Zovirax Cream 5%
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Zovirax Cream
2. Qualitative and Quantitative Composition
Aciclovir BP 5.0% w/w
For the full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Topical Cream
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Zovirax Cream is indicated for the treatment of Herpes Simplex virus infections of the skin including initial and recurrent genital herpes and herpes labialis.
Route of administration: topical.
Do not use in eyes.
4.2 Posology and method of administration
Adults and Children: Zovirax Cream should be applied five times daily at approximately four hourly intervals, omitting the night time application.
Zovirax 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 occured then treatment may be continued for up to an additional 5 days.
Use in the elderly: No special comment
4.3 Contraindications
Zovirax Cream is contraindicated in patients known to be hypersensitive to aciclovir, valaciclovir, propylene glycol or any of the excipients of Zovirax Cream listed in section 6.1.
4.4 Special warnings and precautions for use
Zovirax 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.
In severely immunocompromised patients (eg AIDS patients or bone marrow transplant recipients) oral Zovirax dosing should be considered. Such patients 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).
Zovirax Cream contains a specially formulated base and should not be diluted or used as a base for the incorporation of other medicaments.
4.5 Interaction with other medicinal products and other forms of interaction
No clinically significant interactions have been identified.
4.6. Fertility, pregnancy and breast-feeding
Pregnancy:
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 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 Zovirax 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 Zovirax 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 Zovirax 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 1g 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
Not applicable
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 Zovirax 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.
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 a 10 gram tube of Zovirax Cream containing 500mg of aciclovir 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
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, Zovirax Cream 5% was compared to vehicle cream. In these studies, time from start of treatment to healing was 4.6 days using Zovirax Cream and 5.0 days using vehicle cream (p<0.001). Duration of pain was 3.0 days after start of treatment in the Zovirax 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.
Pharmacokinetic properties
5.2
Pharmacology studies have shown only minimal systemic absorption of aciclovir following repeated topical administration of Zovirax 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
Poloxamer 407 Cetostearyl alcohol Sodium lauryl sulfate White soft paraffin Liquid paraffin Propylene glycol Purified water
Arlacel 165 (containing glycerol monostearate and polyoxyethylene stearate)
Dimeticone 20
6.2 Incompatibilities
None known.
6.3
Shelf life
3 years
6.4 Special precautions for storage
Store below 25°C. Do not refrigerate.
6.5 Nature and contents of container
Collapsible aluminium tubes with plastic screw caps Pack size: 2g or 10g tubes
6.6. Special precautions for disposal
No special requirements.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
7 MARKETING AUTHORISATION HOLDER
The Wellcome Foundation Ltd
980 Great West Road
Brentford
Middlesex
TW8 9GS
United Kingdom
Trading as
GlaxoSmithKline UK Stockley Park West Uxbridge
Middlesex UB11 1BT
8. MARKETING AUTHORISATION NUMBER
PL 00003/0180
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: 28 October 1999 Date of latest renewal: 28 October 2004
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DATE OF REVISION OF THE TEXT
11/12/2013