Acyclovir
Mechanism :
Acyclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against herpes simplex virus types 1 (HSV-1), 2 (HSV-2), and varicella-zoster virus (VZV).
The inhibitory activity of acyclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. TK converts acyclovir into acyclovir monophosphate, a nucleotide analogue. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by several cellular enzymes. Acyclovir triphosphate stops replication of herpes viral DNA. This is accomplished in 3 ways: 1) competitive inhibition of viral DNA polymerase, 2) incorporation into and termination of the growing viral DNA chain, and 3) inactivation of the viral DNA polymerase.
Indication :
- Chicken pox
- Herpes zoster
- Herpes encephalitis
- Herpes labialis and Herpes genitalis
- Prophylaxis of Herpes simplex in the immunocompromised
Contraindications :
Contraindicated in patients hypersensitive to acyclovir.
In high doses, polyuric renal failure has occurred therefore adequate hydration should be maintained to prevent dehydration.
Dosing :
Neonatal herpes Simplex virus infection:
<3 months of age, <35 weeks gestation: 40 mg/kg/day IV 12 hourly for 14-21 days.
Give for 21 days in case of dissemination or encephalitis.
<3 months of age, >35 weeks gestation: 60 mg/kg/day IV 8 hourly for 14-21 days.
Herpes simplex virus Encephalitis:
3 months to 12 years: 20 mg/kg IV every 8 hours for 14 to 21 days.
>12 years: 10 mg/kg IV every 8 hours for 14 to 21 days.
Mucocutaneous Herpes Simplex Virus Infection: (in immunocompromised patients)
Children 2-12 years: 75 mg/kg/day PO in 5 divided doses for 5-7 days. Max: 1000 mg/day.
>12 years: 1000 mg/day in 5 divided doses for 7 to 10 days.
Suppression, chronic (cutaneous, ocular) episodes:
2-12 years: Oral: 30 mg/kg/day in 3 divided doses daily; Maximum dose: 1000 mg/day. Reassess after 12 months.
>12 years: 400 mg twice daily; reassess at 12 months.
HSV Prophylaxis for immunocompromised patients:
>2 years: 600-1000 mg/day divided into 3-5 doses/day PO.
Varicella Zoster (chickenpox):
Immunocompromised: IV
Infants: 10 mg/kg/dose every 8 hours for 7 to 10 days.
>1 year: 500 mg/m²/dose every 8 hours for 7 to 10 days; some experts recommend
10 mg/kg/dose every 8 hours.
Immunocompetent:
Children ≥2 years and Adolescents: 20 mg/kg/dose PO 4 times daily for 5 days; maximum daily dose: 3,200 mg/day. IV dose: 500 mg/m²/dose every 8 hours for 7 to 10 days; some experts recommend 10 mg/kg/dose every 8 hours.
Herpes zoster (shingles), prophylaxis:
Infants, Children, and Adolescents <40 kg: Oral: 60 to 80 mg/kg/day in 2 to 3 divided doses.
Children and Adolescents ≥40 kg: Oral: 800 mg twice daily.
Immunocompromised:
Infants, Children, and Adolescents: Oral: 20 mg/kg/dose 4 times daily for 7 days; maximum dose: 800 mg/dose.
Adverse Effect :
Contraindicated in patients hypersensitive to acyclovir. In high doses, polyuric renal failure has occurred therefore adequate hydration should be maintained to prevent dehydration.
Nausea, vomiting, diarrhea, reversible neurological dysfunction, inflammation at site of injection, elevated liver function tests, rash/hives and headache.
Renal Dose :
Dose in Renal Impairment GFR (mL/min)
| 25-50 | 5–10 mg/kg every 12 hours |
| 10-25 | 5–10 mg/kg every 24 hours (some units use 3.5–7 mg/kg every 24 hours) |
| <10 | 2.5–5 mg/kg every 24 hours |
Dose in Patients undergoing Renal Replacement Therapies
| CAPD | Not dialysed. Dose as in GFR<10 mL/min |
| HD | Dialysed. Dose as in GFR<10 mL/min |
| HDF/High flux | Dialysed. Dose as in GFR<10 mL/min |
| CAV/VVHD | Dialysed. Dose as in GFR=10–25 mL/min |
Hepatic Dose :
No dosage adjustments are recommended.