INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION
VYROHEXAL

SCHEDULING STATUS:
S4

PROPRIETARY NAME
(and dosage form):

VYROHEXAL

VyroHexal 200 (tablets)
VyroHexal 400 (tablets)

COMPOSITION
Each VyroHexal 200 tablet contains 200 mg acyclovir.
Each VyroHexal 400 tablet contains 400 mg acyclovir.

PHARMACOLOGICAL CLASSIFICATION
A 20.2.8. Antiviral agents

PHARMACOLOGICAL ACTION
Acyclovir is active in vitro against Herpes simplex type I and type II and Varicella Zoster virus. Once inside the herpes infected cells acyclovir is phosphorylated to the active compound acyclovir triphosphate. Acyclovir triphosphate acts as an inhibitor of and substrate for the herpes specified DNA polymerase, preventing further viral DNA synthesis, without affecting normal cellular processes.

INDICATIONS
Treatment of initial and recurrent Herpes simplex infections of the skin and mucous membranes, including initial and recurrent genital herpes simplex virus infections.
Prophylaxis of Herpes simplex infections in immunocompromised patients.
Treatment of Herpes zoster (shingles) infections if the lesions are not older than 72 hours.
Treatment of Varicella zoster (chickenpox), within 24 hours of the appearance of the typical chickenpox rash.
Reduction of mortality and risk of developing Herpes virus infections in certain severely immunocompromised patients i.e. those with advanced HIV disease (CD4+ counts <200/m³ including patients with AIDS and ARC) or following bone marrow transplantation. In advanced HIV disease, oral acyclovir has been used in conjunction with oral zidovudine.
In patients following bone-marrow transplantation oral acyclovir must be preceded by one month’s intravenous treatment with acyclovir.

CONTRA-INDICATIONS
Hypersensitivity to acyclovir.
Safety in pregnancy and lactation has not been established.

DOSAGE AND DIRECTIONS FOR USE
Adults
Treatment of recurrent Herpes simplex infection of skin and mucous membranes : 200 mg five times per day every 4 hours omitting the night time dose. Treatment should continue for 5 days but in case of severe initial infection, this period may have to be extended.
In patients that are severely immunocompromised or in patients with decreased gut absorption the dose may be doubled to 400 mg or alternatively, intravenous acyclovir should be considered.
Dosing should be started as early as possible following the start of infection and for recurrent episodes this should be in the prodromal stages or when lesions first appear.
Suppression of recurrent genital Herpes simplex infections in immuno-competent adults : 200 mg four times per day at six hourly intervals. Patients may be conveniently managed at a dose of 400 mg twice daily at 12 hourly intervals. This dose may be titrated down to 200 mg acyclovir eight to twelve hourly.
Therapy should be interrupted, every 6 to 12 months, to observe possible changes in the natural history of the disease.
Prophylaxis of Herpes simplex infections in immunocompromised adults
200 mg four times daily at six hourly intervals.
In patients that are severely immunocompromised or in patients with decreased gut absorption the dose may be doubled to 400 mg or alternatively intravenous acyclovir should be considered.
The duration of prophylactic administration is determined by the duration of the period at risk.
For treatment of Herpes zoster infections in adolescents (12 to 18 years)
800 mg four times daily for five days.
For treatment of Varicella zoster and Herpes zoster infections in adults
800 mg 5 times daily at four hourly intervals, omitting the night time dose for a minimum period of seven days. Dosing should be initiated as early as possible after the start of an infection.
Dosage for management of severely immunocompromised patient
800 mg four times daily, every six hours.
In the management of bone marrow recipients this would be preceded by up to one month’s therapy with intravenous acyclovir 500 mg/m² three times daily. The duration of treatment studied in bone marrow transplant patients was 6 months (from 1 to 7 months post-transplant). In patients with advanced HIV disease, study treatment was 12 months.

Dosage in children
Treatment and prophylaxis of Herpes simplex infections in immunocompromised children
Two years and older : Adult dosage.
Below 2 years : Half the adult dosage.
Oral administration of acyclovir in patients less than 2 years of age has not been fully studied.
Dosing for Varicella (chickenpox) may be calculated as 20 mg acyclovir per kg body mass (not exceeding 800 mg) four times daily.
Treatment should be initiated within 24 hours after appearance of typical chickenpox rash, and should continue for five days.
Limited data suggests that for severely immunocompromised children over 2 years, the adult dosage can be administered.

Elderly
Total acyclovir body clearance declines with creatinine clearance. Adequate hydration of elderly patients receiving high oral acyclovir should be maintained. Dosage reduction is recommended in elderly patients with renal impairment.

Dosage in renal impairment
Treatment and prophylaxis of Herpes simplex infection in patients with impaired renal function : the recommended oral dose will not lead to accumulation of aciclovir.
A dose of 200 mg every twelve hours is recommended in patients with severe renal impairment (creatinine clearance less than 10 mL / minute).
Treatment of Varicella and Herpes Zoster infections :
Severe renal impairment ( creatinine clearance less than 10 mL/min) : adjust dosage to 800 mg twice daily at 12 hourly intervals.
Moderate renal impairment (creatinine clearance ranging between 10 - 25 mL/min : adjust dose to 800 mg three times daily every eight hours

Normal dosage (5 times daily)	Creatinine clearance (mL/min/1,73m2 )	Adjusted dosage
		Dose ( mg)	Dosing interval (Hours)
200 mg every 4 hours	>10	200	Every 4 hours 5 times daily
	0 - 10	200	Every 12 hours
800 mg every 4 hours	10 - 25	800	Every eight hours
	0 - 10	800	Every 12 hours

SIDE-EFFECTS AND SPECIAL PRECAUTIONS
Skin rashes have occurred however these have resolved following withdrawal of the oral formulation. Gastro-intestinal effects, including nausea, vomiting, diarrhoea and abdominal cramps have been reported.
Reversible neurological reactions including dizziness, confusional states, hallucinations and somnolence have been reported, usually in patients with renal impairment or other predisposing factors.
Reports of accelerated diffuse hair loss have been receivedbut the relationship between this phenomena and acyclovir therapy is unclear.
The following have also been reported : transient rises in bilirubin and liver related enzymes , increases in blood urea and creatinine, small decreases in blood indices, headaches, reversible neurological reactions, fatigue, fever, haematological changes, agitation, tremors, seizures, and coma have been reported, particularly in those who are immunocompromised.
Precautions
Acyclovir should be administered with caution to patients with renal impairment and doses should be adjusted according to creatinine clearance (see Dosage and Directions for use)
Interactions
Probenecid - concomitant administration leads to an increase in the plasma half life of aciclovir.
The risk of renal impairment is increased by the concomitant use of other nephrotoxic agents.

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT
See side effects and special precautions. No data are available on the effects of ingestion of high doses. Acyclovir is dialysable by haemodialysis. Treatment is supportive and symptomatic.

IDENTIFICATION
VyroHexal 200 mg tablets - White, round, biconvex tablets with a 120° cross breaking notch on one side and smooth surface. Diameter: 12.1 + 0.2 mm. Height: 4.5 + 0.4 mm
VyroHexal 400 mg tablets - White, round, biconvex tablets with a break notch on one side and smooth surface. diameter : 12,1 + 0,2 mm height : 5,5 + 0,4 mm

PRESENTATION
VyroHexal 200 mg tablets –transparent PVC / Aluminium blister packs containing 25 tablets
VyroHexal 400 mg tablets –transparent PVC / Aluminium blister packs containing 70 tablets

STORAGE INSTRUCTION
Protect from light.
Store below 25°C in a dry place.
KEEP OUT OF REACH OF CHILDREN

REGISTRATION NUMBERS
VyroHexal 200 - 32/20.2.8/0378
VyroHexal 400 - 32/20.2.8/0379

NAME AND BUSINESS OF ADDRESS OF APPLICANT
Hexal Pharma (SA) (PTY) Ltd
10 Fangio Road
Mahogany Ridge
Westmead
3610

DATE OF PUBLICATION OF THIS PACKAGE INSERT
30/10/2000        VYRAP1

New addition to this site: February 2002
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