SUMMARY OF PRODUCT CHARACTERISTICS

1 NAME OF THE MEDICINAL PRODUCT

Aciclovir 5% w/w Cream

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

Aciclovir 50 mg/g Excipients with known effect:

This product contains propylene glycol and cetyl alcohol.

For the full list of excipients, see 6.1

3    PHARMACEUTICAL FORM

Cream.

4    CLINICAL PARTICULARS

4.1    Therapeutic indications

Aciclovir Cream is indicated for the treatment of herpes simplex virus infections of the skin including initial and recurrent genital herpes and herpes labialis.

4.2 Posology and method of administration

Posology

Adults and children: Aciclovir Cream should be applied five times daily at approximately four hourly intervals, 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 for herpes labialis and for 5 days for genital herpes. If healing has not occurred then treatment may be continued for up to an additional 5 days.

Use in the elderly: No special comment

Method of administration

Cutaneous use

4.3 Contraindications

Aciclovir Cream is contraindicated in patients in case of hypersensitivity to aciclovir, valaciclovir, propylene glycol or any of the other excipients of the cream listed in section 6.1.

4.4    Special warnings and precautions for use

Aciclovir Cream is not recommended for application to mucous membranes such as in the mouth, eye or vagina as it may be irritant. Particular care should be taken to avoid accidental introduction into the eye.

Aciclovir Cream is for cutaneous use only and should not be swallowed.

In severely immunocompromised patients, (e.g. AIDS patients or bone marrow transplant recipients) oral dosing should be considered. These patients should be encouraged to consult a physician concerning the treatment of any infection.

The excipient propylene glycol can cause skin irritation 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

No clinically significant interactions have been identified.

4.6    Fertility, pregnancy and lactation

Pregnancy

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

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.

The use of aciclovir 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.

Teratogenicity

Effects in non-clinical studies were observed only at exposures considered sufficiently in excess of the maximum human exposure to indicate little relevance to clinical use (see section 5.3).

Breast-feeding

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 aciclovir cream would be insignificant.

Fertility

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

In a study of 20 male patients with normal sperm count, oral aciclovir administered at doses of up to 1 g per day for up to six months has been shown to have no clinically significant effect on sperm count, motility or morphology.

See Clinical Studies in section 5.2

4.7 Effects on ability to drive and use machines

Topically applied aciclovir does not affect the ability to drive or use machines.

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.

Immune system disorders

Very rare: Immediate hypersensitivity reactions including angioedema and urticaria. Skin and subcutaneous tissue disorders

Uncommon: Transient burning or stinging following application of aciclovir cream. Mild drying or flaking of the skin.

Itching.

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 rather than aciclovir.

Aciclovir Cream is usually well tolerated. Other undesirable effects that may occur after use of Aciclovir Cream are redness, tension, or pain of the skin at the site of the application.

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 contents of the tube containing 500 mg of aciclovir (cream) were ingested orally.

However the accidental, repeated overdose of oral aciclovir, over several days has resulted in gastrointestinal effects (nausea and vomiting) and neurological effects (headache and confusion). Aciclovir is dialysable by haemodialysis.

5    PHARMACOLOGICAL PROPERTIES

5.1    Pharmacodynamic properties

Pharmacotherapeutic group: chemotherapeutics for topical use ATC code: D06BB03

Aciclovir is an antiviral agent which is highly active in vitro against herpes simplex virus (HSV) types I and II and varicella zoster virus. 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 large, 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. In these studies, time from start of treatment to healing was 4.6 days using Aciclovir Cream and 5.0 days using vehicle cream (p<0.001). Duration of pain was 3.0 days after start of treatment in the Aciclovir Cream group and 3.4 days in the vehicle group (p=0.002). Overall, approximately 60% of patients started treatment at an early lesion stage (prodrome or erythema) and 40% at a late stage (papule or blister). The results were similar in both groups of patients.

5.2    Pharmacokinetic properties

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

5.3    Preclinical safety data

The results of a wide range of mutagenicity tests in vitro and in vivo indicate that aciclovir does not pose a genetic risk to man.

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

Largely reversible adverse effects on spermatogenesis in association with overall toxicity in rats and dogs have been reported only at systemic 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.

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.

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

6    PHARMACEUTICAL PARTICULARS

6.1    List of excipients

Purified water Propylene glycol Liquid paraffin White soft paraffin Cetyl alcohol Dimeticone Arlatone 983 S

6.2    Incompatibilities

Not applicable

6.3    Shelf life

3 years

The shelf-life after first opening is 4 weeks.

6.4    Special precautions for storage

Do not store above 30°C

6.5    Nature and contents of container

Aluminium tubes containing 2, 5, 10 or 20 g of cream. The tube is lacquered with epoxy-phenolic resin and closed by a HDPE cap. Single tubes are packed in a carton box.

6.6    Special precautions for disposal

Before and after application of the cream, it is advised to wash the hands thoroughly, to avoid contamination of other parts of the body. It may be advisable to use a finger cot or rubber glove. Close the tube carefully after usage.

Aciclovir Cream should be applied as early as possible after the start of an infection, ideally during the prodromal period.

7    MARKETING AUTHORISATION HOLDER

Ratiopharm GmbH Graf-Arco-Strasse 3 D-89079 Ulm Germany

8    MARKETING AUTHORISATION NUMBER(S)

PL 15773/0093

9    DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION

15/01/2002

10    DATE OF REVISION OF THE TEXT

03/11/2016