Acyclovir is an acyclic analogue of 2'-deoxyguanosine.

Antiviral Activity:

Acyclovir has activity against herpesviruses.

Mechanism of Action:

Acyclovir is converted to its triphosphate form, acyclovir triphosphate (ACV-TP), which competitively inhibits viral DNA polymerase, incorporates into and terminates the growing viral DNA chain, and inactivates the viral DNA polymerase.

Mechanism of Resistance:

The primary mechanism of resistance to acyclovir is related to viral thymidine kinase (TK) and DNA polymerase mutations.


No relationship has been established between the effective in vitro and in vivo concentrations of acyclovir, although there is a significant correlation between the ID50 of acyclovir for the virus and the clinical response.


Acyclovir is slowly and poorly absorbed from the gastrointestinal tract and bioavailability decreases with increasing dose. Acyclovir is widely distributed into tissues and body fluids. Plasma protein binding is relatively low at 9 to 24%. Renal excretion is the major route of elimination of acyclovir.

Adverse Effects:

Most common with oral acyclovir are lightheadedness, headache, diarrhea, nausea, vomiting and abdominal pain. The most common effects associated with parenteral acyclovir are lightheadedness and anorexia. The most common adverse effects associated with topical acyclovir are mild pain, burning and stinging.


Capsule 200mg

Cream 5%

Ointment 5%
Oral Suspension 25mg/ml, 50mg/ml, 200mg/5ml

Powder for Injection 500mg

Tablet 400mg, 800mg

HSV infections of skin and mucous membranes including initial and recurrent genital herpes

Adult:      200 mg po 5 x daily for 5 days

                400 mg po 5 x daily or 5 mg/kg IV q8h for 5 days in severely infected or immunocompromised patients

Initial genital: 400 mg po tid x 7 – 10 days or 200 mg po 5 x daily x 7 – 10 days

Recurrent genital: 400 mg po tid x 5 days or 200 mg po 5 x daily x 5 days or 800 mg po bid x 5 days

Pediatric: Age ≥ 2 years = adult dose

                  Age < 2 years = half adult dose

                  Neonates and infants = 20 mg/kg IV q8h for 14 days (21 days for disseminated or CNS infection)

Episodic HSV treatment in HIV-infected patients

Adult:      400 mg po tid x 5 – 10 days or 200 mg 5 times daily for 5 – 10 days

Pediatric: No data

Suppression of recurrent HSV in immunocompetent patients

Adult:      400 mg bid

Pediatric: No data

Prophylaxis of HSV in immunocompromised patients

Adult:      400 – 800 mg po 2 or 3 times daily

                5 mg/kg IV q8h in severely immunocompromised (i.e. bone marrow transplant) patients or those with impaired absorption                 from gut

Pediatric: Age ≥ 2 years = adult dose

Age < 2 years = half adult dose

Herpes encephalitis

Adult:      10 mg/kg IV q8h

Pediatric: 500 mg/m2 IV q8h

VZV infections including varicella (chicken pox) and herpes zoster (shingles)

Adult:      800 mg po 5 x daily for 7 days

                10 mg/kg IV q8h in severely immunocompromised patients or those with impaired absorption from gut (treat for 2 – 7 days                 or until clinical improvement, followed by po therapy to complete 10 days of total treatment)

Pediatric: Varicella infections:

                Age > 6 years = 800 mg po 4 x daily

                Age 2 – 5 years = 400 mg po 4 x daily

                Age < 2 years = 200 mg po 4 x daily

                Continue treatment for 5 days

                Alternatively: calculate dosing at 20 mg/kg po (max 800 mg) 4 x daily

                IV dose = 250 mg/m2 q8h

                Immunocompromised children = 500 mg/m2 IV q8h

                No data on treatment of herpes zoster in immunocompetent children

Disease state based dosing:

Renal Impairment: Oral tablets for Herpes simplex (HSV) or Varicella Zoster (VZV):

                               CrCl 10-29ml/min (VZV only) give 800mg PO q8h

                               CrCl < 10ml/min (VZV) give 800mg PO q12h

                               CrCl < 10ml/min (HSV) give 200mg PO q12h

Intravenous dosing for HSV: CrCl 25-50ml/min give 5mg/kg IV q12h

                               CrCl: 10-25ml/min 5mg/kg IV q24h

                               CrCl: < 10ml/min 2.5mg/kg IV q24h

Intravenous dosing for VZV: CrCl 25-50ml/min give 10mg/kg IV q12h

                       CrCl: 10-25ml/min 10mg/kg IV q24h

           CrCl: < 10ml/min 5mg/kg IV q24h

Hepatic Impairment: No dose adjustment is necessary

Dosing during Continuous Renal Replacement Therapy

CVVH (Continuous venovenous hemofiltration): 5-7.5mg/kg q24h

CVVHD (Continuous venovenous hemodialysis): 5-7.5mg/kg q24h

CVVHDF (Continuous venovenous hemodiafiltration) 5-7.5mg/kg q24h

Note: CVVH is mainly for fluid removal alone. Many institutions will employ more CVVHD or CVVHDF which combine dialysis with fluid removal.

Drug Interactions:

Use caution when combining acyclovir with potentially nephrotoxic agents.

Pregnancy: Category B: No evidence of risk in humans but studies inadequate.

Monitoring Requirements:

Baseline serum creatinine/BUN

Brand names/Manufacturer:

Zovirax®/Glaxo Wellcome Inc, Glaxo Wellcome Division Smithkline Beecham Corp, Biovail Pharmaceuticals Inc Acyclovir/STADA Pharmaceuticals Inc, Akyma Pharmaceuticals, Ranbaxy Pharmaceuticals Inc, Genpharm Inc,  Mova Pharmaceuticals Corp, Par Pharmaceutical Inc, Apotheca Inc, Watson Pharmaceuticals Inc, Mylan Pharmaceuticals Inc, Purepac Pharmaceutical Co, Goldline Laboratories Inc/IVAX Pharmaceuticals, Ivax Corporation, Ivax Pharmaceuticals Inc, Teva Pharmaceuticals USA Inc, American Pharmaceutical Partners Inc (APP), Mayne Pharma (USA) Inc, Meridian Medical Technologies Inc, Bedford Laboratories, Alpharma USPD Inc, Stason Pharmaceuticals Inc.