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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

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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
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

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 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

Interactions for Zovirax

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

Clinical importance unknown;a use with caution409

Methotrexate

Manufacturer states that IV acyclovir should be used with caution in patients receiving intrathecal methotrexate409

Probenecid

Decreased renal clearance of acyclovir403 409

Zidovudine

Neurotoxicity (profound drowsiness, lethargy) reported in at least 1 patient298

Monitor patients closely during concomitant therapy298

Zovirax 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

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

For information on systemic interactions resulting from concomitant use, see Interactions.

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
Admixture Compatibility424

Compatible

Fluconazole

Incompatible

Dobutamine HCl

Dopamine HCl

Variable

Meropenem

Y-site Injection Compatibility424

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

  • 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

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.

* 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

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Acyclovir 200MG Capsules (CARLSBAD TECHNOLOGIES): 30/$14.99 or 90/$21.97

Acyclovir 200MG/5ML Suspension (HI-TECH): 473/$126.00 or 1419/$356.01

Acyclovir 400MG Tablets (CARLSBAD TECHNOLOGIES): 60/$30.99 or 180/$74.99

Acyclovir 800MG Tablets (TEVA PHARMACEUTICALS USA): 30/$24.99 or 90/$55.97

Zovirax 200MG Capsules (GLAXO SMITH KLINE): 30/$96.99 or 90/$279.97

Zovirax 400MG Tablets (GLAXO SMITH KLINE): 60/$361.98 or 180/$1,057.02

Zovirax 800MG Tablets (GLAXO SMITH KLINE): 30/$336.31 or 90/$1,008.93

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions July 1, 2007. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

† 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. [IDIS 179199] [PubMed 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. [IDIS 186242] [PubMed 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. [IDIS 186143] [PubMed 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. [IDIS 186144] [PubMed 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. [IDIS 183907] [PubMed 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. [IDIS 182344] [PubMed 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. [IDIS 158894] [PubMed 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. [IDIS 169254] [PubMed 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. [IDIS 189357] [PubMed 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. [IDIS 191370] [PubMed 6481915]

210. Mindel A, Weller IVD, Faherty A et al. Prophylactic oral acyclovir in recurrent genital herpes. Lancet. 1984; 2:57-9. [IDIS 188030] [PubMed 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. [IDIS 191472] [PubMed 6148470]

212. Nicholson KG. Antiviral therapy: herpes simplex encephalitis, neonatal herpes infections, chronic hepatitis B. Lancet. 1984; 2:736-9. [IDIS 191479] [PubMed 6207393]

213. Fletcher C, Bean B. Evaluation of oral acyclovir therapy. Drug Intell Clin Pharm. 1985; 19:518-24. [IDIS 202156] [PubMed 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. [IDIS 200719] [PubMed 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. [IDIS 176532] [PubMed 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. [IDIS 146174] [PubMed 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. [IDIS 183829] [PubMed 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. [PubMed 6378236]

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. [IDIS 404906] [PubMed 9593141]

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. [IDIS 133355] [PubMed 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. [IDIS 174535] [PubMed 6307464]

223. Woolfson H. Oral acyclovir in eczema herpeticum. BMJ. 1984; 288:531-2. [IDIS 182115] [PubMed 6421367]

224. Swart RN, Vermeer BJ, Van Der Meer JW et al. Treatment of eczema herpeticum with acyclovir. Arch Dermatol. 1983; 119:13-6. [IDIS 164156] [PubMed 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. [PubMed 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. [IDIS 205826] [PubMed 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. [PubMed 6389470]

228. McKendrick MW, Care C, Burke C et al. Oral acyclovir in herpes zoster. J Antimicrob Chemother. 1984; 14:661-5. [PubMed 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. [IDIS 184669] [PubMed 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. [IDIS 147754] [PubMed 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. [PubMed 6311121]

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. [IDIS 154029] [PubMed 7102701]

233. de Miranda P, Blum MR. Pharmacokinetics of acyclovir after intravenous and oral administration. J Antimicrob Chemother. 1983; 12(Suppl B):29-37. [PubMed 6355048]

234. Tucker WE. Preclinical toxicology profile of acyclovir: an overview. Am J Med. 1982; 73(Suppl 1A):27-30. [PubMed 7048916]

235. VanLandingham KE, Marsteller HB, Ross GW et al. Relapse of herpes simplex encephalitis after conventional acyclovir therapy. JAMA. 1988; 259:1051-1. [IDIS 238050] [PubMed 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. [IDIS 238052] [PubMed 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. [IDIS 238855] [PubMed 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. [IDIS 265253] [PubMed 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. [IDIS 263424] [PubMed 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. [PubMed 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. [IDIS 217560] [PubMed 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. [IDIS 209631] [PubMed 3001520]

248. Corey L, Spear PG. Infections with herpes simplex viruses (second of two parts). N Engl J Med. 1986; 314:749-57. [IDIS 212038] [PubMed 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. [IDIS 209575] [PubMed 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. [IDIS 220405] [PubMed 3021048]

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. [IDIS 226518] [PubMed 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. [IDIS 200248] [PubMed 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. [IDIS 225710] [PubMed 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. [IDIS 172942] [PubMed 6305186]

256. Ehrensaft DV, Safani MM. Acyclovir and disseminated varicella zoster and encephalitis. Ann Intern Med. 1985; 102:421. [IDIS 196971] [PubMed 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. [PubMed 3983042]

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. [PubMed 2988489]

259. Whyte MKB, Ind PW. Effectiveness of intravenous acyclovir in immunocompetent patient with herpes zoster encephalitis. BMJ. 1986; 293:1536-7. [IDIS 224664] [PubMed 3099946]

260. Johns DR, Gress DR. Rapid response to acyclovir in herpes zoster-associated encephalitis. Am J Med. 1987; 82:560-2. [IDIS 226743] [PubMed 3826110]

261. McKendrick MW, McGill JI, White JE et al. Oral acyclovir in acute herpes zoster. BMJ. 1986; 293:1529-32. [IDIS 224662] [PubMed 3099943]

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. [IDIS 211053] [PubMed 3003206]

263. Grover L, Kane J, Kravitz J et al. Systemic acyclovir in pregnancy: a case report. Obstet Gynecol. 1985; 65:284-7. [IDIS 196511] [PubMed 4038548]

264. Leen CLS, Mandal BK, Ellis ME et al. Acyclovir and pregnancy. BMJ. 1987; 294:308. [IDIS 225799] [PubMed 3101853]

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. [IDIS 239523] [PubMed 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. [IDIS 248809] [PubMed 2849717]

268. Swartz MN. The chronic fatigue syndrome—one entity or many? N Engl J Med. 1988; 319:1726-8. Editorial.

269. Holmes GP, Kaplan JE, Gantz NM et al. Chronic fatigue syndrome: a working case definition. Ann Intern Med. 1988; 108:387-9. [PubMed 2829679]

270. Pagano JS, Sixbey JW, Lin JC. Acyclovir and Epstein-Barr virus infection. J Antimicrob Chemother. 1983; 12(Suppl B): 113-21. [PubMed 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. [PubMed 3006226]

272. Andersson J, Ernberg I. Management of Epstein-Barr virus infections. Am J Med. 1988; 85(Suppl 2A):107-15. [IDIS 247140] [PubMed 2841854]

273. Hanto DW, Najarian JS. Advances in the diagnosis and treatment of EBV-associated lymphoproliferative diseases in immunocompromised hosts. J Surg Oncol. 1985; 30:215-20. [PubMed 3001429]

274. Resnick L, Herbst JS, Ablashi DV et al. Regression of oral hairy leukoplakia after orally administered acyclovir therapy. JAMA. 1988; 259:384-8. [IDIS 236672] [PubMed 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. [IDIS 215745] [PubMed 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. [IDIS 191910] [PubMed 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. [IDIS 247137] [PubMed 3044102]

278. Nyerges G, Meszner Z. Treatment of chickenpox in immunocompromised children. Am J Med. 1988; 85(Suppl 2A):94-5. [IDIS 247136] [PubMed 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. [IDIS 247131] [PubMed 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. [PubMed 3488532]

282. Cobo M. Reduction of ocular complications of herpes zoster ophthalmicus by oral acyclovir. Am J Med. 1988; 85(Suppl 2A):90-3. [IDIS 247135] [PubMed 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. [IDIS 234623] [PubMed 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. [IDIS 247134] [PubMed 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. [IDIS 247133] [PubMed 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. [IDIS 247411] [PubMed 3184352]

288. Collins P. Viral sensitivity following the introduction of acyclovir. Am J Med. 1988; 85(Suppl 2A):129-34. [IDIS 247143] [PubMed 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. [IDIS 212580] [PubMed 3005428]

290. Stahlmann R, Klug S, Lewandowski C et al. Teratogenicity of acyclovir in rats. Infection. 1987; 15:261-2. [PubMed 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. [PubMed 3190462]

292. Stahlmann R, Klug S, Lewandowski C et al. Prenatal toxicity of acyclovir. Arch Toxicol. 1988; 61:468-79. [PubMed 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. [IDIS 250261] [PubMed 2536136]

294. Hirsch MS, Schooley RT. Resistance to antiviral drugs: the end of innocence. N Engl J Med. 1989; 320:313-4. [IDIS 250263] [PubMed 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. [IDIS 225771] [PubMed 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. [IDIS 231925] [PubMed 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. [IDIS 241515] [PubMed 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. [IDIS 255716] [PubMed 2669626]

307. Glaxo Wellcome. Zovirax (acyclovir) capsules, tablets, and suspension prescribing information. In: Physicians' desk reference. 50th ed. Montvale, NJ: Medical Economics Company Inc; 1996:1219-22.

308. Meyer LJ, de Miranda P, Sheth N et al. Acyclovir in human breast milk. Am J Obstet Gynecol. 1988; 158:586-8. [IDIS 310448] [PubMed 3348321]

309. Morton P, Thomson AN. Oral acyclovir in the treatment of herpes zoster in general practice. N Z Med J. 1989; 102:93-5. [IDIS 254523] [PubMed 2648213]

311. Gulliford MC, Chandrasekera CP, Cooper RA et al. Acyclovir treatment of herpes simplex encephalitis: experience in a district hospital. Postgrad Med J. 1987; 63:1037-41. [PubMed 3451230]

313. Anon. Drugs for sexually transmitted infections. Treat Guidel Med Lett. 2004; 2:67-74. [PubMed 15529116]

314. Prober CG, Gershon AA, Grose C et al. Consensus: Varicella-zoster infections in pregnancy and the perinatal period. Pediatr Infect Dis J. 1990; 9:865-9. [PubMed 2277741]

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316. Burroughs Wellcome Co. Research Triangle Park, NC: Personal communication.

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