The content of this leaflet was updated according to the guidelines of the Ministry of

Health in April 2019

DERMOVATE OINTMENT
1. Name of the Medicinal Product

Dermovate Ointment

2. Qualitative and Quantitative Composition

Clobetasol 17-propionate 0.05% w/w

Excipients with known effect:

Propylene Glycol

For the full list of excipients, see section 6.1

3. Pharmaceutical Form

Ointment

Clinical Particulars
4.1 Therapeutic Indications

Clobetasol is a very potent topical corticosteroid indicated for adults, elderly and
children over 1 year for the short term treatment only of more resistant inflammatory
and pruritic manifestations of steroid responsive dermatoses unresponsive to less potent
corticosteroids .

These include the following:

• Psoriasis (excluding widespread plaque psoriasis)
• Recalcitrant dermatoses
• Lichen planus
• Discoid lupus erythematosus
• Other skin conditions which do not respond satisfactorily to less potent steroids .

4.2 Posology and Method of Administration

Route of administration: Cutaneous

Ointments are especially appropriate for dry, lichenified or scaly lesions.

Adults, Elderly and Children over 1 year
Apply thinly and gently rub in using only enough to cover the entire affected
area once or twice a day until improvement occurs (in the more responsive
conditions this may be within a few days), then reduce the frequency of
application or change the treatment to a less potent preparation. Allow
adequate time for absorption after each application before applying an
emollient.

Repeated short courses of clobetasol propionate may be used to control

exacerbations.

In more resistant lesions, especially where there is hyperkeratosis, the effect of

clobetasol can be enhanced, if necessary, by occluding the treatment area with
polythene film. Overnight occlusion only is usually adequate to bring about a
satisfactory response. Thereafter improvement can usually be maintained by
application without occlusion.

If the condition worsens or does not improve within 2-4 weeks, treatment and
diagnosis should be re-evaluated.

Treatment should not be continued for more than 4 weeks. If continuous

treatment is necessary, a less potent preparation should be used.

The maximum weekly dose should not exceed 50gr/week.

Therapy with clobetasol should be gradually discontinued once control is

achieved and an emollient continued as maintenance therapy.

Rebound of pre-existing dermatoses can occur with abrupt discontinuation of

clobetasol.

Recalcitrant dermatoses

Patients who frequently relapse

Once an acute episode has been treated effectively with a continuous course of
topical corticosteroid, intermittent dosing (once daily, twice weekly, without
occlusion) may be considered. This has been shown to be helpful in reducing
the frequency of relapse.

Application should be continued to all previously affected sites or to known

sites of potential relapse. This regimen should be combined with routine daily
use of emollients. The condition and the benefits and risks of
continued treatment must be re-evaluated on a regular basis.

Paediatric population
Dermovate is contraindicated in children under one year of age.

Children are more likely to develop local and systemic side effects of topical
corticosteroids and, in general, require shorter courses and less potent agents
than adults.

Care should be taken when using clobetasol propionate to ensure the amount
applied is the minimum that provides therapeutic benefit.
 Duration of treatment for children and infants
Courses should be limited if possible to five days and reviewed weekly.
Occlusion should not be used.

Application to the face

Courses should be limited to five days if possible and occlusion should not be
used.

Elderly
Clinical studies have not identified differences in responses between the
elderly and younger patients. The greater frequency of decreased hepatic or
renal function in the elderly may delay elimination if systemic absorption
occurs. Therefore the minimum quantity should be used for the shortest
duration to achieve the desired clinical benefit.

Renal / Hepatic Impairment

In case of systemic absorption (when application is over a large surface area
for a prolonged period) metabolism and elimination may be delayed therefore
increasing the risk of systemic toxicity. Therefore the minimum quantity
should be used for the shortest duration to achieve the desired clinical benefit.

4.3 Contraindications

Hypersensitivity to the active substance or to any of the excipients listed in

section 6.1.

The following conditions should not be treated with clobetasol:

 Untreated cutaneous infections (fungal, bacterial, viral)

 Rosacea

 Acne vulgaris

 Pruritus without inflammation.

 Perianal and genital pruritus

 Perioral dermatitis

Clobetasol is contraindicated in dermatoses in children under one year of age,

including dermatitis and nappy eruptions.

4.4 Special Warnings and Precautions for Use

Clobetasol should be used with caution in patients with a history of local

hypersensitivity to other corticosteroids or to any of the excipients in the
preparation. Local hypersensitivity reactions (see section 4.8) may resemble
symptoms of the condition under treatment.
Manifestations of hypercortisolism (Cushing’s syndrome) and reversible
hypothalamic-pituitary-adrenal (HPA) axis suppression, leading to
glucocorticosteroid insufficiency, can occur in some individuals as a result of
increased systemic absorption of topical steroids. If either of the above are
observed, withdraw the drug gradually by reducing the frequency of
application, or by substituting a less potent corticosteroid. Abrupt withdrawal
of treatment may result in glucocorticosteroid insufficiency (see section 4.8).

Risk factors for increased systemic effects are:

 Potency and formulation of topical steroid

 Duration of exposure

 Application to a large surface area

 Use on occluded areas of skin (e.g. on intertriginous areas or under

occlusive dressings(in infants the nappy may act as an occlusive dressing)

 Increasing hydration of the stratum corneum

 Use on thin skin areas such as the face

 Use on broken skin or other conditions where the skin barrier may be
impaired

 In comparison with adults, children and infants may absorb proportionally

larger amounts of topical corticosteroids and thus be more susceptible to
systemic adverse effects. This is because children have an immature skin
barrier and a greater surface area to body weight ratio compared with
adults.

Paediatric population
In infants and children under 12 years of age, long-term continuous topical
corticosteroid therapy should be avoided where possible, as adrenal
suppression can occur.

Children are more susceptible to develop atrophic changes with the use of
topical corticosteroids.

Duration of treatment for children and infants

Courses should be limited if possible to five days and reviewed weekly.
Occlusion should not be used.

Infection risk with occlusion

Bacterial infection is encouraged by the warm, moist conditions within skin
folds or caused by occlusive dressings. When using occlusive dressings, the skin
should be cleansed before a fresh dressing is applied.

Use in Psoriasis
Topical corticosteroids should be used with caution in psoriasis as rebound
relapses, development of tolerances, risk of generalised pustular psoriasis and
development of local or systemic toxicity due to impaired barrier function of
 the skin have been reported in some cases. If used in psoriasis careful patient
supervision is important.

Concomitant infection
Appropriate antimicrobial therapy should be used whenever treating
inflammatory lesions which have become infected. Any spread of infection
requires withdrawal of topical corticosteroid therapy and administration of
appropriate antimicrobial therapy.

Chronic leg ulcers

Topical corticosteroids are sometimes used to treat the dermatitis around
chronic leg ulcers. However, this use may be associated with a higher
occurrence of local hypersensitivity reactions and an increased risk of local
infection.

Application to the face

Application to the face is undesirable as this area is more susceptible to atrophic
changes.

If used on the face, treatment should be limited to only 5 days.

Application to the eyelids

If applied to the eyelids, care is needed to ensure that the preparation does not
enter the eye, as cataract and glaucoma might result from repeated exposure. If
clobetasone does enter the eye, the affected eye should be bathed in copious
amounts of water.

Visual disturbance
Visual disturbance may be reported with systemic and topical corticosteroid use.
If a patient presents with symptoms such as blurred vision or other visual
disturbances, the patient should be considered for referral to an ophthalmologist
for evaluation of possible causes which may include cataract, glaucoma or rare
diseases such as central serous chorioretinopathy (CSCR) which have been
reported after use of systemic and topical corticosteroids.

Healthcare professionals should be aware that if this product comes into contact
with dressings, clothing and bedding, the fabric can be easily ignited with a
naked flame. Patients should be warned of this risk and advised to keep away
from fire when using this product.

Dermovate Ointment contains propylene glycol which may cause skin irritation.

4.5 Interaction with other medicinal products and other forms of Interaction

Co-administered drugs that can inhibit CYP3A4 (eg ritonavir and itraconazole)
have been shown to inhibit the metabolism of corticosteroids leading to
increased systemic exposure. The extent to which this interaction is clinically
relevant depends on the dose and route of administration of the corticosteroids
and the potency of the CYP3A4 inhibitor.

4.6. Fertility, pregnancy and lactation

 Pregnancy
There are limited data from the use of clobetasol in pregnant women.

Topical administration of corticosteroids to pregnant animals can cause

abnormalities of foetal development (see Nonclinical Information)

The relevance of this finding to humans has not been established.

Administration of clobetasol during pregnancy should only be considered if the
expected benefit to the mother outweighs the risk to the foetus. The minimum
quantity should be used for the minimum duration.

Breast-feeding
The safe use of topical corticosteroids during lactation has not been established.

It is not known whether the topical administration of corticosteroids could result

in sufficient systemic absorption to produce detectable amounts in breast milk.
Administration of clobetasol during lactation should only be considered if the
expected benefit to the mother outweighs the risk to the infant.

If used during lactation clobetasol should not be applied to the breasts to avoid
accidental ingestion by the infant.

Fertility
There are no data in humans to evaluate the effect of topical corticosteroids on
fertility

Clobetasol administered subcutaneously to rats had no effect upon mating

performance; however, fertility was decreased at the highest dose (see section
5.2).

4.7 Effects on ability to drive and use machines

There have been no studies to investigate the effect of clobetasol on driving

performance or the ability to operate machinery. A detrimental effect on such
activities would not be anticipated from the adverse reaction profile of topical
clobetasol.

4.8 Undesirable effects

Adverse drug reactions (ADRs) are listed below by MedDRA system organ
class and by frequency. Frequencies are defined as: very common (≥1/10),
common (≥1/100 and <1/10), uncommon (≥1/1,000 and <1/100), rare
(≥1/10,000 and <1/1,000) and very rare (<1/10,000), including isolated reports.

Post-marketing data

Infections and Infestations

Very rare Opportunistic infection

Immune System Disorders

Very rare Hypersensitivity, generalised rash

 Endocrine Disorders

Very rare Hypothalamic-pituitary adrenal (HPA) axis suppression:

Cushingoid features: (e.g. moon face, central obesity),
delayed weight gain/growth retardation in children,
osteoporosis, glaucoma, hyperglycaemia/glucosuria,
cataract, hypertension, increased weight/obesity,
decreased endogenous cortisol levels, alopecia,
trichorrhexis

Skin and Subcutaneous Tissue Disorders

Common Pruritus, local skin burning /skin pain

Uncommon Skin atrophy*, striae*, telangiectasias*

Very rare Skin thinning*, skin wrinkling*, skin dryness*, pigmentation

changes*, hypertrichosis, exacerbation of underlying symptoms,
allergic contact dermatitis/dermatitis, pustular psoriasis,
erythema, rash, urticaria, acne

*Skin features secondary to local and/or systemic effects of hypothalamic-

pituitary adrenal (HPA) axis suppression.

General Disorders and Administration Site Conditions

Very rare Application site irritation/pain

Eye disorders

Not known Vision, blurred

Reporting of suspected adverse reactions

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.
Any suspected adverse events should be reported to the Ministry of Health
according to the National Regulation by using an online form
(http://forms.gov.il/globaldata/getsequence/getsequence.aspx?formType=Adv
ersEffectMedic@moh.gov.il).
Additionally, you should also report to GSK Israel (il.safety@gsk.com).

4.9 Overdose

Symptoms
Topically applied clobetasol may be absorbed in sufficient amounts to produce
systemic effects. Acute overdosage is very unlikely to occur, however, in the
case of chronic overdosage or misuse the features of hypercortisolism may
occur (see section 4.8).
 Management
In the event of overdose, clobetasol should be withdrawn gradually by reducing
the frequency of application or by substituting a less potent corticosteroid
because of the risk of glucocorticosteroid insufficiency.
Further management should be as clinically indicated or as recommended by
the national poisons centre, where available.

Pharmacological Properties

5.1 Pharmacodynamic Properties

Pharmacotherapeutic group: Corticosteroids, very potent (group IV)

ATC code: D07AD

Mechanism of action
Topical corticosteroids act as anti-inflammatory agents via multiple
mechanisms to inhibit late phase allergic reactions including decreasing the
density of mast cells, decreasing chemotaxis and activation of eosinophils,
decreasing cytokine production by lymphocytes, monocytes, mast cells and
eosinophils, and inhibiting the metabolism of arachidonic acid.

Pharmacodynamic effects
Topical corticosteroids have anti-inflammatory, antipruritic, and
vasoconstrictive properties.

5.2 Pharmacokinetic properties

Absorption
Topical corticosteroids can be systemically absorbed from intact healthy skin.
The extent of percutaneous absorption of topical corticosteroids is determined
by many factors, including the vehicle and the integrity of the epidermal
barrier. Occlusion, inflammation and/or other disease processes in the skin
may also increase percutaneous absorption.

Mean peak plasma clobetasol propionate concentrations of 0.63 nanograms/ml

occurred in one study eight hours after the second application (13 h after an
initial application) of 30 g clobetasol propionate 0.05 % ointment to normal
individuals with healthy skin. Following the application of a second dose of
30 g clobetasol propionate cream 0.05 %, mean peak plasma concentrations
were slightly higher than the ointment and occurred 10 h after application. In a
separate study, mean peak plasma concentrations of approximately
2.3 nanograms/ml and 4.6 nanograms/ml occurred respectively in patients with
psoriasis and eczema three hours after a single application of 25 g clobetasol
propionate 0.05 % ointment.

Distribution
The use of pharmacodynamic endpoints for assessing the systemic exposure of
topical corticosteroids is necessary due to the fact that circulating levels are
well below the level of detection.
 Metabolism
Once absorbed through the skin, topical corticosteroids are handled through
pharmacokinetic pathways similar to systemically administered
corticosteroids. They are metabolised, primarily in the liver.

Elimination
Topical corticosteroids are excreted by the kidneys. In addition, some
corticosteroids and their metabolites are also excreted in the bile.

5.3 Preclinical safety data

Carcinogenesis / Mutagenesis

Carcinogenesis
Long-term animal studies have not been performed to evaluate the carcinogenic
potential of clobetasol propionate.

Genotoxicity
Clobetasol propionate was not mutagenic in a range of in vitro bacterial cell
assays.

Reproductive Toxicology

Fertility
In fertility studies, subcutaneous administration of clobetasol propionate to rats
at doses of 6.25 to 50 micrograms/kg/day produced no effects on mating, and
fertility was only decreased at 50 micrograms/kg/day.

Pregnancy
Subcutaneous administration of clobetaol propionate to mice (100
micrograms/kg/day), rats (400 micrograms/kg/day) or rabbits (1 to 10
micrograms/kg/day) during pregnancy produced foetal abnormalities including
cleft palate and intrauterine growth retardation.

In the rat study, where some animals were allowed to litter, developmental delay
was observed in the F1 generation at 100 micrograms/kg/day and survival was
reduced at 400 micrograms/kg/day. No treatment-related effects were observed
in F1 reproductive performance or in the F2 generation.

Pharmaceutical Particulars
6.1 List of Excipients

Propylene glycol
Sorbitan sesquioleate
White soft paraffin

6.2 Incompatibilities

None known.
6.3 Shelf Life

The expiry date of the product is indicated on the label and packaging.
Use within 3 months after opening.

6.4 Special Precautions for Storage

Store below 25°C.

6.5 Nature and Contents of Container

Membrane-sealed, collapsible, aluminium tubes either coated internally with

epoxy resin based lacquer or uncoated sealed with a latex band sealant and
wadless polypropylene caps.

Pack sizes: 25 g, 30 g or 100 g.

Not all pack sizes may be marketed

6.6 Special precautions for disposal and other handling

Patients should be advised to wash their hands after applying Dermovate

Ointment unless it is the hands that are being treated.

7. Manufacturer

Glaxo Operations (UK) Limited, Barnard Castle, UK.

8. License Holder and Importer

GlaxoSmithKline (Israel) Ltd., 25 Basel St., Petach Tikva

9. License Number

027-57-22063

The format of this leaflet was determined by the Ministry of Health and its content was checked and approved in April 2019

Trade marks are owned by or licensed to the GSK group of companies.

©2019 GSK group of companies or its licensor

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