Generic Name: Acyclovir
Class: Nucleosides and Nucleotides
VA Class: AM800
CAS Number: 59277-89-3
Introduction
Antiviral; purine nucleoside analog derived from guanine.403 409
Uses for Zovirax
Mucocutaneous, Ocular, and Systemic Herpes Simplex Virus (HSV) Infections
Treatment of initial and recurrent mucocutaneous HSV-1 and HSV-2 infections (e.g., orofacial, esophageal, genital, nasal, labial) in immunocompromised adults, adolescents, and children, including HIV-infected individuals.322 381 396 409 410 412 413 Drug of choice.322 381 396 410 412 413
Chronic suppressive or maintenance therapy (secondary prophylaxis) of recurrent HSV infections† in immunocompromised adults, adolescents, and children, including HIV-infected individuals who have frequent or severe recurrences.322 392 404 412
Treatment of orolabial HSV infections (including gingivostomatitis) in immunocompetent† adults and children;322 381 418 generally ineffective or minimally effective for prevention of recurrence of herpes labialis† in immunocompetent individuals.322 422
Treatment of eczema herpeticum† in patients with a history of atopic dermatitis.223 224
Treatment of HSV keratitis† in HIV-infected patients.407
Prophylaxis against recurrence of ocular HSV disease† in immunocompetent adults and children ≥12 years of age who had ocular HSV disease (blepharitis, conjunctivitis, epithelial keratitis, stromal keratitis, iritis) in one or both eyes within the preceding 12 months.408 419 Has been used for prophylaxis after penetrating keratoplasty for herpetic keratitis.420
Drug of choice for treatment of HSV encephalitis.211 212 246 248 322 381 395 409 410 412 413
Drug of choice for treatment of neonatal HSV infections, including mucocutaneous infections, infections involving skin, eyes, and mouth, and disseminated or CNS infections.244 322 324 353 356 381 395 408 409 410 413
Drug of choice for prevention of HSV recurrence† in hematopoietic stem cell transplant (HSCT) recipients seropositive for HSV; such prophylaxis not indicated in those seronegative for HSV.414
Genital Herpes
Treatment of initial episodes of genital herpes in adults and adolescents,206 207 208 244 305 313 322 381 403 409 including HIV-infected individuals.412
Treatment of first episodes of herpes proctitis†.305
Episodic treatment of recurrent episodes of genital herpes in adults and adolescents,244 313 322 381 403 including HIV-infected individuals.244 412
Chronic suppressive therapy of recurrent episodes of genital herpes in adults and adolescents,202 203 210 242 244 313 317 318 319 320 321 322 381 384 386 403 including HIV-infected individuals.244 412
CDC and others recommend oral acyclovir, oral famciclovir, or oral valacyclovir as drugs of choice for treatment of initial episodes of genital herpes and for episodic treatment or chronic suppressive therapy of recurrent genital herpes.244 313 381 412
Varicella-Zoster Infections
Treatment of varicella (chickenpox) in immunocompromised adults, adolescents, and children, including HIV-infected individuals.249 277 279 322 352 353 368 403 409 410 412 413 Drug of choice.249 277 279 322 352 353 368 410 412 413
Treatment of varicella (chickenpox) in immunocompetent adults, adolescents, and children.239 322 337 338 340 344 348 352 353 368 381 394 403 410 415 Varicella usually is a self-limited disease in otherwise healthy individuals and the role of acyclovir for treatment in these individuals is controversial;239 329 330 331 332 333 335 336 337 338 344 349 350 355 368 routine use not recommended by AAP and other clinicians.322 331 332 335 344 345 368
Treatment of herpes zoster (shingles, zoster) in immunocompetent261 284 285 309 353 or immunocompromised adults, adolescents, and children, including HIV-infected individuals.322 358 359 381 403 409 410 412 413 Drug of choice for serious or disseminated herpes zoster in immunocompromised patients.381 413
Treatment of herpes zoster ophthalmicus† in HIV-infected patients.407 412
Treatment of dermatomal herpes zoster in immunocompromised patients† including transplant recipients225 and HIV-infected patients.219 407 412
Alternative to varicella-zoster immune globulin (VZIG) for postexposure prophylaxis of VZV infection† in HSCT recipients.414 Although long-term prophylaxis not routinely recommended for prevention of recurrent VZV infections in HSCT recipients, such prophylaxis may be considered in those with severe, long-term immunodeficiency.414
Prevention of Cytomegalovirus (CMV) Disease in Transplant Recipients
Has been used for prevention of CMV disease† in solid organ transplant recipients354 360 363 364 365 366 367 398 399 414 and bone marrow transplant (BMT) recipients at risk for the disease; data regarding efficacy are conflicting.354 360 365 367 382
Has been used for prevention of CMV disease† in HSCT recipients; generally ineffective after autologous HSCT.414 Ganciclovir is drug of choice for prevention of CMV following autologous or allogeneic HSCT in adults, adolescents, and children.414
Not effective for prevention of CMV disease in HIV-infected individuals.404
Epstein-Barr Virus Infections and Disorders
Treatment of uncomplicated or complicated infectious mononucleosis, chronic infectious mononucleosis, and various disorders (e.g., oral hairy leukoplakia) associated with Epstein-Barr virus infections†;262 270 271 272 369 396 efficacy appears to be variable.230 262 272 273 274 275 276 369
Zovirax 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
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
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)
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)
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
Cautions for Zovirax
Contraindications
Known hypersensitivity to acyclovir or valacyclovir.403 409
Warnings/Precautions
Warnings
Renal Effects
Increased BUN and/or Scr, anuria, and hematuria have been reported.403 409 Transient increases in BUN and/or Scr and decreases in Clcr reported in patients receiving IV acyclovir, particularly following rapid (over <10 minutes) IV infusion.409
Abnormal urinalysis (increase in formed elements in urine sediment) and pain or pressure on urination reported rarely with IV acyclovir.409
Renal failure, resulting in death, has occurred.341 403 409
Possible precipitation of acyclovir in renal tubules, resulting in renal tubular damage and acute renal failure, when the solubility of free acyclovir in the collecting duct is exceeded or following rapid IV administration.409
Risk of adverse renal effects during IV therapy depends on degree of hydration, urine output, concomitant therapy (i.e., nephrotoxic drugs), preexisting renal disease, and rate of administration (see Rate of Administration under Dosage and Administration).409
Alterations in renal function during IV acyclovir therapy can progress to acute renal failure but generally are transient and resolve spontaneously or following improved hydration and electrolyte balance, dosage adjustment, or discontinuance of the drug.409
Hematologic Effects
Potentially fatal thrombotic thrombocytopenic purpura/hemolytic uremic syndrome reported in immunocompromised patients receiving acyclovir.403 409
General Precautions
Nervous System Effects
Possible encephalopathic effects (e.g., lethargy, obtundation, tremors, confusion, hallucinations, agitation, seizures, coma) in patients receiving IV acyclovir.409
Use with caution in patients with underlying neurologic abnormalities and in those with serious renal, hepatic, or electrolyte abnormalities or substantial hypoxia.409
Local Effects
Severe local inflammatory reactions, including tissue necrosis, have occurred following infusion of acyclovir into extravascular tissues.409
Sodium Content
Sodium salt of acyclovir contains 4.2 mEq of sodium per gram of acyclovir.409
Specific Populations
Pregnancy
Category B.403 409
CDC, AAP, and others state that oral acyclovir may be used during pregnancy to treat first episodes or severe recurrent episodes of genital herpes244 322 381 412 421 and IV acyclovir may be used during pregnancy to treat severe HSV infection (especially life-threatening disseminated infections).244 322 412 421 CDC and others also recommend acyclovir for treatment of varicella during pregnancy,412 415 particularly during the second and third trimesters.415
Lactation
Distributed into milk following oral or IV administration.251 308 403 409 421 Use with caution.403 409
Women with active herpetic lesions near or on the breast should refrain from breast-feeding.322
Pediatric Use
Safety and efficacy of oral acyclovir not established in children <2 years of age.403
Geriatric Use
For treatment of herpes zoster (shingles, zoster), no substantial differences in efficacy of oral acyclovir relative to younger adults, but duration of pain after healing may be longer in geriatric patients.403
Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently to IV acyclovir than younger adults.409
Select dosage with caution because of age-related decreases in renal function and potential for concomitant disease and drug therapy.409 Consider monitoring renal function.409
Possible increased incidence of adverse CNS effects (coma, confusion, hallucinations, somnolence), GI effects (nausea, vomiting), or diz
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