For the use only of Registered Medical Practitioners or a Hospital or a Laboratory

EUMOSONE M

1. GENERIC NAME

Clobetasone Butyrate and Miconazole Nitrate Skin Cream

2. QUALITATIVE AND QUANTITATIVE COMPOSITION

Contains:

Clobetasone Butyrate IP 0.05 % w/w

Miconazole Nitrate IP 2.0 % w/w
Chlorocresol IP (as preservative) 0.1 % w/w
in a non greasy base

List of Excipients

Cetostearyl Alcohol, White Bees Wax, Arlacel 165, Dimethicone 20, Glycerin, Chlorocresol,
Sodium Citrate, Citric acid Monohydrate, Finester-1240, Purified Water.

3. DOSAGE FORM AND STRENGTH

Cream

For information on strength(s) refer 2. Qualitative and Quantitative Composition above.

4. CLINICAL PARTICULARS

4.1 Therapeutic Indication

Clobetasone butyrate is a moderately potent topical corticosteroid indicated for adults, elderly,
children and infants for the relief of the inflammatory and pruritic manifestations of steroid
responsive dermatoses. Miconazole nitrate is an imidazole antifungal agent.

Topical preparations combining clobetasone with miconazole are indicated for the treatment
and management of steroid responsive dermatoses where secondary fungal infection is present,
suspected or likely to occur.

These include the following: atopic dermatitis, nappy rash, intertrigo, seborrhoeic dermatitis.

4.2 Posology and Method of Administration

Creams are especially appropriate for moist or weeping surfaces.

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Adults, Elderly, Children and Infants

Apply thinly and gently rub in using only enough to cover the entire affected area twice a day
for up to seven days. If the infection worsens, treatment and diagnosis should be re-evaluated
as soon as possible.

If the condition does not improve within seven days, treatment and diagnosis should be re-
evaluated.

Treatment should not be continued for more than seven days without medical supervision.

Allow adequate time for absorption after each application before applying an emollient.
Patients should be advised to wash their hands after applying EUMOSONE M, unless it is the
hands that are being treated.

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

corticosteroids especially with potent preparations. If further treatment is required to achieve
control of the pre-existing dermatoses, it may be necessary to continue therapy with another
corticosteroid preparation not containing miconazole.

Children

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

Care should be taken when using EUMOSONE M to ensure the amount applied is the minimum
that provides therapeutic benefit.

Elderly

Clinical studies of clobetasone butyrate 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

EUMOSONE M is contra-indicated in untreated primary cutaneous infections, secondary

bacterial and viral cutaneous infections, rosacea, acne vulgaris, pruritus without inflammation
and in people with history of hypersensitivity to any ingredient in the product or to other
imidazole derivatives.

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4.4 Special Warnings and Precautions for Use

Local hypersensitivity reactions (see 4.8 Undesirable Effects) may resemble symptoms of the
condition under treatment.

Severe hypersensitivity reactions, including anaphylaxis and angioedema, have been reported
during treatment with other miconazole topical formulations (see 4.8 Undesirable Effects). If
a reaction suggesting hypersensitivity or irritation should occur, the treatment should be
discontinued.

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 4.8 Undesirable Effects).

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.

Visual disturbance has been reported by patients using systemic and/or topical corticosteroids.
If a patient has blurred vision or other visual disturbances, consider evaluation of possible
causes which may include cataract, glaucoma or central serous chorioretinopathy.

Children

In infants and children under 12 years of age, long-term continuous topical corticosteroid
therapy should be avoided where possible, as adrenal suppression is more likely to occur.

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.

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Application to the face

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

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.

Concomitant bacterial and/or viral infection

Appropriate antimicrobial therapy should be used whenever treating inflammatory lesions

which have bacterial and /or viral infection also. 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.

Accidental ingestion

For external use only. This and all medication should be kept out of the reach of children. In
case of accidental ingestion, professional assistance should be sought or a national poison
control centre contacted immediately (see 4.9 Overdose).

4.5 Drug Interactions

Co-administered drugs that can inhibit CYP3A4 (e.g. ritonavir, 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.

Miconazole administered systemically is known to inhibit CYP3A4/2C9. Due to the limited

systemic availability after topical application, clinically relevant interactions are rare.
However, in patients on oral anticoagulants, such as warfarin, caution should be exercised and
anticoagulant effect should be monitored.

4.6 Use in Special Populations

Fertility

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

Pregnancy

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

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Topical administration of corticosteroids to pregnant animals can cause abnormalities of foetal
development. (see 6. Nonclinical Properties). The relevance of this finding to humans has not
been established.

In animals miconazole nitrate has shown no teratogenic effects but is fetotoxic at high oral
doses. Only small amounts of miconazole nitrate are absorbed following topical administration.

Therefore, administration of EUMOSONE M 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.

Lactation

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.

Topically applied miconazole is minimally absorbed into the systemic circulation, and it is not
known whether miconazole is excreted in human breast milk.

Administration of EUMOSONE M during lactation should only be considered if the expected

benefit to the mother outweighs the risk to the infant.

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

4.7 Effects on Ability to Drive and Use Machines

There have been no studies to investigate the effect of EUMOSONE M 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 the active ingredients of EUMOSONE M.

4.8 Undesirable Effects

In absence of availability of adverse event data on the fixed dose combination of clobetasone
butyrate and miconazole nitrate, adverse event data of the individual ingredients is presented
below.

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.

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Clobetasone butyrate

Post-marketing Data

Infections and Infestations

Very rare Opportunistic infection

Immune System Disorders

Very rare Hypersensitivity

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

Skin and Subcutaneous Tissue Disorders

Very rare Allergic contact dermatitis, urticaria, skin atrophy*, pigmentation changes*,
exacerbation of underlying symptoms, local skin burning, hypertrichosis, rash,
pruritus, erythema

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

(HPA) axis suppression.

Miconazole nitrate

Adverse reactions reported among 426 patients who received miconazole 2% cream base in 21
double-blind clinical trials are presented in Table 1 below.

Based on pooled safety data from these clinical trials, the most commonly reported adverse
reaction was Application site irritation (0.7%).

Including the above-mentioned adverse reaction, Table 1 displays adverse reactions that have
been reported with the use of topical, non-gynaecological, miconazole nitrate/miconazole from
either clinical trial or postmarketing experiences.

The displayed frequency categories use the following convention: 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);
and very rare (< 1/10,000, including isolated reports) and Not Known (cannot be estimated
from the available data).

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Table 1: Adverse Reactions Reported in Clinical Trials and Post-marketing Experience

System Organ Class Adverse Drug Reactions

Frequency Category
Uncommon Not Known
(≥1/1,000 to <1/100)
Immune System Anaphylactic reaction,
Disorders Hypersensitivity
Skin and Subcutaneous Angioedema
Tissue Disorders Urticaria
Skin burning sensation Contact dermatitis
Skin inflammation Rash
Erythema
Pruritus
General Disorders and Application site reactions
Administration Site (including application site
Conditions irritation, burning, pruritus,
reaction NOS and warmth)

4.9 Overdose

Symptoms and signs

Topically applied clobetasone butyrate 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 4.8 Undesirable Effects).

Excessive use can result in skin irritation, which usually disappears after discontinuation of
therapy. In case of accidental ingestion, stomach irritation may occur.

Treatment

In the event of overdose, EUMOSONE M should be withdrawn gradually by reducing the

frequency of application or by substituting a less potent corticosteroid because of the risk of
glucocorticosteroid insufficiency.

EUMOSONE M is intended for cutaneous use, not for oral use. If accidental ingestion of large
quantities of the product occurs, use appropriate supportive care.

Further management should be as clinically indicated or as recommended by the national

poisons centre, where available.

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5. PHARMACOLOGICAL PROPERTIES

5.1 Mechanism of Action and Pharmacodynamic Properties

Clobetasone butyrate

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

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.

Miconazole nitrate

Miconazole nitrate is an imidazole antifungal agent and may act by interfering with the
permeability of the fungal cell membrane. It possesses a wide antifungal spectrum and has
some antibacterial activity.

5.2 Pharmacokinetic Properties

Clobetasone butyrate

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.

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.

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Miconazole nitrate

Absorption

There is little absorption through skin or mucous membranes when miconazole nitrate is
applied topically.

Distribution

Absorbed miconazole is bound to plasma proteins (88.2%) and red blood cells (10.6%).

Elimination

The small amount of miconazole that is absorbed is eliminated predominantly in faeces as both
unchanged drug and metabolites.

6. NONCLINICAL PROPERTIES

6.1 Animal Toxicology and Pharmacology

Clobetasone butyrate

Carcinogenesis

Long-term animal studies have not been performed to evaluate the carcinogenic potential of
topical clobetasone.

Genotoxicity

Clobetasone was not mutagenic in vitro or in vivo.

Fertility

The effect on fertility of topical clobetasone has not been evaluated in animals.

Pregnancy

Topical application of clobetasone to rats at doses of 0.5 or 5 mg/kg/day, and subcutaneous

administration to mice at doses ≥3 mg/kg/day or rabbits at doses ≥30 µgs/kg/day during
pregnancy resulted in foetal abnormalities including cleft palate.

Miconazole nitrate

Preclinical data reveal no special hazard for humans based on conventional studies of local
irritation, single and repeated dose toxicity, genotoxicity and toxicity to reproduction.

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7. DESCRIPTION

Cream

Contains:

Clobetasone Butyrate IP 0.05 % w/w

Miconazole Nitrate IP 2.0 % w/w
Chlorocresol IP (As Preservative) 0.1 % w/w
in a non-greasy base

List of Excipients

Cetostearyl Alcohol, White Bees Wax, Arlacel 165, Dimethicone 20, Glycerin, Chlorocresol,
Sodium Citrate, Citric acid Monohydrate, Finester 1240, Purified Water.

8. PHARMACEUTICAL PARTICULARS

8.1 Incompatibilities

There are no relevant data available.

8.2 Shelf Life

The expiry date is indicated on the label and packaging.

8.3 Packaging Information

Tube in a carton.

8.4 Storage and Handling Instructions

For external use only.

Store at a temperature not exceeding 30°C. Do not freeze.

Keep out of reach of children.

9. PATIENT COUNSELLING INFORMATION

Registered Medical Practitioners may counsel their patients (and/or their patients’ caregiver as
applicable) about the special warnings and precautions for use, drug interactions, undesirable
effects, and any relevant contraindications of EUMOSONE M. Patients (and/or the patients’
caregiver) may also be informed about posology, method of administration and
storage/handling information as applicable.

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10. DETAILS OF MANUFACTURER

The Manufacturing Site details are mentioned on the label and packaging.

For further information please contact:

GlaxoSmithKline Pharmaceuticals Limited.
Registered Office:
Dr. Annie Besant Road, Worli
Mumbai 400 030, India.

11. DETAILS OF PERMISSION OR LICENCE NUMBER WITH DATE

Manufacturing License number is indicated on the label and packaging.

12. DATE OF REVISION

03-JUN-2024

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

Version: EUM-M/PI/IN/2024/01

Adapted from:
• Clobetasone 17-butyrate (topical) GDS v11 dated 19 May 2020
• Daktarin 2% w/w cream SmPC (last updated on emc: 26 Apr 2023). Available at:
https://www.medicines.org.uk/emc/product/14745/smpc
• Trimovate Cream SmPC (last updated on emc: 26 Feb 2024) Available at:
https://www.medicines.org.uk/emc/product/14458

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