Xerclear
SUMMARY OF PRODUCT CHARACTERISTICS
1. NAME OF THE MEDICINAL PRODUCT
Xerclear 50 mg/g and 10 mg/g cream
2. QUALITATIVE AND QUANTITATIVE COMPOSITION
1 gram cream contains 50 mg aciclovir and 10 mg hydrocortisone.
Excipients with known effect: 67,5 mg cetostearyl alcohol and 200 mg propylene glycol / gram cream.
For the full list of excipients, see section 6.1.
3. PHARMACEUTICAL form
Cream
White to yellowish cream
4. Clinical particulars
4.1 Therapeutic indications
Treatment of early signs and symptoms of recurrent herpes labialis (cold sores) to reduce the progression of cold sore episodes to ulcerative lesions in immunocompetent adults and adolescents (12 years of age and older).
Posology and method of administration
Posology
Adults and adolescents (12 years of age and older)
Xerclearshould be applied 5 times per day for 5 days, approximately every 3-4 hours during the awake time of the day. Treatment should be initiated as early as possible, preferably immediately after the first signs or symptoms. A sufficient quantity of the cream shall be applied each time to cover all lesions including their outer margin.
Paediatric population
The safety and efficacy of Xerclearin children below 12 years have not yet been established
Method of administration
Cutaneous use only.
4.3 Contraindications
Hypersensitivity to the active substances, valaciclovir or to any of the excipients listed in 6.1.
Use for skin lesions caused by virus other than herpes simplex, or for fungal, bacterial or parasitic skin infections.
4.4 Special warnings and precautions for use
Xerclearis intended for cutaneous use only on herpes labialis on the lips and face. The cream should not be used for application to mucous membranes (e.g. in the eye or inside the mouth, nose or on the genitals).
The cream should not be used in severely immunocompromised patients such as hiv-patients or transplanted patients, since an increased risk for development of resistance to aciclovir can not be excluded in these patients.
Treatment of patients with concomitant dermatitis of other origin has not been studied.
This cream contains cetostearyl alcohol which may cause local skin reactions (e.g. contact dermatitis) and propylene glycol which may cause skin irritation .
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed with Xerclear.
4.6 Fertility, pregnancy and lactation
Pregnancy
There are no adequate data from the use of Xerclearin pregnant women.
No increase in adverse foetal outcomes was reported in prospective studies of approximately 1200 women exposed to systemic aciclovir . Systemic administration of aciclovir in 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.
Topical application of corticosteroids to pregnant animals can cause abnormalities of foetal development including cleft palate and intrauterine growth retardation. There may therefore be a very small risk of such effects in the human foetus.
Xerclearshould not be used during pregnancy unless clearly necessary.
Lactation
Aciclovir and hydrocortisone pass into milk after systemic administration but a risk for adverse reactions in a nursing infant seems unlikely at therapeutic doses as systemic exposure is minimal with topical administration. Xerclearshould however not be used during lactation unless clearly necessary.
Fertility
There are no data in humans to evaluate the effect of Xerclear on fertility.
4.7 Effects on ability to drive and use machines
Xerclearhas no or negligible influence on the ability to drive and use machines.
Undesirable effects
Clinical studies
The majority of the adverse reactions were local and occurred in the area of the application site.
Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥ 1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).
|
System Organ Class |
Adverse Reaction/Event |
Frequency |
|
Skin and subcutaneous tissue disorders |
Drying or flaking of the skin |
Common |
|
Transient burning or tingling following application |
Uncommon |
|
|
Erythema Pigmentation changes Application site reaction including signs and symptoms of inflammation Contact dermatitis following application has been observed when applied under occlusion in dermal safety studies. Where sensitivity tests have been conducted, the reactive substance was hydrocortisone or a component of the cream base. |
Rare |
Additional adverse events related to either of the two active substances, aciclovir and hydrocortisone, should be considered.
Paediatric population
The safety profile in adolescents (12-17 years) was similar to that in adults.
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 national reporting system listed in Appendix V.
4.9 Overdose
No untoward effects would be expected if the entire contents of a tube of Xerclearcream were ingested orally or applied topically due to minimal systemic exposure. In the event of a suspected overdose treatment should be symptomatic.
5. PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Antivirals, ATC code: D06BB53
Xerclearis a combination of aciclovir and hydrocortisone.
Mechanism of action
Aciclovir is an antiviral agent which is highly active in vitro against Herpes Simplex Virus (HSV) types 1 and 2. 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.
Hydrocortisone is the main glucocorticoid secreted by the adrenal cortex. It is used topically for its anti-inflammatory effects which suppress the clinical manifestations of the disease in a wide range of disorders where inflammation is a prominent feature.
Xerclear, which combines the antiviral activity of aciclovir and the anti-inflammatory action of hydrocortisone, reduces the risk for development of ulcerative herpes labialis lesions. The exact mechanism for this is not fully characterized but is thought to be mediated through clearance of the virus and mitigating the local inflammatory response in the lip leading to lessening of the symptoms.
Clinical efficacy and safety
Adults
In a double-blind, randomised clinical study 1443 subjects with recurrent labial herpes were treated either with Xerclearcream, aciclovir 5% in Xerclearvehicle or vehicle alone. The primary endpoint was prevention of progression of cold sores episodes to ulcerative lesions. Among subjects treated with Xerclear58% developed ulcerative lesions compared to 65% in subjects treated with 5% aciclovir in Xerclearvehicle (p=0.014) and 74% in subjects treated with vehicle (p<0.0001). In those subjects that developed ulcerative lesions, the mean episode duration was 5.7, 5.9 and 6.5 days, for Xerclearcream, aciclovir 5% in Xerclearvehicle or vehicle alone.
Paediatric population
An open label safety study in adolescents with recurrent herpes labialis was conducted in 254 subjects between 12-17 years. Therapy was applied using the same dosing regimen as in adults and subjects were followed for adverse events. The safety and efficacy profile was similar to that observed in adults.
Immunocompromised patients
Safety was studied in a randomised, double-blind clinical study in 107 adult subjects with mild to moderate immunosuppression treated with either Xerclearcream or aciclovir in Xerclearvehicle. Safety and frequency of recurrences during a follow-up period of one year after treatment of an HSV recurrence were similar between the two treatment groups.
5.2 Pharmacokinetic properties
No clinical pharmacokinetic studies have been performed with Xerclear.
Absorption
Due to limited absorption, the systemic exposure of aciclovir is expected to be low following topical administration of Xerclear.
Glucocorticoids have the ability to penetrate stratum corneum of the epidermis and affect the deeper cell layers. Usually only a small proportion of the dose is absorbed, and it is thus not expected to affect the hormonal balance. The systemic effect of glucocorticoids can occur in the event of increased absorption, e.g. when applied on large inflamed areas of skin, or on skin of which the stratum corneum of the epidermis is damaged. Occlusive bandages increase absorption.
5.3 Preclinical safety data
Non-clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, repeated dose toxicity, genotoxicity, carcinogenic potential, toxicity to reproduction and development.
6. PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Cetostearyl alcohol,
Liquid paraffin,
Poloxamer 188,
Propylene glycol,
Isopropyl myristate,
Sodium lauryl sulphate,
White soft paraffin,
Citric acid monohydrate,
Sodium hydroxide (for pH adjustments)
Hydrocloric acid (for pH adjustments)
Purified water.
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years
Shelf life after first opening: 12 months
6.4 Special precautions for storage
Store below 25C. Do not refrigerate or freeze.
Nature and contents of container
2 g aluminium laminated polyethylene plastic tube.
5 g aluminium laminated polyethylene plastic tube.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal and other handling
Any unused product or waste material should be disposed of in accordance with local requirements.
7. MARKETING AUTHORISATION HOLDER
Medivir AB
P.O. Box 1086
SE-141 22 Huddinge
Sweden
8. MARKETING AUTHORISATION NUMBER(S)
<[To be completed nationally]>
9. DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
Date of first authorisation: <To be completed nationally>
Date of latest renewal: <To be completed nationally>
10. DATE OF REVISION OF THE TEXT
26 May 2015