Acyclovir (Monograph)
Brand name: Zovirax
Drug class: Nucleosides and Nucleotides
Introduction
Antiviral; purine nucleoside analog derived from guanine.403 409
Uses for Acyclovir
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† [off-label] 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† [off-label] adults and children;322 381 418 generally ineffective or minimally effective for prevention of recurrence of herpes labialis† [off-label] in immunocompetent individuals.322 422
Treatment of eczema herpeticum† [off-label] in patients with a history of atopic dermatitis.223 224
Treatment of HSV keratitis† [off-label] 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
Acyclovir 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
IVImmunocompromised 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
IVHIV-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†
OralHIV-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†
OralChildren ≥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
IVImmunocompromised 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
IVNeonates 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†
OralHSV-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
IVHSV-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
OralChildren: 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
IVAdolescents 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
OralAdolescents: 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
OralAdolescents: 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)
OralImmunocompetent 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
IVImmunocompromised 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)
OralImmunocompetent 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
IVImmunocompetent 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
IVImmunocompromised 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†
OralHIV-infected adults: 200 mg 3 times daily or 400 mg twice daily.404
Treatment of Orolabial HSV Infections
Oral400 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†
OralHIV-infected adults: 400 mg 5 times daily.407 Long-term therapy may be required to prevent recurrence.407
Prophylaxis Against Recurrent Ocular HSV Disease†
OralImmunocompetent 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
IV10–15 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†
OralHSV-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
IVHSV-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
OralManufacturer 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
IVAdults 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†
Oral400 mg 5 times daily for 10 days or until clinical resolution occurs.305
Episodic Treatment of Recurrent Episodes of Genital Herpes
OralManufacturer 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
Oral400 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)
Oral20 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 OralHIV-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)
Oral800 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
IVHIV-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†
OralImmunocompetent 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 OralHIV-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†
OralImmunocompromised 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 Acyclovir
Contraindications
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
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 dizziness during oral acyclovir therapy compared with younger adults.403
Hepatic Impairment
Use with caution.a
Renal Impairment
Decreased acyclovir clearance.409 Increased risk of adverse renal and encephalopathic effects.409
Adjust dosage to prevent drug accumulation, decrease risk of toxicity, and maintain adequate plasma drug concentrations.316 (See Renal Impairment under Dosage and Administration.)
Common Adverse Effects
With oral therapy, nausea and/or vomiting and diarrhea.403 With IV therapy, local reactions at the injection site (inflammation, phlebitis).409
Drug Interactions
Nephrotoxic Agents
Potential pharmacodynamic interaction (increased risk of renal dysfunction and/or reversible CNS manifestations); use concomitantly with caution.403 409
Specific Drugs
Drug |
Interaction |
Comments |
---|---|---|
Interferon |
Additive or synergistic antiviral effect against HSV-1 in vitroa |
|
Methotrexate |
Manufacturer states that IV acyclovir should be used with caution in patients receiving intrathecal methotrexate409 |
|
Probenecid |
||
Zidovudine |
Neurotoxicity (profound drowsiness, lethargy) reported in at least 1 patient298 |
Monitor patients closely during concomitant therapy298 |
Acyclovir 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
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
Stability
Storage
Oral
Capsules and Tablets
Tight, light-resistant containers at 15–25°C.403
Suspension
15–25°C.403
Parenteral
Powder for IV Infusion
15–25°C.409 Use reconstituted solution within 12 hours.409 Refrigeration of this solution may cause a precipitate, which will redissolve at room temperature.409 Following dilution with infusion solution, use drug within 24 hours.409
Compatibility
Parenteral
Solution Compatibility
Bacteriostatic water for injection containing parabens should not be used to reconstitute acyclovir sodium powder; precipitation may occur.424
When diluted with >10% dextrose, a yellow discoloration may appear but does not affect potency.a
Compatible424 |
---|
Dextrose 5% and sodium chloride 0.2, 0.45, or 0.9% |
Dextrose 5% |
Lactated Ringer’s |
Sodium chloride 0.9% |
Drug Compatibility
Compatible |
---|
Fluconazole |
Incompatible |
Dobutamine HCl |
Dopamine HCl |
Variable |
Meropenem |
Compatible |
---|
Allopurinol sodium |
Amikacin sulfate |
Amphotericin B cholesteryl sulfate complex |
Ampicillin sodium |
Cefamandole nafate |
Cefazolin sodium |
Cefoperazone sodium |
Cefotaxime sodium |
Cefoxitin sodium |
Ceftazidime |
Ceftizoxime sodium |
Ceftriaxone sodium |
Cefuroxime sodium |
Chloramphenicol sodium succinate |
Cimetidine HCl |
Clindamycin phosphate |
Dexamethasone sodium phosphate |
Dimenhydrinate |
Diphenhydramine HCl |
Docetaxel |
Doxorubicin HCl liposome injection |
Doxycycline hyclate |
Erythromycin lactobionate |
Etoposide phosphate |
Famotidine |
Filgrastim |
Fluconazole |
Gatifloxacin |
Gentamicin sulfate |
Granisetron HCl |
Heparin sodium |
Hydrocortisone sodium succinate |
Hydromorphone HCl |
Imipenem–cilastatin sodium |
Linezolid |
Lorazepam |
Magnesium sulfate |
Melphalan HCl |
Methylprednisolone sodium succinate |
Metoclopramide HCl |
Metronidazole |
Milrinone lactate |
Multivitamins |
Nafcillin sodium |
Oxacillin sodium |
Paclitaxel |
Penicillin G potassium |
Pentobarbital sodium |
Perphenazine |
Piperacillin sodium |
Potassium chloride |
Propofol |
Ranitidine HCl |
Remifentanil HCl |
Sodium bicarbonate |
Tacrolimus |
Teniposide |
Theophylline |
Thiotepa |
Ticarcillin disodium |
Tobramycin sulfate |
Trimethoprim–sulfamethoxazole |
Vancomycin HCl |
Zidovudine |
Incompatible |
Amifostine |
Amsacrine |
Aztreonam |
Cefepime HCl |
Dobutamine HCl |
Dopamine HCl |
Fludarabine phosphate |
Foscarnet sodium |
Gemcitabine HCl |
Idarubicin HCl |
Levofloxacin |
Ondansetron HCl |
Piperacillin sodium–tazobactam sodium |
Sargramostim |
Tacrolimus |
Vinorelbine tartrate |
Variable |
Cisatracurium besylate |
Diltiazem HCl |
Meperidine HCl |
Meropenem |
Morphine sulfate |
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
-
Acyclovir-resistant HSV or VZV usually resistant to famciclovir and valacyclovir, but may be susceptible to foscarnet.244 381 413
Advice to Patients
-
Advise patients that acyclovir is not a cure for genital herpes and there are no data evaluating whether acyclovir prevents transmission of genital herpes to others.244
-
Importance of avoiding sexual contact with uninfected partners when genital lesions or prodromal symptoms are present, since there is a risk of infecting sexual partners.244 Genital herpes can be transmitted in the absence of symptoms.244
-
Importance of initiating treatment as soon as possible following onset of signs and symptoms.403 409
-
Advise patients receiving chronic suppressive therapy of the need for periodic reassessment of the continued need for acyclovir therapy.244 403
-
Importance of not exceeding the recommended dosage and duration of therapy.409
-
Importance of maintaining adequate hydration during treatment.403 409
-
Importance of contacting clinician if severe or troublesome adverse effects occur.403
-
Importance of informing clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs.403 409
-
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.403
-
Importance of advising patients of other important precautionary information. (See Cautions.)
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
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral |
Capsules |
200 mg* |
Acyclovir Capsules |
Actavis |
Zovirax (with parabens) |
GlaxoSmithKline |
|||
Suspension |
200 mg/5 mL* |
Acyclovir Suspension (with parabens) |
Actavis |
|
Zovirax (with glycerin, parabens, and sorbitol) |
GlaxoSmithKline |
|||
Tablets |
400 mg* |
Acyclovir Tablets |
Actavis |
|
Zovirax (with povidone) |
GlaxoSmithKline |
|||
800 mg* |
Acyclovir Tablets |
Actavis |
||
Zovirax (with povidone) |
GlaxoSmithKline |
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 |
|
Zovirax |
GlaxoSmithKline |
|||
1 g (of acyclovir) |
Acyclovir Sodium for Injection |
Abraxis |
||
Zovirax |
GlaxoSmithKline |
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 |
AHFS DI Essentials™. © Copyright 2025, Selected Revisions April 10, 2024. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.
References
Only references cited for selected revisions after 1984 are available electronically.
200. Saral R, Ambinder RF, Burns WH et al. Acyclovir prophylaxis against herpes simplex virus infection in patients with leukemia. Ann Intern Med. 1983; 99:773-6. https://pubmed.ncbi.nlm.nih.gov/6359995
201. Wade JC, Newton B, Flournoy N et al. Oral acyclovir for prevention of herpes simplex virus reactivation after marrow transplantation. Ann Intern Med. 1984; 100:823-8. https://pubmed.ncbi.nlm.nih.gov/6326632
202. Straus SE, Takiff HE, Seidlin M et al. Suppression of frequently recurring genital herpes: a placebo-controlled double-blind trial of oral acyclovir. N Engl J Med. 1984; 310:1545-50. https://pubmed.ncbi.nlm.nih.gov/6328297
203. Douglas JM, Critchlow C, Benedetti J et al. A double-blind study of oral acyclovir for suppression of recurrences of genital herpes simplex virus infection. N Engl J Med. 1984; 310:1551-6. https://pubmed.ncbi.nlm.nih.gov/6328298
204. Reichman RC, Badger GJ, Mertz GJ et al. Treatment of recurrent genital herpes simplex infections with oral acyclovir: a controlled trial. JAMA. 1984; 251:2103-7. https://pubmed.ncbi.nlm.nih.gov/6368877
205. Resnick L, Schleider-Kushner N, Horwitz SN et al. Remission of tumor-stage mycosis fungoides following intravenously administered acyclovir. JAMA. 1984; 251:1571-3. https://pubmed.ncbi.nlm.nih.gov/6700055
206. Nilsen AE, Aasen T, Halsos AM et al. Efficacy of oral acyclovir in the treatment of initial and recurrent genital herpes. Lancet. 1982; 2:571-3. https://pubmed.ncbi.nlm.nih.gov/6125728
207. Bryson YJ, Dillon M, Lovett M et al. Treatment of first episodes of genital herpes simplex virus infection with oral acyclovir: a randomized double-blind controlled trial in normal subjects. N Engl J Med. 1983; 308:916-21. https://pubmed.ncbi.nlm.nih.gov/6339923
208. Mertz GJ, Critchlow CW, Benedetti J et al. Double-blind placebo-controlled trial of oral acyclovir in first-episode genital herpes simplex virus infection. JAMA. 1984; 252:1147-51. https://pubmed.ncbi.nlm.nih.gov/6088819
209. Lagrew DC Jr, Furlow TG, Hager WD et al. Disseminated herpes simplex virus infection in pregnancy: successful treatment with acyclovir. JAMA. 1984; 252:2058-9. https://pubmed.ncbi.nlm.nih.gov/6481915
210. Mindel A, Weller IVD, Faherty A et al. Prophylactic oral acyclovir in recurrent genital herpes. Lancet. 1984; 2:57-9. https://pubmed.ncbi.nlm.nih.gov/6146006
211. Sköldenberg B, Forsgren M, Alestig K et al. Acyclovir versus vidarabine in herpes simplex encephalitis: randomised multicentre study in consecutive Swedish patients. Lancet. 1984; 2:707-11. https://pubmed.ncbi.nlm.nih.gov/6148470
212. Nicholson KG. Antiviral therapy: herpes simplex encephalitis, neonatal herpes infections, chronic hepatitis B. Lancet. 1984; 2:736-9. https://pubmed.ncbi.nlm.nih.gov/6207393
213. Fletcher C, Bean B. Evaluation of oral acyclovir therapy. Drug Intell Clin Pharm. 1985; 19:518-24. https://pubmed.ncbi.nlm.nih.gov/2992899
214. Shepp DH, Newton BA, Dandliker PS et al. Oral acyclovir therapy for mucocutaneous herpes simplex virus infections in immunocompromised marrow transplant recipients. Ann Intern Med. 1985; 102:783-5. https://pubmed.ncbi.nlm.nih.gov/2986508
215. Gluckman E, Lotsberg J, Devergie A et al. Prophylaxis of herpes infections after bone-marrow transplantation by oral acyclovir. Lancet. 1983; 2:706-8. https://pubmed.ncbi.nlm.nih.gov/6136841
216. Straus SE, Smith HA, Brickman C et al. Acyclovir for chronic mucocutaneous herpes simplex virus infection in immunosuppressed patients. Ann Intern Med. 1982; 96:270-7. https://pubmed.ncbi.nlm.nih.gov/7059087
217. Straus SE, Seidlin M, Takiff H et al. Oral acyclovir to suppress recurring herpes simplex virus infections in immunodeficient patients. Ann Intern Med. 1984; 100:522-4. https://pubmed.ncbi.nlm.nih.gov/6703544
218. Anderson H, Scarffe JH, Sutton RNP et al. Oral acyclovir prophylaxis against herpes simplex virus in non-Hodgkin lymphoma and acute lymphoblastic leukaemia patients receiving remission induction chemotherapy: a randomised double blind, placebo controlled trial. Br J Cancer. 1984; 50:45-9. https://pubmed.ncbi.nlm.nih.gov/6378236 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1976928/
219. Gnann JW. Crumpacker CS, Lalezari JP et al. Sorivudine versus acyclovir for treatment of dermatomal herpes zoster in human immunodeficiency virus-infected patients: results of a randomized, controlled clinical trial. Antimicrob Agents Chemother. 1998; 42:1139-45. https://pubmed.ncbi.nlm.nih.gov/9593141 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC105759/
220. Saral R, Burns WH, Laskin OL et al. Acyclovir prophylaxis of herpes-simplex-virus infections: a randomized, double-blind, controlled trial in bone-marrow-transplant recipients. N Engl J Med. 1981; 305:63-7. https://pubmed.ncbi.nlm.nih.gov/6264292
221. Hann IM, Prentice HG, Blacklock HA et al. Acyclovir prophylaxis against herpes virus infections in severely immunocompromised patients: randomised double blind trial. BMJ. 1983; 287:384-8. https://pubmed.ncbi.nlm.nih.gov/6307464 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1548921/
223. Woolfson H. Oral acyclovir in eczema herpeticum. BMJ. 1984; 288:531-2. https://pubmed.ncbi.nlm.nih.gov/6421367 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1444574/
224. Swart RN, Vermeer BJ, Van Der Meer JW et al. Treatment of eczema herpeticum with acyclovir. Arch Dermatol. 1983; 119:13-6. https://pubmed.ncbi.nlm.nih.gov/6849557
225. Trying S, Belanger R, Bezwoda W et al. A randomized, double-blind trial of famciclovir versus acyclovir for the treatment of localized dermatomal herpes zoster in immunocompromised patients. Cancer Invest. 2001; 19:13-22. https://pubmed.ncbi.nlm.nih.gov/11291551
226. Straus SE, Rooney JF, Sever JL et al. Herpes simplex virus infection: biology, treatment, and prevention. Ann Intern Med. 1985; 103:404-19. https://pubmed.ncbi.nlm.nih.gov/2411179
227. Peterslund NA, Esmann V, Ipsen J et al. Oral and intravenous acyclovir are equally effective in herpes zoster. J Antimicrob Chemother. 1984; 14:185-9. https://pubmed.ncbi.nlm.nih.gov/6389470
228. McKendrick MW, Care C, Burke C et al. Oral acyclovir in herpes zoster. J Antimicrob Chemother. 1984; 14:661-5. https://pubmed.ncbi.nlm.nih.gov/6394572
229. Novelli VM, Marshall WC, Yeo J et al. Acyclovir administered perorally in immunocompromised children with varicella-zoster infections. J Infect Dis. 1984; 149:478. https://pubmed.ncbi.nlm.nih.gov/6715905
230. Hanto DW, Frizzera G, Gajl-Peczalska KJ et al. Epstein-Barr virus-induced B-cell lymphoma after renal transplantation: acyclovir therapy and transition from polyclonal to monoclonal proliferation. N Engl J Med. 1982; 306:913-8. https://pubmed.ncbi.nlm.nih.gov/6278307
231. Hanto DW, Gajl-Peczalska KJ, Frizzera G et al. Epstein-Barr virus (EBV) induced polyclonal and monoclonal B-cell lymphoproliferative diseases occurring after renal transplantation: clinical, pathologic, and virologic findings and implications for therapy. Ann Surg. 1983; 198:356-67. https://pubmed.ncbi.nlm.nih.gov/6311121 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1353308/
232. Van Dyke RB, Connor JD, Wyborny C et al. Pharmacokinetics of orally administered acyclovir in patients with herpes progenitalis. Am J Med. 1982; 73(Suppl 1A):172-5. https://pubmed.ncbi.nlm.nih.gov/7102701
233. de Miranda P, Blum MR. Pharmacokinetics of acyclovir after intravenous and oral administration. J Antimicrob Chemother. 1983; 12(Suppl B):29-37. https://pubmed.ncbi.nlm.nih.gov/6355048
234. Tucker WE. Preclinical toxicology profile of acyclovir: an overview. Am J Med. 1982; 73(Suppl 1A):27-30. https://pubmed.ncbi.nlm.nih.gov/7048916
235. VanLandingham KE, Marsteller HB, Ross GW et al. Relapse of herpes simplex encephalitis after conventional acyclovir therapy. JAMA. 1988; 259:1051-1. https://pubmed.ncbi.nlm.nih.gov/3339802
236. Rothman AL, Cheeseman SH, Lehrman SN et al. Herpes simplex encephalitis in a patient with lymphoma: relapse following acyclovir therapy. JAMA. 1988; 259:1056-7. https://pubmed.ncbi.nlm.nih.gov/3276941
238. Nyerges G, Meszner Z, Gyarmati E et al. Acyclovir prevents dissemination of varicella in immunocompromised children. J Infect Dis. 1988; 157:309-13. https://pubmed.ncbi.nlm.nih.gov/2826611
239. Balfour HH Jr, Kelley JM, Suarez CS et al. Acyclovir treatment of varicella in otherwise healthy children. J Pediatr. 1990; 116:633-9. https://pubmed.ncbi.nlm.nih.gov/2156984
240. Al-Nakib W, Al-Kandari S, El-Khalik DMA et al. A randomized controlled study of intravenous acyclovir (Zovirax) against placebo in adults with chickenpox. J Infect. 1983; 6(Suppl 1):49-56.
241. Jacobson MA, Berger TG, Fikrig S et al. Acyclovir-resistant varicella zoster virus infection after chronic oral acyclovir therapy in patients with the acquired immunodeficiency syndrome (AIDS). Ann Intern Med. 1990; 112:187-91. https://pubmed.ncbi.nlm.nih.gov/2297195
242. Thin RN, Jeffries DJ, Taylor PK et al. Recurrent genital herpes suppressed by oral acyclovir: a multicentre double blind trial. J Antimicrob Chemother. 1985; 16:219-26. https://pubmed.ncbi.nlm.nih.gov/3905750
243. Salo OP, Lassus A, Hovi T et al. Double-blind placebo-controlled trial of oral acyclovir in recurrent genital herpes. Eur J Sex Transmit Dis. 1983; 1:95-8.
244. Centers for Disease Control and Prevention. Sexually transmitted diseases treatment guidelines, 2006. MMWR Recomm Rep. 2006; 55(RR-11):1-95.
245. Greffe BS, Dooley SL, Deddish RB et al. Transplacental passage of acyclovir. J Pediatr. 1986; 108:1020-1. https://pubmed.ncbi.nlm.nih.gov/3012053
246. Whitley RJ, Alford CA, Hirsch MS et al. Vidarabine versus acyclovir therapy in herpes simplex encephalitis. N Engl J Med. 1986; 314:144-9. https://pubmed.ncbi.nlm.nih.gov/3001520
248. Corey L, Spear PG. Infections with herpes simplex viruses (second of two parts). N Engl J Med. 1986; 314:749-57. https://pubmed.ncbi.nlm.nih.gov/3005859
249. Shepp DH, Dandliker PS, Meyers JD. Treatment of varicella-zoster virus infection in severely immunocompromised patients: a randomized comparison of acyclovir and vidarabine. N Engl J Med. 1986; 314:208-12. https://pubmed.ncbi.nlm.nih.gov/3001523
250. Pottage JC, Kessler HA, Goodrich JM et al. In vitro activity of ketoconazole against herpes simplex virus. Antimicrob Agents Chemother. 1986; 30:215-9. https://pubmed.ncbi.nlm.nih.gov/3021048 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC180521/
251. Lau RJ, Emery MG, Galinsky RE. Unexpected accumulation of acyclovir in breast milk with estimation of infant exposure. Obstet Gynecol. 1987; 69:468-71. https://pubmed.ncbi.nlm.nih.gov/3808527
252. Brundage DM, Fletcher CV, Chinnock B et al. Acyclovir disposition in critically ill patients with herpes virus infections on continuous peritoneal dialysis. Drug Intell Clin Pharm. 1985; 19:453.
253. Seth SK, Visconti JA, Hebert LA et al. Acyclovir pharmacokinetics in a patient on continuous ambulatory peritoneal dialysis. Clin Pharm. 1985; 4:320-2. https://pubmed.ncbi.nlm.nih.gov/4006396
254. Englund JA, Fletcher CV, Johnson D et al. Effect of blood exchange on acyclovir clearance in an infant with neonatal herpes. J Pediatr. 1987; 110:151-3. https://pubmed.ncbi.nlm.nih.gov/3794878
255. Steele RW, Keeney RE, Bradsher RW et al. Treatment of varicella-zoster meningoencephalitis with acyclovir: demonstration of virus in cerebrospinal fluid by electron microscopy. Am J Clin Pathol. 1983; 80:57-60. https://pubmed.ncbi.nlm.nih.gov/6305186
256. Ehrensaft DV, Safani MM. Acyclovir and disseminated varicella zoster and encephalitis. Ann Intern Med. 1985; 102:421. https://pubmed.ncbi.nlm.nih.gov/3970498
257. Cheesbrough JS, Finch RG, Ward MJ. A case of herpes zoster associated encephalitis with rapid response to acyclovir. Postgrad Med J. 1985; 61:145-6. https://pubmed.ncbi.nlm.nih.gov/3983042 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2418175/
258. Bowman RV, Lythall DA, De Wytt CN. A case of herpes zoster associated encephalitis treated with acyclovir. Aust N Z J Med. 1985; 15:43-4. https://pubmed.ncbi.nlm.nih.gov/2988489
259. Whyte MKB, Ind PW. Effectiveness of intravenous acyclovir in immunocompetent patient with herpes zoster encephalitis. BMJ. 1986; 293:1536-7. https://pubmed.ncbi.nlm.nih.gov/3099946 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1342310/
260. Johns DR, Gress DR. Rapid response to acyclovir in herpes zoster-associated encephalitis. Am J Med. 1987; 82:560-2. https://pubmed.ncbi.nlm.nih.gov/3826110
261. McKendrick MW, McGill JI, White JE et al. Oral acyclovir in acute herpes zoster. BMJ. 1986; 293:1529-32. https://pubmed.ncbi.nlm.nih.gov/3099943 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1342307/
262. Andersson J, Britton S, Ernberg I et al. Effect of acyclovir on infectious mononucleosis: a double-blind, placebo-controlled study. J Infect Dis. 1986; 153:283-90. https://pubmed.ncbi.nlm.nih.gov/3003206
263. Grover L, Kane J, Kravitz J et al. Systemic acyclovir in pregnancy: a case report. Obstet Gynecol. 1985; 65:284-7. https://pubmed.ncbi.nlm.nih.gov/4038548
264. Leen CLS, Mandal BK, Ellis ME et al. Acyclovir and pregnancy. BMJ. 1987; 294:308. https://pubmed.ncbi.nlm.nih.gov/3101853 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1245311/
265. Andrews EB, Tilson HH, Hurn BAL et al. Acyclovir in pregnancy registry: an observational epidemiologic approach. Am J Med. 1988; 85(Suppl 2A):123-8.
266. Douglas JM Jr, Davis LG, Remington ML et al. A double-blind, placebo-controlled trial of the effect of chronically administered oral acyclovir on sperm production in men with frequently recurring genital herpes. J Infect Dis. 1988; 157:588-93. https://pubmed.ncbi.nlm.nih.gov/2830348
267. Straus SE, Dale JK, Tobi M et al. Acyclovir treatment of the chronic fatigue syndrome: lack of efficacy in a placebo-controlled trial. N Engl J Med. 1988; 319:1692-8. https://pubmed.ncbi.nlm.nih.gov/2849717
268. Swartz MN. The chronic fatigue syndrome—one entity or many? N Engl J Med. 1988; 319:1726-8. Editorial.
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270. Pagano JS, Sixbey JW, Lin JC. Acyclovir and Epstein-Barr virus infection. J Antimicrob Chemother. 1983; 12(Suppl B): 113-21. https://pubmed.ncbi.nlm.nih.gov/6313591
271. Andersson J, Skoldenberg B, Ernberg I et al. Acyclovir treatment in primary Epstein-Barr virus infection: a double-blind placebo-controlled study. Scand J Infect Dis Suppl. 1985; 47:107-15. https://pubmed.ncbi.nlm.nih.gov/3006226
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274. Resnick L, Herbst JS, Ablashi DV et al. Regression of oral hairy leukoplakia after orally administered acyclovir therapy. JAMA. 1988; 259:384-8. https://pubmed.ncbi.nlm.nih.gov/2826830
275. Schooley RT, Carey RW, Miller G et al. Chronic Epstein-Barr virus associated with fever and interstitial pneumonitis: clinical and serologic features and response to antiviral chemotherapy. Ann Intern Med. 1986; 104:636-43. https://pubmed.ncbi.nlm.nih.gov/3008616
276. Sullivan JL, Medveczky P, Forman SJ et al. Epstein-Barr-virus induced lymphoproliferation: implications for antiviral chemotherapy. N Engl J Med. 1984; 311:1163-7. https://pubmed.ncbi.nlm.nih.gov/6090906
277. Shepp DH, Dandliker PS, Meyers JD et al. Current therapy of varicella zoster virus infection in immunocompromised patients: a comparison of acyclovir and vidarabine. Am J Med. 1988; 85(Suppl 2A):96-8. https://pubmed.ncbi.nlm.nih.gov/3044102
278. Nyerges G, Meszner Z. Treatment of chickenpox in immunocompromised children. Am J Med. 1988; 85(Suppl 2A):94-5. https://pubmed.ncbi.nlm.nih.gov/3044101
279. Balfour HH Jr. Varicella zoster virus infections in immunocompromised hosts: a review of the natural history and management. Am J Med. 1988; 85(Suppl 2A):68-73. https://pubmed.ncbi.nlm.nih.gov/3044096
281. Cobo LM, Foulks GN, Liesegang T et al. Oral acyclovir in the treatment of acute herpes zoster ophthalmicus. Ophthalmology. 1986; 93:763-70. https://pubmed.ncbi.nlm.nih.gov/3488532
282. Cobo M. Reduction of ocular complications of herpes zoster ophthalmicus by oral acyclovir. Am J Med. 1988; 85(Suppl 2A):90-3. https://pubmed.ncbi.nlm.nih.gov/3044100
283. Wassilew SW, Reimlinger S, Nasemann T et al. Oral acyclovir for herpes zoster: a double-blind controlled trial in normal subjects. Br J Dermatol. 1987; 117:495-501. https://pubmed.ncbi.nlm.nih.gov/3314973
284. Huff JC, Bean B, Balfour HH Jr et al. Therapy of herpes zoster with oral acyclovir. Am J Med. 1988; 85(Suppl 2A):84-9. https://pubmed.ncbi.nlm.nih.gov/3044099
285. Wood MJ, Ogan PH, McKendrick MW et al. Efficacy of oral acyclovir treatment of acute herpes zoster. Am J Med. 1988; 85(Suppl 2A):79-83. https://pubmed.ncbi.nlm.nih.gov/3044098
286. Collins GE (Burroughs Wellcome, Research Triangle Park, NC): Personal communication; 1988 Mar 28.
287. Pahwa S, Biron K, Lim W et al. Continuous varicella-zoster infection associated with acyclovir resistance in a child with AIDS. JAMA. 1988; 260:2879-82. https://pubmed.ncbi.nlm.nih.gov/3184352
288. Collins P. Viral sensitivity following the introduction of acyclovir. Am J Med. 1988; 85(Suppl 2A):129-34. https://pubmed.ncbi.nlm.nih.gov/2841855
289. Cole NL, Balfour HH Jr. Varicella-zoster virus does not become more resistant to acyclovir during therapy. J Infect Dis. 1986; 153:605-8. https://pubmed.ncbi.nlm.nih.gov/3005428
290. Stahlmann R, Klug S, Lewandowski C et al. Teratogenicity of acyclovir in rats. Infection. 1987; 15:261-2. https://pubmed.ncbi.nlm.nih.gov/3666969
291. Chahoud I, Stahlmann R, Bochert G et al. Gross-structural defects in rats after acyclovir application on day 10 of gestation. Arch Toxicol. 1988; 62:8-14. https://pubmed.ncbi.nlm.nih.gov/3190462
292. Stahlmann R, Klug S, Lewandowski C et al. Prenatal toxicity of acyclovir. Arch Toxicol. 1988; 61:468-79. https://pubmed.ncbi.nlm.nih.gov/3190444
293. Erlich KS, Mills J, Chatis P et al. Acyclovir-resistant herpes simplex virus infections in patients with acquired immunodeficiency syndrome. N Engl J Med. 1989; 320:293-6. https://pubmed.ncbi.nlm.nih.gov/2536136
294. Hirsch MS, Schooley RT. Resistance to antiviral drugs: the end of innocence. N Engl J Med. 1989; 320:313-4. https://pubmed.ncbi.nlm.nih.gov/2536138
296. National Institutes of Health. Consensus development conference statement: oral complications of cancer therapies: diagnosis, prevention, and treatment. 1989; 7(7):1-12.
298. Bach MC. Possible drug interaction during therapy with azidothymidine and acyclovir for AIDS. N Engl J Med. 1987; 316:547. https://pubmed.ncbi.nlm.nih.gov/3468354
304. Fischl MA, Richman DD, Grieco MH et al. The efficacy of azidothymidine (AZT) in the treatment of patients with AIDS and AIDS-related complex. N Engl J Med. 1987; 317:185-91. https://pubmed.ncbi.nlm.nih.gov/3299089
305. Rompalo AM, Mertz GJ, Davis G et al. Oral acyclovir for treatment of first-episode herpes simplex proctitis. JAMA. 1988; 259:2879-82. https://pubmed.ncbi.nlm.nih.gov/3367455
306. Bubley GJ, Chapman B, Chapman SK et al. Effect of acyclovir on radiation- and chemotherapy-induced mouth lesions. Antimicrob Agents Chemother. 1989; 33:862-5. https://pubmed.ncbi.nlm.nih.gov/2669626 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC284246/
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