Adults and children two years and above: 200 mg five times daily at approximately four-hourly intervals omitting the night time dose. Treatment should continue for five days but in severe infections, treatment may have to be extended.

Children below two years: Half the adult dose.

In severely immunocompromised patients (e.g. after marrow transplant)
or in patients with impaired absorption from the gut, the dose can be doubled to 400 mg or, alternatively, intravenous dosing could be considered.

Dosing should begin as early as possible after the start of an infection. For recurrent episodes this should preferably be during the prodromal period or when lesions first appear.

Suppression of Herpes Simplex
In immunocompetent patients, 200 mg should be taken four times daily at approximately six-hourly intervals. Many patients may be conveniently managed on a regimen of 400 mg taken twice daily at approximately twelve-hourly intervals. Some patients may experience break-through infections on total doses of 800 mg. Therapy should be interrupted periodically at intervals of six to twelve months in order to observe possible changes in the natural history of the disease. No specific data are available on the suppression of herpes simplex infections in immunocompetent children.

Prophylaxis of Herpes Simplex Infections
Adults and children two years and above: In immunocompromised patients, 200 mg should be taken four times daily at approximately six-hourly intervals. In severely immunocompromised patients (e.g. after marrow transplant) or in patients with impaired absorption from the gut the dose can be doubled to 400 mg or, alternatively, intravenous dosing could be considered.

Children below two years: Half the adult dose.

The duration of prophylactic administration is determined by the duration of the period at risk.

Treatment of Varicella Infections
Adults: 800 mg five times daily at approximately four-hourly intervals, omitting the night time dose. Treatment should continue for seven days.

Children (two-six years): 400 mg four times daily for five days.

Children below two years: 200 mg four times daily for five days.
Dosing may be more accurately calculated as 20 mg/kg body weight (not to exceed 800 mg) four times daily.

Treatment of Herpes Zoster Infections
Adults: 800 mg five times daily at approximately four-hourly intervals omitting the night time dose. Treatment should continue for seven days.

Children: No specific data are available on the treatment of herpes zoster infections in immunocompetent children. Limited data suggest that for management of severely immunocompromised children, over two years of age, the adult dose may be given.

Dosing should begin as early as possible after the start of an infection; treatment yields better results if initiated as soon as possible after onset of the rash.

In the elderly: In the elderly, total acyclovir body clearance declines in parallel with creatinine clearance. Adequate hydration of elderly patients taking high oral doses of acyclovir should be maintained. Special attention should be given to dosage reduction in elderly patients with impaired renal function.

In renal impairment: For patients on treatment and prophylaxis of herpes simplex with severe renal impairment (creatinine clearance less than 10 ml/minute) an adjustment of dosage to 200 mg twice daily at approximately twelve-hourly intervals is recommended.

In the treatment of Varicella and Herpes zoster infections and in the management of severely immunocompromised patients it is recommended to adjust the dosage to 800 mg twice daily, at approximately twelve-hourly intervals, for patients with severe renal impairment (creatinine clearance less than 10 ml/minute) and to 800 mg three times for patients with moderate renal impairment (creatinine clearance in the range 10 to 25 ml/minutes).

2. THERAPEUTIC / DIAGNOSTIC CLAIMS

Health 2000 Aciclovir 400 mg tablet is indicated for the treatment of Herpes simplex virus infections of the skin and mucous membrane, including initial and recurrent genital herpes, suppression of recurrent Herpes simplex infections in immunocompetent patients; prophylaxis of Herpes simplex infection in immunocompromised patients; varicella (chicken pox) and Herpes zoster (shingles) infections; and management of severely immunocompromised, namely those with HIV disease (CD4+ count < 200/cu.mm, including patients with AIDS or severe ARC) or after bone marrow transplantation.

3. DESCRIPTION OF DOSAGE FORM

Aciclovir is a synthetic purine nucleoside analogue with in vitro and in vivo inhibitory activity against human herpes viruses including herpes simplex virus (HSV) type 1 and 2, Varicella zoster virus (VZV), Epstein-Barr virus.

4. CONTRAINDICATIONS

Hypersensitivity to acyclovir or intolerance to components of the formulation.

WARNINGS AND PRECAUTIONS

DRUG INTERACTIONS
Probenecid increases the acyclovir mean half-life and area under the plasma concentration-time curve. Other drugs affecting renal physiology could potentially influence the pharmacokinetics of acyclovir. However, clinical experience has not identified other drug interactions with acyclovir.

USE DURING PREGNANCY AND LACTATION
No adequate data is available regarding the effect of acyclovir during human pregnancy. Hence caution should be exercised while prescribing acyclovir during pregnancy. Following 200 mg five times daily, acyclovir has been detected in breast milk at concentration 0.6 to 4.1 times the plasma levels. Caution is therefore advised if acyclovir is to be administered to a nursing woman.

OTHERS
The recommended dosage should not be exceeded. All patients should be advised to take particular care to avoid potential transmission of virus if active lesions are present while they are on therapy. Caution should be exercised when administering to patients receiving potentially nephrotoxic agents.

5. SIDE EFFECTS

Skin rashes have been reported in a few patients; the rashes have resolved on withdrawal of the drug.

Gastrointestinal effects, including nausea, vomiting, diarrhea and abdominal pain have been reported in some patients.

Reversible neurological reactions, notably dizziness, confusional states, hallucinations and somnolence have occasionally been reported, usually in patients with renal impairment or other predisposing factors.

Other events reported rarely in patients receiving oral formulations of acyclovir include mild, transient rises in bilirubin and liver-related enzymes, small increases in blood urea and creatinine, small decreases in haematological indices, headaches and fatigue.

In patients receiving anti-retroviral therapy no significant increase in toxicity was associated with the addition of acyclovir.

6. TOXIC EFFECTS

MUTAGENICITY, CARCINOGENECITY AND TERATOGENECITY
There is no evidence of carcinogenicity after administration of single daily doses of up to 450 mg.kg-1 by gavage to rats and mice for a lifetime.

Acyclovir showed no evidence of teratogenicity in standard tests of daily dosing in rats (50 mg.kg-1 subcutaneously), mice (450 mg.kg-1 orally), and rabbits (50 mg.kg-1 by the subcutaneous and intravenous routes).

Aciclovir was tested in 16 genetic toxicity assays. No evidence of mutagenicity was observed in four microbial assays. Aciclovir demonstrated mutagenic activity in two in vitro cytogenetic assays (one mouse lymphoma cell line and human lymphocytes). No mutagenic activity was observed in five in vitro cytogenetic assays (three Chinese hamster ovary cell lines and two mouse lymphoma cell lines). A positive result was demonstrated in one of two in vitro cell transformation assays, and morphologically transformed cells obtained in this assay formed tumors when inoculated into immunosuppressed, syngeneic, weanling mice. No mutagenic activity was demonstrated in another, possibly less sensitive, in vitro cell transformation assay.

CONTACT INFORMATION

Tel: (905) 264 2641 / (905) 882-7036
Fax: (905) 264 2825 / (905) 882-7063

General Inquiries info@health-2000.com
Director of Sales dsales@health-2000.com
Director of Marketing dmarketing@health-2000.com
Product Information products@health-2000.com
Custom Manufacturing cmanufacturing@health-2000.com

Health 2000 Inc.
70 East Beaver Creek Road
Richmond Hill, Ont.
Canada, L4B 3B2