4.1. Therapeutic indications

For the treatment of herpes simplex virus infections of the lips and face (herpes labialis).

Immunocompromised Patients

Aciclovir cream is not recommended for use in immunocompromised patients. Such patients must be advised to consult a physician concerning the treatement of any infection.

4.2. Posology and method of administration

Route of administration - Topical

Adults and children

Treatment should be initiated as soon as possible after the start of the infection, ideally during the prodromal period or when the lesions first appear. Treatment can also be started during the later (papule or blister) stages.

A thin film of cream should be applied to the infected and immediately adjacent skin areas 5 times daily at 4-hour intervals during the day omitting the night time application.

Treatment should be continued for 4 days, If healing has not occurred, treatment may be continued for up to 10 days. If lesions are still present after 10 days, users should be advised to consult a doctor.

Patients should wash their hands before and after applying the cream and avoid unnecessary rubbing of the lesions or touching with a towel, to avoid aggravating or transferring the infection.

Elderly

No special requirements

4.3. Contraindications

Hypersensitivity to aciclovir, valaciclovir, propylene glycol to any of the excipients listed in section 6.1.

4.4. Special warnings and precautions for use

Only recommended for use on cold sores on the lips and face.

People with particularly severe recurrent herpes labialis should be encouraged to seek medical advice.

Not to be applied to mucous membranes such as inside the mouth or vagina, or on the eye. Particular care should be taken to avoid contact with the eye.

Not for use for the treatment of genital herpes or ocular herpes infections.

Not recommended for use by patients who know they are immunocompromised e.g. by HIV infection, bone marrow transplant or cancer treatment, except on the advice of a doctor. Such individuals should be encouraged to consult a physician concerning the treatment of an infection.

Cold sore sufferers should be advised to avoid transmitting the virus, particularly when active lesions are present.

The excipient propylene glycol can cause skin irritations and the excipient cetyl alcohol can cause local skin reactions (e.g. contact dermatitis)

4.5. Interaction with other medicinal products and other forms of interaction

Probenecid increases the mean half-life and area under the plasma concentration curve of systemically administered aciclovir. Other drugs affecting renal physiology could potentially influence the pharmacokinetics of aciclovir. However this is likely to be of little relevance to the cutaneous application of aciclovir.

No interactions with other drugs have been described for topical Acyclovir.

4.6. Fertility, pregnancy and lactation

Pregnancy

No specific studies of topical aciclovir have been carried out in pregnant women or nursing mothers.

So far, no relevant plasma levels have been measured and no systemic effects have been observed.

A post-marketing aciclovir pregnancy registry has documented pregnancy outcomes in women exposed to any formulation of aciclovir. The birth defects described amongst aciclovir exposed subjects have not shown any uniqueness or consistent pattern to suggest a common cause.

In internationally accepted standard tests the systemic administration of Aciclovir 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.

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

Use of the cream should be considered only when the potential benefit outweighs the possibility of unknown risks however the systemic exposure to aciclovir from topical application of aciclovir cream is very low.

Fertility

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

There is no experience of the effect of aciclovir tablets on human female fertility. Aciclovir tablets have been shown to have no definite effect upon sperm count, morphology or motility in man. See Clinical Studies in section 5.2.

Lactation

Following oral administration of 200 mg aciclovir five times a day, aciclovir has been detected in breast milk at concentrations ranging from 0.6 to 4.1 times the corresponding plasma levels. These levels would potentially expose breast fed infants to aciclovir doses of up to 0.3 mg/kg/day. The dosage received by a nursing infant following maternal use of aciclovir cream would be expected to be insignificant.

4.7. Effects on ability to drive and use machines

The medicinal product has no influence on the ability to drive or operate machinery.

4.8. Undesirable effects

The following convention has been used for the classification of undesirable effects in terms of frequency:-

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.

Skin and subcutaneous tissue disorders

Uncommon

- Itching

- Transient burning or stinging following application of aciclovir cream

- Mild drying or flaking of the skin

Rare

- Erythema

- Contact dermatitis following application. Where sensitivity tests have been conducted, the reactive substances have most often been shown to be components of the cream base rather than aciclovir.

Immune system disorders

Very rare

- Immediate hypersensitivity reactions including angioedema and urticaria.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the Yellow Card Scheme at www.mhra.gov.uk/yellowcard.

4.9. Overdose

Overdose is unlikely to occur, if the cream is applied locally and as indicated. There are no reports concerning an overdose of aciclovir cream.

No unwanted effects would be expected if the entire contents of a 2.0g tube of the cream were ingested. Doses of 800 mg five times daily (4 g per day), have administered without adverse effects. Single intravenous doses of up to 80 mg/kg have been inadvertently administered without adverse effects. Aciclovir is dialysable.