Etrivex 500 Micrograms/G Shampoo
SUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Etrivex 500 micrograms/g shampoo
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
One gram of shampoo contains 500 micrograms of clobetasol propionate.
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Shampoo.
Viscous, translucent, colourless to pale yellow liquid shampoo with alcoholic odour.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Topical treatment of moderate scalp psoriasis in adults.
4.2 Posology and method of administration
For cutaneous use on the scalp only.
Etrivex 500 micrograms/g shampoo should be applied directly on dry scalp once daily taking care to well cover and massage the lesions. An amount equivalent to around a half tablespoon (around 7.5 ml) per application is sufficient to cover all the scalp. Etrivex 500 micrograms/g shampoo should be then kept in place without covering for 15 minutes before rinsing. Hands should be washed carefully after application. After 15 minutes, the product must be rinsed with water and / or hair can be washed by using an additional amount of regular shampoo if needed to facilitate washing. Then, hair can be dried as usual.
The treatment duration should be limited to a maximum of 4 weeks. As soon as clinical results are observed, applications should be spaced out or replaced, if needed, by an alternative treatment. If no improvement is seen within four weeks, reassessment of the diagnosis may be necessary.
Repeated courses of Etrivex 500 micrograms/g shampoo may be used to control exacerbations provided the patient is under regular medical supervision.
Paediatric population
The experience in the paediatric population is limited. Etrivex 500 micrograms/g shampoo is not recommended for use in children and adolescents below 18 years of age. It is contraindicated in children under 2 years of age (see sections 4.3 and 4.4).
4.3 Contraindications
- Hypersensitivity to the active substance or to any of the excipients
- Skin areas affected by bacterial, viral (varicella, herpes simplex, herpes zoster), fungal or parasitic infections and specific skin diseases (skin tuberculosis, skin diseases caused by lues).
- Etrivex 500 micrograms/g shampoo must not be applied to the eye (risk of glaucoma) or to ulcerous wounds.
- Children under 2 years of age
4.4 Special warnings and precautions for use
Topical corticosteroids should be used with caution for a number of reasons including post treatment rebound relapses, development of tolerance (tachyphylaxis) and development of local or systemic toxicity. In rare instances, treatment of psoriasis with corticosteroids (or its withdrawal) is thought to have provoked generalised pustular psoriasis in case of intensive and prolonged topical use. In very rare cases, hypersensitivity to corticosteroids can be observed. This can be suspected in case of resistance to treatment.
In general, long-term continuous therapy with corticosteroids, use of occlusive mobcaps or treatment of children can lead to a higher risk of systemic effects. In such cases, medical supervision should be increased and patients may be evaluated periodically for evidence of HPA axis suppression. Such systemic effects disappear when treatment is stopped. However, abrupt discontinuation can lead to acute adrenal insufficiency, especially in children. If Etrivex 500 micrograms/g shampoo is required for use in children and adolescents below 18 years of age, it is recommended that the treatment should be reviewed weekly.
Etrivex 500 micrograms/g shampoo is only intended for the treatment of scalp psoriasis and should not be used to treat other skin areas. In particular, Etrivex 500 micrograms/g shampoo is not recommended for use in the face, eyelids, intertriginous areas (axillae and genitoanal regions) and on other erosive skin surfaces as this could increase the risk of topical adverse events such as atrophic changes, telangectasia or cortico-induced dermatitis.
If Etrivex 500 micrograms/g shampoo does enter the eye, the affected eye should be rinsed with copious amounts of water.
4.5 Interaction with other medicinal products and other forms of interaction
No interaction studies have been performed
4.6 Pregnancy and lactation
Pregnancy
There are no adequate data from the use of topical clobetasol propionate in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). The potential risk for humans is unknown.
Etrivex 500 micrograms/g shampoo should not be used during pregnancy unless clearly necessary.
Lactation
Systemically administered corticosteroids pass into breast milk. Damage to the infant is not reported to date. Nevertheless, as there are no adequate data on the possible milk transfer of topical clobetasol propionate and its biological or clinical repercussions, Etrivex 500 micrograms/g shampoo should not be prescribed to breastfeeding women unless clearly indicated.
4.7 Effects on ability to drive and use machines
As a topical corticosteroid, Etrivex 500 micrograms/g shampoo has no or negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
During clinical development of Etrivex 500 micrograms/g shampoo, in a total of 558 patients receiving Etrivex 500 micrograms/g shampoo, the most commonly reported adverse drug reaction was skin discomfort. Its incidence was about 5%. Most adverse events were rated as mild to moderate and they were not affected by race or gender. Clinical signs of irritation were uncommon (0.5%). No serious drug-related adverse events were reported during any of the clinical trials.
If signs of local intolerance appear, application should be suspended until they disappear. If signs of hypersensitivity appear, application should be stopped immediately.
The table below reports the adverse reactions related to treatment by body system and by absolute frequency:
|
Body System |
Incidence |
Adverse Reactions |
|
Skin and subcutaneous tissue disorders |
Common (> 1/100 , < 1/10) |
Skin discomfort Acne/follicultis |
|
Uncommon (> 1/1000, <1/100) |
Local signs of irritation Pruritus Urticaria Telangiectasia Skin atrophy | |
|
Eye disorders |
Common (> 1/100 , < 1/10) |
Eye stinging/burning |
As a class attribution, prolonged use of topical corticosteroids, treatment of extensive areas or use of large amounts can result in sufficient systemic absorption to produce the features of hypercortisolism (Cushing syndrome) or of Hypothalamus-Pituitary-Adrenal (HPA) axis suppression. Should HPA axis suppression occur, it is likely to be transient with a rapid return to normal values. However, as Etrivex 500 micrograms/g shampoo is to be kept in place for only 15 minutes before rinsing, systemic absorption is seldom observed (see section 5.2) and therefore, the risk of appearance of HPA axis suppression is very low compared to non rinsed potent corticosteroids products. No HPA axis suppression has been observed during clinical trials with Etrivex 500 micrograms/g shampoo.
Prolonged and/or intensive treatment with potent corticosteroid preparations may cause local atrophic changes, such as local skin atrophy, striae, telangiectasia, erythema, purpura, contact dermatitis. When applied to the face, very potent corticosteroids can induce perioral dermatitis, skin atrophy or worsen rosacea. During development of Etrivex 500 micrograms/g shampoo, skin atrophy was assessed using ultrasound measurement of skin thickness in a specific clinical trial involving 13 patients. After 4 weeks of treatment with Etrivex 500 micrograms/g shampoo, no skin thinning was observed.
There are reports of pigmentation changes, acne, pustular eruptions and hypertrichosis with topical corticosteroids.
4.9 Overdose
Acute overdose is very unlikely to occur, however, in the case of chronic overdose or misuse, the features of hypercortisolism may appear and in this situation, treatment should be discontinued gradually. However, because of the risk of acute adrenal suppression, this should be done under medical supervision.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Corticosteroids, Very Potent (Group IV)
ATC code: D07AD01
Like other topical corticosteroids, clobetasol propionate has antiinflammatory, antipruritic, and vasoconstrictive properties. The mechanism of the anti-inflammatory activity of topical corticosteroids in general is unclear. However, corticosteroids are thought to act by induction of phospholipase A2 inhibitory proteins, collectively called lipocortins. It is postulated that these proteins control the biosynthesis of potent mediators of inflammation such as prostaglandins and leukotrienes by inhibiting the release of their common precursor, arachidonic acid. Arachidonic acid is released from membrane phospholipids by phospholipase A2.
5.2 Pharmacokinetic properties
In vitro liberation -penetration studies on human skin showed that only a small percentage (0.1 %) of the applied dose of Etrivex Shampoo can be found in the epidermis (including the stratum corneum) when applied for 15 minutes and then rinsed. The very low topical absorption of clobetasol propionate from Etrivex Shampoo when applied according to the recommended clinical use (15 minutes before rinse off) resulted in negligible systemic exposure in animal studies and in clinical trials. Available clinical data revealed that only 1 of 141 subjects had a quantifiable clobetasol propionate plasma concentration (0.43 ng/ml).
The present pharmacokinetic data indicate that systemic effects following clinical treatment with Etrivex Shampoo are highly unlikely due to the low systemic bioavailability of clobetasol propionate.
Preclinical safety data
5.3
Non clinical data reveal no special hazard for humans based on conventional studies of safety pharmacology, single, repeated dose toxicity and genotoxicity. The carcinogenicity of clobetasol has not been studied.
In rabbits, Etrivex Shampoo was slightly irritating to the skin and eyes, but no delayed-type hypersensitivity was seen on guinea pigs’ skin.
In developmental toxicity studies in the rabbit and the mouse, clobetasol propionate was shown to be teratogenic when administered subcutaneously at low doses In a topical embryotoxicity study of clobetasol in the rat, foetal immaturity and skeletal and visceral malformations were observed at relatively low dosage levels. In addition to malformations, studies in animals exposed to high systemic levels of glucocorticoids during pregnancy have also shown other effects on the offspring, such as intrauterine growth retardation.
The clinical relevance of the effects of clobetasol and other corticosteroids in developmental animal studies is unknown.
6 PHARMACEUTICAL PARTICULARS
6.1 List of excipients
Ethanol
Coco alkyl dimethyl betaine Sodium laurethsulfate Polyquaternium-10 Sodium citrate Citric acid monohydrate Purified water
6.2 Incompatibilities
Not applicable
6.3
Shelf life
3 years
Shelf life after first opening: 4 weeks
6.4 Special precautions for storage
Store in the original container
6.5 Nature and contents of container
The product is packaged in high density polyethylene (HDPE) bottles of 60 ml or 125 ml fitted with polypropylene snap closures. The HDPE bottle of 30 ml is fitted with polypropylene screw closure.
Bottles contain 30 ml, 60 ml or 125 ml of shampoo.
1 g of shampoo corresponds to 1 millilitre of shampoo.
Not all pack sizes may be marketed.
6.6 Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Galderma (UK) Limited Meridien House 69-71 Clarendon Road Watford Herts
WD17 1DS,
UK
8 MARKETING AUTHORISATION NUMBER(S)
PL 10590/0052
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
28/11/2011
10 DATE OF REVISION OF THE TEXT
28/11/2011