ACICLOVIR 5% W/W CREAM - summary of medicine characteristics

1 NAME OF THE MEDICINAL PRODUCT

Aciclovir 5%w/w Cream

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

1g of cream contains 50mg aciclovir

For excipients see 6.1

3 PHARMACEUTICAL FORM

Cream.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

The treatment of herpes simplex virus infections of the of the lips and face (recurrent 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 treatment of any infection.

4.2 Posology and method of administrationRoute of administration - topical

Adults and children: 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.

Aciclovir cream should be applied to the lesions or impending lesions as soon as possible, preferably during the early stages (prodrome or erythema).

Treatment can also be started during the later (papule or blister) stages.

Treatment should be continued for at least 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. Users should wash their hands before and after applying the cream, and avoid unnecessary rubbing of the lesions or touching them with a towel, to avoid aggravating or transferring the infection.

Use in the elderly: No special comment

4.3 Contraindications

Hypersensitivity to aciclovir, valaciclovir, propylene glycol or any other ingredients of the preparation.

4.4 Special warnings and precautions for use

Aciclovir cream should only be used on cold sores on the mouth and face. It is not recommended for application to mucous membranes, such as in the mouth or eye and must not be used to treat genital herpes.

Particular care should be taken to avoid contact with eye. People with particularly severe recurrent herpes labialis should be encouraged to seek medical advice.

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

Aciclovir cream is not recommended or use by people who know that they are immunocompromised. Such individuals should be encouraged to consult a physician concerning the treatment of any infection.

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

Ocular herpes

Aciclovir Cream must not be used for treatment of ocular herpes infections.

Genital herpes

Aciclovir Cream must not be used for treatment of genital herpes.

4.5 Interaction with other medicinal products and other forms of interaction

No clinically significant interactions have been identified.

4.6 Fertility, pregnancy and lactation

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

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

The use of Lip Sore Cream should be considered only when the potential benefits outweigh the possibility of unknown risks however the systemic exposure to aciclovir from topical application of aciclovir cream is very low.

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 Lip Sore Cream would be expected to be insignificant.

There is no information on the effect of aciclovir on human female fertility.

See Clinical Studies in section 5.2

4.7 Effects on ability to drive and use machines None known.

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

Transient burning or stinging following application of aciclovir Cream

Itching

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

No untoward effects would be expected if the entire 2g contents of Lip Sore Cream containing 100mg of aciclovir were ingested orally or applied topically.

5.1 Pharmacodynamic properties

ATC Code: D06 BB 03

Aciclovir is an antiviral agent which is highly active in vitro against herpes simplex virus (HSV) types 1 and 2. Toxicity to mammalian host cells is low.

Aciclovir is phosphorylated after entry into herpes infected cells to the active compound aciclovir triphosphate. The first step in this process is dependent on 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.

In two multicentre, double blind, randomised clinical studies involving 1,385 subjects treated over 4 days for recurrent herpes labialis, Aciclovir Cream 5% was compared to vehicle cream. Based on the pooled dataset from the two studies the mean time from clinician-assessed start of treatment to healing (episode duration) was 4.6 days using Aciclovir Cream and 5.0 days using vehicle cream (p<0.001). The median clinician-assessed episode duration was 4.0 days using aciclovir cream (25%-ile=3.0 days, 75%-ile=6.0 days) and 4.3 days using vehicle cream (25%-ile=3.1 days, 75%-ile=6.6 days), with a corresponding hazard ratio of 1.22 (p<0.001).

The median duration of subject-assessed pain was 2.9 days using aciclovir cream and 3.0 days using vehicle cream, with a corresponding hazard ratio of 1.21 (p<0.001).

Overall, approximately 60% of subjects started treatment at an early lesion stage (prodrome or erythema) and 40% at a late stage (papule or vesicle).

5.2 Pharmacokinetic properties

Pharmacology studies have shown only minimal systemic absorption of aciclovir following repeated topical administration of Lip Sore Cream.

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.

5.3 Preclinical safety data

6   PHARMACEUTICAL PARTICULARS

6.1 List of excipients

Stearoyl macrogolgycerides

Dimeticone

Cetyl alcohol

Liquid paraffin

White soft paraffin

Propylene glycol

Purified water

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

3 years

6.4 Special precautions for storage

Do not store above 25°C. Do not refrigerate or freeze.

6.5 Nature and contents of container

The cream is filled into tubes. The tubes consisting of aluminium are closed with a polypropylene cap. The tubes are packed into cardboard boxes together with package leaflets.

Pack sizes: Tubes of 2g, 10g.

6.6 Instructions for use and handling (and disposal)

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

Relonchem Limited Cheshire House Gorsey Lane Widnes Cheshire

WA8 0RP

United Kingdom

8 MARKETING AUTHORISATION NUMBER(S)

PL 20395/0002

9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

17th May 2005