidney, saliva, lung, liver, muscle, spleen, uterus, vaginal mucosa, CSF, herpetic vesicular fluid, and semen.266 a

Following IV administration in patients with uninflamed meninges, CSF concentrations of the drug are about 50% of concurrent serum concentrations.a

Crosses placenta following oral or IV administration;245 421 cord blood concentrations may be higher than maternal plasma concentrations.421

Distributed into milk following oral or IV administration; milk concentrations may be higher than concurrent maternal plasma concentrations.251 308 421

Plasma Protein Binding

9–33%.403 409

Elimination

Metabolism

Metabolized partially to 9-carboxymethoxymethylguanine;a also converted intracellularly in cells infected with herpesviruses to acyclovir triphosphate, the pharmacologically active form of the drug.354 403

Elimination Route

Excreted principally in urine as unchanged drug.a

Half-life

Adults with normal renal function: initial serum half-life averages 0.34 hour and terminal half-life averages 2.1–3.5 hours.a

Children >1 year of age: elimination half-life similar to that in adults.a

Neonates: half-life depends principally on maturity of renal mechanisms for clearance.a

Special Populations

Renal impairment may reduce clearance.a

Actions and Spectrum

  • Active against various Herpesviridae including herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus (VZV), Epstein-Barr virus, herpes virus simiae (B virus), and cytomegalovirus (CMV).354 403 409 Less active against CMV than many other Herpesviridae.354

  • In cells infected with herpes virus, is converted to acyclovir triphosphate,354 403 which inhibits viral DNA synthesis and viral replication by incorporating into viral DNA and by competing with deoxyguanosine triphosphate for viral DNA polymerase.a 403 409

  • Acyclovir resistance may result from qualitative or quantitative changes in thymidine kinase and/or DNA polymerase (e.g., absence or low concentrations of enzyme, alterations in substrate specificity).a 403 409

  • Resistance to acyclovir reported in HSV and VZV.244 381 413

  • Acyclovir-resistant HSV or VZV usually resistant to famciclovir and valacyclovir, but may be susceptible to foscarnet.244 381 413

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

Acyclovir

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral

Capsules

200 mg*

Acyclovir Capsules

Actavis, Ranbaxy, Teva, Watson

Zovirax (with parabens)

GlaxoSmithKline

Suspension

200 mg/5 mL*

Acyclovir Suspension (with parabens)

Actavis, Hi-Tech

Zovirax (with glycerin, parabens, and sorbitol)

GlaxoSmithKline

Tablets

400 mg*

Acyclovir Tablets

Actavis, Ranbaxy, Teva, Watson

Zovirax (with povidone)

GlaxoSmithKline

800 mg*

Acyclovir Tablets

Actavis, Ranbaxy, Teva, Watson

Zovirax (with povidone)

GlaxoSmithKline

Acyclovir Sodium

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

For injection, concentrate, for IV infusion only

50 mg (of acyclovir) per mL (500 mg, 1 g)

Acyclovir Sodium Injection

Abraxis

For injection, for IV infusion only

500 mg (of acyclovir)

Acyclovir Sodium for Injection

Abraxis, Bedford, Sicor

Zovirax

GlaxoSmithKline

1 g (of acyclovir)

Acyclovir Sodium for Injection

Abraxis, Bedford, Sicor

Zovirax

GlaxoSmithKline

Acyclovir Sodium in Sodium Chloride

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, for IV infusion only

5 mg (of acyclovir) per mL [500 mg, 1 g] in 0.9% Sodium Chloride

Acyclovir Sodium Injection in 0.9% Sodium Chloride Injection Redi-Infusion

ESI Lederle

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