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ACYCLOVIR

PHARMACOLOGICAL ACTION
Acyclovir is phosphorylated after entering the herpes infected cells to the active acyclovir triphosphate compound. It is active in vitro against type I and II herpes simplex and varicella zoster viruses.
The HSV coded thymidine kinase must be present before phosphorilation can take place. The Acyclovir triphosphate prevents synthesis by inhibiting herpes specified DNA polymerase. This process takes place without affecting the normal cellular processes.

INDICATIONS
Herpes simplex infections of the skin and mucous membranes including genital herpes (initial and recurrent) if given as soon as possible after symptoms appear.
Suppression of recurrent herpes simplex infections in patients with a incompetent immune system. Indicated for shingles if the lesion is not older than 72 hours.
If used within 24 hours after appearance of typical chickenpox rash, acyclovir is indicated for treatment of the Varicella Zoster or chickenpox virus.
In HIV positive patients, who are severely immuno-compromised, acyclovir is indicated to reduce the risk of developing herpes infections. Acyclovir could be used in combination with zidovudine in patients with advanced HIV disease.

CONTRA-INDICATIONS
Any known hypersensitivity to acyclovir.
Pregnancy and lactation: Safety has not been established.

DOSAGE AND DIRECTIONS FOR USE
INDICATION DOSAGE COMMENTS
Initial and recurrent herpes simplex infections of skin and mucous membranes. 200 mg 5 times daily at 4 hourly intervals for 5 days In severe initial infection, extend treatment. In immuno-compromised patients, dosage could be increased to 400 mg. The first dose should be administered as early as possible after start of infection.
Suppression of recurrent genital herpes simplex infections in immuno-compromised patients 200 mg acyclovir 4 times daily at 6 hourly intervals, or 400 mg 12 hourly. Some patients may have breakthrough infections on 800 mg daily.
Interrupt therapy every 6-12 months to observe history of disease.
Prophylaxis of herpes simplex infections in immuno-compromised patients. 200 mg 4 times daily at 6 hourly intervals In severely immuno-compromised patients, or impaired absorption from the gut, dosage could be doubled to 400 mg.
Treatment of varicella zoster in adolescents (12-18) years 800 mg 4 times a day for 5 days. 
Treatment of varicella zoster in herpes infections in adults. 800 mg 5 times daily at 4 hourly intervals for 7 days. Start treatment as early as possible. In severely immuno-compromised patients, or patients with impaired gut absorption, IV dosing should be considered.
Management of severely immuno-compromised patients 800 mg 4 times daily at 6 hourly intervals. 
Dosage in children:
Herpes simplex and prophylaxis of herpes simplex infections in immuno-compromised patients 2 years and older.
Adult dose. Orally administered acyclovir in children less than 2 years in age has not yet been fully studied.
treatment of varicella zoster (chickenpox) in children 20 mg acyclovir per kg bodymass 4 times daily for 5 days. Dosage may not exceed 800 mg daily and start treatment as soon as chickenpox rash appear.
Dosage in elderly:   Adequate hydration in patients taking high doses must be maintained. Acyclovir clearance in body declines parallel with creatinine clearance.
Treatment of prophylaxis of herpes simplex infections in patients with renal impairment. 200 mg every 12 hours if creatinine clearance <10 mL/minute. 
Treatment of varicella zoster, herpes zoster and immuno-compromised patients with renal impairment. 800 mg twice daily at 12 hourly intervals (creatinine clearance <10 mL/minute).
800 mg 3 times daily with 8 hourly intervals (creatinine clearance <10-25 mL/minute)
 

SIDE-EFFECTS
Effects on skin: Skin rashes which disappear after withdrawal of medication.
Effects on gastro-intestinal tract: Nausea, vomiting, diarrhoea and vomiting.
Other reactions: Reversible neurological reactions, dizziness, hallucinations and somnolence especially in patients with renal impairment. Rises in bilirubin and liver related enzymes, elevations in blood and and creatinine; minimal decreases in haematological indices, headaches and fatigue. Accelerated diffuse hair loss has also been reported.
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