Fluticasone propionate (micronized) 0.05% w/w (500 micrograms/g). It also contains Imidurea 0.2% w/w as a preservative.
Excipients/Inactive Ingredients: Liquid paraffin, Cetostearyl alcohol, Isopropyl myristate, Cetomacrogol 1000, Propylene glycol, Imidurea, Sodium phosphate, Citric acid monohydrate, Purified water.
Pharmacotherapeutic Group: Corticosteroid, potent (Group III). ATC Code: D07AC.
Pharmacology: Pharmacodynamics: 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.
Pharmacokinetics: 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 CUTIVATE Cream will be low.
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.
Toxicology: Pre-Clinical 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.
Treatment of Inflammatory Dermatoses: CUTIVATE Cream is indicated for adults and children aged 1 year and over for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses such as: Eczema including atopic, infantile, and discoid eczemas; Prurigo nodularis; Psoriasis (excluding widespread plaque psoriasis); Neurodermatoses including lichen simplex; Lichen planus; Seborrhoeic dermatitis; Contact sensitivity reactions; Discoid lupus erythematosus; An adjunct to systemic steroid therapy in generalised erythroderma; Insect bite reactions; Prickly heat.
CUTIVATE Cream is indicated for children aged 3 months to less than 1 year for the relief of the inflammatory and pruritic manifestations of corticosteroid-responsive dermatoses such as: Eczema including atopic, infantile, and discoid eczemas; Prurigo nodularis; Psoriasis (excluding widespread plaque psoriasis); Neurodermatoses including lichen simplex; Lichen planus; Seborrhoeic dermatitis; Contact sensitivity reactions; Discoid lupus erythematosus; An adjunct to systemic steroid therapy in generalised erythroderma.
The safety and efficacy of drug use for longer than 4 weeks in this population have not been established. The safety and efficacy of CUTIVATE Cream in paediatric patients below 3 months of age have not been established.
Reduction of Risk of Relapse: CUTIVATE Cream is indicated for the reduction of the risk of relapse of chronic recurrent atopic eczema once an acute episode has been treated effectively.
Adults, elderly, children and infants aged 3 months and over: Creams are especially appropriate for moist or weeping surfaces.
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.
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 CUTIVATE 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 toxicity. Therefore the minimum quantity should be used for the shortest duration to achieve the desired clinical benefit.
Symptoms and Signs: Topically applied fluticasone propionate may be absorbed in sufficient amounts to product 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 Adverse Reactions).
Treatment: In the event of overdose, CUTIVATE 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.
The following conditions should not be treated with CUTIVATE 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.
CUTIVATE 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 Adverse Reactions) may resemble symptoms of the condition under treatment.
Manifestations of hypercortisolism (Cushing's Syndrome) and reversible hypothalamic-pituitary-adrenal (HPA) axis suppression, leading to a glucocorticosteroid insufficiency, can occur in some individuals as a result of increased systemic absorption of topical steroids. If either of the previously mentioned 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 Adverse Reactions).
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.
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 undersirable 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 antimicrobial therapy.
Infection risk with occlusion: Bacterial infection is encouraged by the warm, moist conditions within skin folds or caused by occlusive dressing. When using occlusive dressing, 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.
Overt suppression of the HPA-axis (morning plasma cortisol less than 5 micrograms/dL) is very unlikely to result from therapeutic use of CUTIVATE Cream unless treating more than 50% of an adult's body surface and applying more than 20 g per day.
CUTIVATE Cream contains the excipient imidurea which releases traces of formaldehyde as a breakdown product. Formaldehyde may cause allergic sensitisation or irritation upon contact with the skin.
Effects on Ability to Drive and Use Machines: There have been no studies to investigate the effect of CUTIVATE 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 CUTIVATE Cream.
Use in 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.
Fertility: There are no data in humans to evaluate the effect of topical corticosteroids on fertility (see Pharmacology: Toxicology: Pre-Clinical Safety Data under Actions).
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 Pharmacology: Toxicology: Pre-Clinical Safety Data under Actions). The relevance of this finding to humans has not been established; however, administration of CUTIVATE 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 product 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 CUTIVATE Cream during lactation should only be considered if the expected benefit to the mother outweighs the risk to the infant.
If used during lactation, CUTIVATE Cream should not be applied to the breasts to avoid accidental ingestion by the infant.
Adverse drug reactions (ADRs) are listed as follows 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.
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: Pruritus. Uncommon: Local skin burning. Very rare: Skin thinning, atrophy, striae, telangiectasias, pigmentation changes, hypertrichosis, allergic contact dermatitis, exacerbation of underlying symptoms, pustular psoriasis, erythema, rash, urticaria.
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.
Instructions for Use/Handling: There are no special requirements for use or handling of this product.
Incompatibilities: No incompatibilities have been identified.
Store below 30°C.
Do not freeze.
D07AC17 - fluticasone ; Belongs to the class of potent (group III) corticosteroids. Used in the treatment of dermatological diseases.