GlaxoSmithKline (Ireland) Ltd

Zovirax 30 mg/g Eye Ointment

Each gram of ointment contains 30 mg aciclovir equivalent to 3% w/w aciclovir.

For a full list of excipeints, see 6.1.

Eye Ointment.

A soft, homogenous, white to off-white, slightly translucent, unctuous mass.

In the treatment of Herpes simplex keratitis.

For ophthalmic administration.

Adults and children: A l cm ribbon of the ointment should be placed inside the lower conjunctival sac five times a day at approximately four-hourly intervals. Treatment should continue for at least 3 days after healing is complete.

Zovirax Ophthalmic Ointment is contra-indicated in patients known to be hypersensitive to aciclovir or valaciclovir.

Patients should be informed that transient mild stinging immediately following application may occur.

Patients should avoid wearing contact lenses when using Zovirax Ophthalmic Ointment.

No clinically significant interactions have been identified.

A post-marketing aciclovir pregnancy registry has documented pregnancy outcomes in women exposed to any formulation of Zovirax. The registry findings have not shown an increase in the number of birth defects amongst Zovirax exposed subjects compared with the general population, and any birth defects showed no uniqueness or consistent pattern to suggest a common cause.

Experience in humans is limited, so the use of Zovirax Eye Ointment should be considered only when the potential benefits outweigh the possibility of unknown risks.

Systemic administration of aciclovir in internationally accepted standard tests did not produce embryotoxic or teratogenic effects in rabbits, rats or mice.

In a non-standard test in rats, foetal abnormalities were observed but only following such high subcutaneous doses that maternal toxicity was produced. The clinical relevance of these findings is uncertain.

Limited human data show that the drug does pass into breast milk following systemic administration. However, the dosage received by a nursing infant following maternal use of Zovirax Ophthalmic Ointment would be insignificant.

No specific studies have been conducted, but there is no evidence to suggest that aciclovir will adversely affect ability to drive and operate machines.

Adverse reactions are listed below by MedDRA body system organ class and by frequency.

The frequency categories used are: very common 1/10, common 1/100 and <1/10, uncommon 1/1000 and <1/100, rare 1/10,000 and <1/1000 very rare <1/10,000.

Clinical trial data have been used to assign frequency categories to adverse reactions observed during clinical trials with aciclovir 3% ophthalmic ointment. Due to the nature of the adverse events observed, it is not possible to determine unequivocally which events were related to the administration of the drug and which were related to the disease. Spontaneous reporting data has been used as a basis for allocating frequency for those events observed post-marketing.

Immune system disorders

Very rare: Immediate hypersensitivity reactions including angioedema

Eye Disorders

Very common: Superficial punctate keratopathy

This did not necessitate an early termination of therapy and healed without apparent sequelae.

Common: Transient mild stinging of the eye occurring immediately following application, conjunctivitis

Rare: Blepharitis

Local irritation and inflammation such as blepharitis and conjunctivitis have been reported in patients receiving Zovirax Ophthalmic Ointment.

No untoward effects would be expected if the entire content of the tube containing 135mg of aciclovir were ingested orally.

Aciclovir is an antiviral agent which is highly active in vitro against Herpes simplex (HSV), types I and II and varicella zoster viruses.

Aciclovir is phosphorylated to the active compound aciclovir triphosphate after entry into a Herpes infected cell. The first step in this process requires the presence of the HSV coded thymidine kinase. Aciclovir triphosphate acts as an inhibitor of and substrate for the herpes specified DNA polymerase preventing further viral DNA synthesis without affecting normal cellular processes.

Aciclovir is rapidly absorbed from the eye ointment through the corneal epithelium and superficial ocular tissues with the result that viraltoxic concentrations are achieved in the aqueous humor. It has not been possible to detect aciclovir in the blood by existing methods after topical application to the eye. However, trace quantities may be measured in the urine. These levels are not clinically significant.

There is no information on the effect of aciclovir oral formulations or i.v. for infusion on human female fertility. In a study of 20 male patients with normal sperm count, oral aciclovir administered at doses of up to 1g per day for up to six months has been shown to have no clinically significant effect on sperm count, motility or morphology.

NON-CLINICAL INFORMATION

Mutagenicity

The results of a wide range of mutagenicity tests in vitro and in vivo indicate that aciclovir is unlikely to pose a genetic risk to man.

Carcinogenicity

Aciclovir was not found to be carcinogenic in long-term studies in the rat and the mouse.

Fertility

Largely reversible adverse effects on spermatogenesis in association with overall toxicity in rats and dogs have been reported only at doses of aciclovir greatly in excess of those employed therapeutically. Two-generation studies in mice did not reveal any effect of (orally administered) aciclovir on fertility.

White Petrolatum

Not applicable

2 years .

Do not store above 25°C.

Discard one month after opening.

White to pale yellow sterile ointment contained in pure tin or lacquered aluminium tubes with a tamper evident screw cap.

Pack sizes: 4.5g tube.

No special requirements.

GlaxoSmithKline (Ireland) Limited.,

Stonemasons Way,

Rathfarnham,

Dublin 16.

PA 1077/84/2

26^th August 1981 / 26^th August 2006

April 2007