ASDA COLD SORE 5% W/W CREAM, COLDSORZ ACICLOVIR 5% W/W CREAM, COLD SORE CREAM ACICLOVIR 5% - summary of medicine characteristics

Cold Sore Cream Aciclovir 5%

Wilko Cold Sore Cream Aciclovir 5% w/w

Asda Cold Sore 5% w/w Cream

2 QUALITATIVE AND QUANTITATIVE COMPOSITION

1g of Cream contains 50mg aciclovir.

For excipients see 6.1

3 PHARMACEUTICAL FORM

Cream.

White to off-white cream.

4 CLINICAL PARTICULARS

4.1 Therapeutic indications

Cold Sore Cream Aciclovir 5% is indicated in adults and children for the initial and recurrent treatment of herpes labialis. For topical use within 24 hours of onset of prodromal symptoms. Do not use in the eyes.

Immunocompromised Patients

Cold Sore Cream Aciclovir 5% 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 administration

Route of administration – Topical

For cutaneous use.

Cold Sore Cream Aciclovir 5% treatment should be initiated as soon as possible after the start of the infection, ideally during the prodromal or erythema period or when the lesions first appear.

A thin film of Cold Sore Cream Aciclovir 5% should be applied to the infected and immediately adjacent skin areas 5 times daily, at 4 hour intervals omitting the night time application. Treatment should be continued for 4 days. If the cold sore or sores have not healed after this time, the cream can be used for a further 5 days.

If the infection persists or gets worse, the patient should stop using Cold Sore Cream Aciclovir 5% and consult a doctor.

Use in the Elderly

No special comment

4.3 Contraindi­cations

Cold Sore Cream Aciclovir 5% is contraindicated in patients known to be hypersensitive to aciclovir, valaciclovir, propylene glycol or any of the excipients of Cold Sore Cream Aciclovir 5%.

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.

In severely immune-compromised patients (e.g. AIDS patients or bone marrow transplant recipients) oral aciclovir 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).

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

4.5 Interaction with other medicinal products and other forms of interaction

No clinically significant interactions have been identified.

Probenecid increases the mean half-life and area under the plasma concentration curve of the 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 aciclovir.

4.6 Fertility, Pregnancy and lactation

Fertility

See Clinical Studies in section 5.2

Pregnancy

No specific studies of topical aciclovir have been carried out in pregnant women or nursing mothers. 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 5% is very low 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 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.

Lactation

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 Cold Sore Cream Aciclovir 5% would be insignificant.

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.

Clinical trial data have been used to assign frequency categories to adverse reactions observed during clinical trials with aciclovir 5% cream. 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.

Skin and subcutaneous tissue disorders

Uncommon: Transient burning or stinging following application of Cold Sore Cream Aciclovir 5%.

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.

Immune system disorders

Very rare:      Immediate hypersensitivity reactions including angioedema and urticaria.

Reporting of suspected adverse reactions

Reporting of 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 5% cream.

No untoward effects would be expected if the entire contents of a 2g tube of Cold Sore Cream Aciclovir 5% containing 100mg of aciclovir were ingested orally or applied topically.

Aciclovir is dialysable by haemodialysis.

5 PHARMACOLOGICAL PROPERTIES

5.1 Pharmacodynamic properties

Aciclovir is a pharmacologically inactive substance. After penetration into cells which are infected with herpes simplex virus types I and II (HSV I & HSV II) or varicella-zoster virus (VZV), aciclovir is converted into a virostatic agent. The conversion of aciclovir is catalysed by viral HSV- or VZV-thymidine kinase. Human thymidine kinase does not use aciclovir effectively as a substrate, hence the toxicity to mammalian host cells is low.

In the infected cell, aciclovir is phosphorylated by viral thymidine kinase to aciclovir monophosphate, which is further converted by cellular enzymes to aciclovir triphosphate. Aciclovir triphosphate has a greater affinity for viral DNA polymerase than host cell DNA polymerase and therefore selectively interferes with the viral enzyme causing inhibition of viral DNA replication. Aciclovir is also incorporated into viral DNA by viral DNA polymerase, which results in chain termination, as aciclovir lacks a 3’-hydroxyl group, preventing addition of nucleotides by 3’-5’-linkage.

In severely immunocompromised patients a longer or repeated treatment with aciclovir can lead to a selection of viral strains with reduced sensitivity. As a result, these patients no longer respond to treatment with aciclovir. Most of the clinical isolates with reduced sensitivity showed a relative lack of virus thymidine kinase. However strains with changed/different virus thymidine kinase or DNA polymerase were also reported. The in vitro exposition of HSV-isolates can also lead to the development of less sensitive strains. The connection between the in vitro determined sensitivity of HSV-isolates and the clinical response to treatment with aciclovir is not clear.

5.2 Pharmacokinetic properties

Absorption and plasma concentrations

Aciclovir penetrates into the skin. The intracutaneous concentration levels are higher than the minimal inhibitory concentration (MIC) in tissue at steady state.

After topical application of aciclovir, no aciclovir plasma concentrations could be determined.

As the aciclovir plasma concentrations following topical application are below the limit of detection, no pharmacokinetic studies are available on topical aciclovir. Therefore, the following data is based on the data after oral or intravenous administration.

Plasma protein binding is reported to range between 9 and 33% as a function of dose. The volume of distribution at steady state in adults is 50 ± 8.7 1/1.73 m2, or 0.7 l/kg.

Two metabolites could be identified in the urine of patients with normal renal function after single dosing with 14C-aciclovir: 9-carboxymethoxy­methylguanine (2–4% of an administered dose) and 8-hydroxy-9-(2-hydroxyethoxy­methyl)guanine (< 0.2% of a dose). Subjects with normal renal function eliminate 62–91% of an aciclovir dose unchanged and 9–14% as 9-carboxymethoxy­methyl)guanine via the kidneys.

Aciclovir is predominantly eliminated via the kidneys, primarily by glomerular filtration and to a lesser extent by tubular secretion.

In vitro and in vivo studies of aciclovir cream and aciclovir ointment versus oral aciclovir were carried out to determine the bioavailability of aciclovir in human skin. The in vitro studies used human skin biopsates, whilst the bioassays either used human skin grafts on mice or were carried out in the human eye (3 patients). The following dermal drug concentration gradient emerged for both topical and oral aciclovir: stratum corneum > epidermis > dermis. There was no difference in concentration between cream and ointment.

The upper layers of the epidermis on average showed a 48-fold higher concentration following topical application of aciclovir ointment or cream 5% than after oral dosing, but the drug concentration in the basal epidermis – the site of herpes virus infection – was 2 to 3 times lower following topical application than after oral dosing.

On the basis of continuous absorption the concentration increased as a function of time (higher drug concentrations being found 48 hours post topical dose than 24 hours post topical dose). Thus short dosing intervals appear rational for the topical treatment of herpes simplex virus (HSV) infections.

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.

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.

5.3 Preclinical safety data

For 24 days, PEG-based Aciclovir Cream 5 or 10% was applied to the shaved (intact and grazed) skin of guinea-pigs. The treated area corresponded to 10% of the body surface. There were neither systemic nor local toxic symptoms. This is also confirmed by histologic studies and autopsy. According to the test carried out by Draize, who evaluated the allergic sensitising potential of a substance there were no pathologic findings.

Studies carried out in swine showed that 5% aciclovir cream in a PEG vehicle caused an only minimal (quantitative) delay in epidermal wound healing.

Rabbits had 1, 3 or 6% aciclovir cream in a white petroleum vehicle introduced directly into both eyes 5 times daily at 90-minute intervals for 3 weeks. Neither autopsy nor inspection nor histological examination revealed any pathological changes in the rabbit eyes.

6 PHARMACEUTICAL PARTICULARS

6.1 List of excipients

PEG-5-glycerol-stearate

Dimeticone

Cetyl alcohol

Liquid paraffin

White soft paraffin

Propylene glycol

Purified water

6.2 Incompatibilities

None.

6.3 Shelf life

3 years unopened.

6 weeks after first opening of container.

6.4 Special precautions for storage

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

6.5 Nature and contents of container

The cream is filled into aluminium tubes fitted with a polyethylene screw cap.

Individual tubes are packed into a carton with a patient information leaflet.

Pack sizes:

Cold Sore Cream Aciclovir 5%:       Tubes of 2g

6.6 Special precautions for 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.