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

FLUTIVATE E CREAM

Fluticasone Cream I.P.

QUALITATIVE AND QUANTITATIVE COMPOSITION

FLUTIVATE E CREAM contains:

Fluticasone Propionate I.P. 0.05 %w/w
Preservatives:
Methylparaben I.P. 0.17 % w/w
Propylparaben I.P. 0.06% w/w
Imidurea I.P. 0.14% w/w

PHARMACEUTICAL FORM

Cream - “Oil- in- Water” type of emulsion (Hydrophilic Cream).

CLINICAL PARTICULARS

Therapeutic Indications

Treatment of Inflammatory Dermatoses

FLUTIVATE E CREAM is a potent topical corticosteroid indicated for adults, children and
infants aged 3 months and over for the relief of the inflammatory and pruritic manifestations
of corticosteroid-responsive dermatoses.

These include the following:

• Atopic dermatitis (including infantile atopic dermatitis)

• Nummular dermatitis (discoid eczemas)
• Prurigo nodularis
• Psoriasis (excluding widespread plaque psoriasis)
• Lichen simplex chronicus (neurodermatitis) and lichen planus
• Seborrhoeic dermatitis
• Irritant or allergic contact dermatitis
• Discoid lupus erythematosus
• An adjunct to systemic steroid therapy in generalized erythroderma
• Insect bite reactions
• Miliaria (prickly heat)

Reduction of risk of relapse

FLUTIVATE E CREAM is indicated for the reduction of the risk of relapse of chronic recurrent
atopic dermatitis once an acute episode has been treated effectively.

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Posology and Method of Administration

Adults, elderly, children and infants aged 3 months and over

Hydrophilic Creams (having thin consistency) are especially appropriate for treatment of hairy
areas or when a minimal application to a large area is required.

Treatment of Inflammatory Dermatoses

Apply thinly and gently rub in using only enough to cover the entire affected area once or twice
a day for up to 4 weeks until improvement occurs, 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. If the condition worsens or does not improve
within 2 to 4 weeks, treatment and diagnosis should be re-evaluated.

Atopic Dermatitis

Therapy with topical corticosteroids 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 topical steroids
especially with potent preparations.

Reduction of Risk of Relapse

Once an acute episode has been treated effectively, application frequency should be reduced to
once daily application, twice weekly, without occlusion. Application should be continued to
all previously affected sites or to known sites of potential relapse. This regime should be
combined with routine daily use of emollients. The condition must be re-evaluated on a regular
basis.

Children over 3 months

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 FLUTIVATE E CREAM to ensure the amount applied is the
minimum that provides therapeutic benefit.

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

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toxicity. Therefore, the minimum quantity should be used for the shortest duration to achieve
the desired clinical benefit.

Contraindications

The following conditions should not be treated with FLUTIVATE E CREAM:

• Untreated cutaneous infections

• Rosacea
• Acne vulgaris
• Perioral dermatitis
• Perianal and genital pruritus
• Pruritus without inflammation
• Dermatoses in infants under 3 months of age, including dermatitis and nappy rash

Special Warnings and Special Precautions for Use

FLUTIVATE E CREAM should be used with caution in patients with a history of local
hypersensitivity to corticosteroids or to any of the excipients in the preparation. Local
hypersensitivity reactions (see Undesirable Effects) 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 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.

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Visual disturbances

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.

Use in psoriasis

Topical steroids should be used with caution in psoriasis as rebound relapses, development of
tolerance, 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.

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 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.

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.

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.

FLUTIVATE E CREAM contains the excipient imidurea which releases traces of formaldehyde
as a breakdown product.

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Formaldehyde may cause allergic sensitization or irritation upon contact with the skin.

Interaction with Other Medicaments and Other Forms of Interaction

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.

Pregnancy and Lactation

Fertility

There are no data in humans to evaluate the effect of topical corticosteroids on fertility (see
Preclinical Safety Data).

Pregnancy

There are limited data from the use of fluticasone propionate in pregnant women. Topical
administration of corticosteroids to pregnant animals can cause abnormalities of foetal
development (see Preclinical Safety Data). The relevance of this finding to humans has not
been established; however, administration of FLUTIVATE E CREAM during pregnancy should
only be considered if the expected benefit to the mother is greater than any possible 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.

When measurable plasma levels were obtained in lactating laboratory rats following
subcutaneous administration there was evidence of fluticasone propionate in the milk.

Administration of FLUTIVATE E CREAM during lactation should only be considered if the

expected benefit to the mother outweighs the risk to the infant.

If used during lactation, FLUTIVATE E CREAM should not be applied to the breasts to avoid
accidental ingestion by the infant.

Effects on Ability to Drive and Use Machines

There have been no studies to investigate the effect of FLUTIVATE 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 FLUTIVATE E CREAM.

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Undesirable Effects

Post-Marketing Data

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 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.

Infections and infestations

Very rare: Opportunistic infection.

Immune system disorders

Very rare: Hypersensitivity.

Endocrine disorders

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

• Increased weight/obesity
• Delayed weight gain/growth retardation in children
• Cushingoid features (e.g. moon face, central obesity)
• Decreased endogenous cortisol levels
• Hyperglycaemia/glucosuria
• Hypertension
• Osteoporosis
• Cataract
• Glaucoma

Skin and subcutaneous tissue disorders

Common: Local skin burning.

Uncommon: Pruritus.
Very rare: Skin thinning, atrophy, striae, telangiectasias, pigmentation changes,
hypertrichosis, allergic contact dermatitis, exacerbation of underlying
symptoms, pustular psoriasis, erythema, rash, urticaria.

Overdose

Symptoms and Signs

Topically applied fluticasone propionate 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 appear (see Undesirable Effects).

Treatment

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In the event of overdose, FLUTIVATE E CREAM 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

Pharmacodynamic Properties

Pharmacotherapeutic Group: Corticosteroid, potent (Group III); ATC Code: D07AC.

Mechanism of Action

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

They 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.

Fluticasone propionate is a glucocorticoid with high topical anti-inflammatory potency but low
HPA-axis suppressive activity after dermal administration. It therefore has a therapeutic index
which is greater than most of the commonly available steroids.

It shows high systemic glucocorticoid potency after subcutaneous administration but very weak
oral activity, probably due to metabolic inactivation. In vitro studies show a strong affinity for
and agonist activity at, human glucocorticoid receptors.

Pharmacodynamic Effects

Fluticasone propionate has no unexpected hormonal effects, and no overt, marked effects upon
the central and peripheral nervous systems, the gastrointestinal system, or the cardiovascular
or respiratory systems.

Pharmacokinetic Properties

Absorption

Bioavailability is very low after topical or oral administration, due to limited absorption
through the skin or from the gastrointestinal tract, and because of extensive first pass
metabolism.

Oral bioavailability approaches zero, due to poor absorption and extensive first pass
metabolism. Therefore, systemic exposure of fluticasone propionate from any ingestion of
FLUTIVATE E CREAM will be low.

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Distribution

Distribution studies have shown that only minute traces of orally administered compound reach
the systemic circulation and that any systemically available fluticasone propionate is rapidly
eliminated in the bile and excreted in the faeces.

Fluticasone propionate does not persist in any tissue, and does not bind to melanin.

Metabolism
Pharmacokinetic data for the rat and dog indicate rapid elimination and extensive metabolic
clearance. In man too, metabolic clearance is extensive, and elimination is consequently rapid.
Thus, drug entering the systemic circulation via the skin will be rapidly inactivated. The major
route of metabolism is hydrolysis to a carboxylic acid, which has very weak glucocorticoid or
anti-inflammatory activity.

Elimination

In all test animal species, the route of excretion was independent of the route of administration
of fluticasone propionate. Excretion is predominantly faecal and is essentially complete within
48 hours.

Preclinical Safety Data

Carcinogenesis/Mutagenesis

Carcinogenesis

Long-term topical and oral studies in animals to investigate the carcinogenic potential of
fluticasone propionate did not show any evidence of carcinogenicity.

Genotoxicity

Fluticasone propionate was not shown to be mutagenic in a range of in vitro bacterial and
mammalian cell assays.

Fertility

In a fertility and general reproductive performance study in rats, fluticasone propionate

administered subcutaneously to females at up to 50 micrograms/kg per day and to males up to
100 micrograms/kg per day (later reduced to 50 micrograms/kg per day) had no effect upon
mating performance or fertility.

Pregnancy

Subcutaneous administration of fluticasone propionate to mice (150 micrograms/kg/day), rats

(100 micrograms/kg/day) or rabbits (300 micrograms/kg/day) during pregnancy produced
foetal abnormalities including cleft palate. Oral administration did not produce foetal
abnormalities, consistent with the low bioavailability of fluticasone propionate by the oral
route.

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PHARMACEUTICAL PARTICULARS

List of Excipients

Imidurea, cetostearyl alcohol, citric acid monohydrate, sodium citrate, methylparaben,

propylparaben, propylene glycol, isopropyl myristate, dimethicone 350, cetomacrogol 1000,
purified water.

Incompatibilities

No incompatibilities have been identified.

Shelf Life

The expiry date is indicated on the label and packaging.

Special Precautions for Storage

Store at temperature below 25° C.

Do not freeze.

Keep out of reach of children.

Nature and Specification of Container

Tube in a carton.

Instructions for Use / Handling

For external use only.

There are no other special requirements for use or handling of this product.

For further information please contact:

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

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

Version: FTVE/PI/IN/2018/02 dated 21 November 2018.

Adapted from Fluticasone Propionate GDS14 / IPI04 dated 09 April 2018.