Acyclovir (Oral)

Indications
Aciclovir is indicated for-

The treatment of viral infections due to herpes simplex virus (type I & II) and varicella zoster virus (herpes zoster & chickenpox).
The treatment of herpes simplex virus infections of the skin and mucous membranes including initial and recurrent genital herpes.
The prophylaxis of herpes simplex infections in immunocompromised patients.

Therapeutic Class
Herpes simplex & Varicella-zoster virus infections

Pharmacology
Aciclovir is a synthetic purine derivative. Aciclovir exerts its antiviral effect on herpes simplex virus (HSV) and varicella-zoster virus by interfering with DNA synthesis and inhibiting viral replication. In cells infected with herpes virus, the antiviral activity of Aciclovir appears to depend principally on the intracellular conversion of the drug to Aciclovir Triphosphate. Aciclovir is converted to Aciclovir Monophosphate principally via virus coded thymidine kinase the monophosphate is phosphorylated to the diphosphate via cellular guanylate kinase and then via other cellular enzyme to the triphosphate which is the pharmacologically active form of the drug. 15-30% of an oral dose of the drug is absorbed from GI tract. Peak plasma concentrations usually occur within 1.5-2 hours after oral administration. It is widely distributed into body tissues and fluids including the brain, saliva, lung, liver, muscle, spleen, uterus, vaginal mucosa and secretions, CSF, and herpetic vesicular fluid. Aciclovir is excreted through the kidney by the glomerular filtration & tubular secretion.

Dosage & Administration
Treatment of initial herpes simplex:

Adult: 200 mg 5 times daily usually for 5 days. For immunocompromised patients 400 mg 5 times daily for 5 days or as directed by the registered physician.
Children under 2 years: half of the adults dose.
Children over 2 years: Adult dose.

Prophylactic treatment of herpes simplex in the immunocompromised:

Adult: 200 to 400 mg 4 times daily.
Children under 2 years: Half of the adult dose.
Children over 2 years: Adult dose.

Treatment of vericella (chicken pox):

Adult and children over 40 kg: 800 mg 4 times daily for 5 days.
Children 2 years of age and older (below 40 kg): 20 mg/kg per dose orally 4 times daily (80 mg/kg/day) for 5 days.

Treatment of herpes zoster (Shingles): 800 mg 5 times daily for 7 days.

For the treatment of initial rectal (Proctitis) herpes infections: 400 mg 5 times daily for 10 days or until clinical resolution occurs has been recommended.

Treatment of herpes simplex and prevention of recurrence: 200 mg 4 times daily or 400 mg twice daily possibly reduced to 200 mg 2 or 3 times daily and interrupted every 6-12 months.

Interaction
Concomitant administration of probenecid and acyclovir has reportedly increased the mean plasma half-life and decreased urinary excretion and renal clearance of acyclovir. Amphotericin B has been shown to potentiate the antiviral effect of acyclovir against pseudorabies virus in vitro when both drugs are added to the culture medium. Ketoconazole and acyclovir have shown dose-dependent, synergistic, antiviral activity against herpes simplex virus types 1 and 2 (HSV-1 and HSV-2) in in-vitro replication studies.

Contraindications
Aciclovir tablet is contraindicated in patients known to be hypersensitive to Aciclovir.

Side Effects
Rashes, gastro-intestinal disturbances, rises in bilirubin and liver-related enzymes, increases in blood urea and creatinine, decreases in hematological indices, headache, neurological reactions, fatigue.

Pregnancy & Lactation
Pregnancy category B. There is no adequate and well controlled studies in pregnant women. Aciclovir should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus. Caution should be exercised when it is administered to a nursing mother.

Precautions & Warnings
Aciclovir should be administered with caution to patient with renal impairment and doses should be adjusted according to creatinine clearance.

Storage Conditions
Acyclovir should be stored below 25°C. Protect from light and moisture. Keep drugs out of the reach of children.