Locoid

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT LOCOID®

Composition:

Active substance: hydrocortisone 17-butyrate;

1 g of cream contains 1 mg of hydrocortisone 17-butyrate;

Excipients: cetyl stearyl alcohol, macrogol cetyl stearyl ether, light mineral oil, white soft paraffin, propyl parahydroxybenzoate (E 216), butyl parahydroxybenzoate, citric acid anhydrous, sodium citrate, purified water.

Pharmaceutical form. Cream.

Main physicochemical characteristics: white-colored cream, easily applied.

Pharmacotherapeutic group. Corticosteroids for dermatological use.

ATC code: D07AB02.

Pharmacological properties.

Pharmacodynamics.

Hydrocortisone-17-butyrate is an active synthetic non-halogenated corticosteroid for topical use. It exerts anti-inflammatory, anti-edematous, and antipruritic effects. Its efficacy is comparable to that of halogenated steroids. Use at recommended doses does not cause suppression of the hypothalamic-pituitary-adrenal system. Although prolonged use of large doses of the drug, especially when using occlusive dressings, may lead to increased cortisol levels in blood plasma, the reactivity of the pituitary-adrenal system remains unaffected, and cortisol production normalizes after discontinuation of the drug.

Pharmacokinetics.

Absorption. After topical application, the active substance accumulates in the epidermis, primarily in the stratum granulosum.

Metabolism. Hydrocortisone-17-butyrate, absorbed through the skin, is metabolized to hydrocortisone and other metabolites directly in the epidermis, and subsequently in the liver.

Excretion. Metabolites and a minor portion of unchanged hydrocortisone-17-butyrate are excreted in urine and feces.

Clinical Characteristics.

Indications.

Conditions that respond to treatment with topical corticosteroids (e.g., eczema, dermatitis, psoriasis). Topical corticosteroids are generally not indicated for the treatment of psoriasis, but may be acceptable except for widespread plaque psoriasis, provided that precautions are observed (see section "Special Warnings and Precautions for Use").

Contraindications.

Except in cases of combined treatment with appropriate chemotherapeutic agents:

• Skin lesions (wounds) caused by bacterial infections (e.g., pyoderma, syphilitic or tuberculous lesions), viral infections (e.g., varicella, herpes simplex, herpes zoster, common warts, flat warts, genital warts, condylomata acuminata, molluscum contagiosum); fungal and yeast infections; parasitic infections (e.g., scabies);
• ulcerative skin lesions;
• corticosteroid-induced adverse reactions (e.g., perioral dermatitis, striae);
• ichthyosis, juvenile plantar dermatosis, acne vulgaris, rosacea, skin fragility, skin atrophy;
• hypersensitivity reactions to any component of the product or to corticosteroids (the latter are rare);
• skin tumors.

Interaction with other medicinal products and other forms of interaction.

Interaction studies have not been performed.

Special precautions for use.

Systemic adverse reactions following topical application of corticosteroids in adults are extremely rare but may be serious, particularly adrenal cortical suppression during prolonged treatment.

Risk of systemic effects is increased in the following cases:

• application over large skin areas, especially when using occlusive dressings or application to skin folds;
• prolonged treatment;
• use in children (due to thinner skin and relatively larger body surface area);
• presence of components or excipients that enhance penetration through the stratum corneum and/or potentiate the effect of the active substance (e.g. propylene glycol).

Risk of local adverse reactions increases with the potency of the drug and duration of treatment. Use with occlusive dressings or application to skin folds further increases this risk. The facial skin, scalp, and genital areas are particularly susceptible to adverse reactions. Inappropriate use, as well as presence of bacterial, parasitic, fungal, or viral infections, may mask and/or exacerbate manifestations of these conditions.

The ointment should not be applied to the eyelids due to the risk of contact with the conjunctiva and increased risk of developing open-angle glaucoma or subcapsular cataract.

Topical corticosteroids may be hazardous in patients with psoriasis for several reasons, including rebound syndrome due to development of tolerance, risk of generalized pustular psoriasis, or local and systemic toxic effects resulting from impaired skin barrier function. Steroids may be used in scalp psoriasis or chronic plaque psoriasis of hands and feet. Careful monitoring of patients is essential.

Children, including infants.

Adverse effects may occur in infants following excessive use. Particular caution should be exercised in dermatoses of infants, especially diaper dermatitis. In such patients, treatment courses should generally not exceed 7 days.

Adrenal suppression (Cushing's syndrome) may develop rapidly in children. Suppression of growth hormone secretion and intracranial hypertension may also occur. Manifestations of intracranial hypertension include bulging fontanelle, headache, and bilateral optic disc swelling. If long-term treatment is required, regular monitoring of the child's height, body weight, and plasma cortisol levels is advisable.

In comparative studies, no significant differences in adrenal cortical function were observed in children treated with Locoid® cream or 1% hydrocortisone at doses of 30–60 grams per week over 4 weeks.

Excipients contained in the medicinal product.

Cetostearyl alcohol may cause local skin reactions (e.g. contact dermatitis).

Propyl- and butylparahydroxybenzoates may cause delayed allergic reactions.

Use during pregnancy or breastfeeding.

Pregnancy. Data on the use of hydrocortisone butyrate in pregnant women are lacking or limited. Animal studies indicate reproductive toxicity of the drug. Corticosteroids cross the placenta. Systemic administration of high doses of corticosteroids has been associated with effects on the fetus or newborn (fetal growth retardation, adrenal cortical suppression).

Despite limited information on the use of corticosteroids in pregnant women, due to their limited systemic absorption, short-term use of weak and moderately potent corticosteroids (class 1 and class 2), such as hydrocortisone, on limited skin areas may be considered. However, the aforementioned effects cannot be excluded with prolonged use or application over large skin areas. Such use should only be considered if clearly indicated.

Breastfeeding. Hydrocortisone butyrate/metabolites are excreted in breast milk. However, when Locoid® is used at therapeutic doses, no effects on breastfed infants are expected. Locoid® may be used in breastfeeding women only for short-term treatment and on small skin areas. For long-term treatment or application over large affected skin areas, breastfeeding should be discontinued.

Ability to influence reaction speed when driving vehicles or operating machinery.

There are no data on the effect of Locoid® cream on the ability to drive vehicles or operate machinery, and such effects are not expected.

Method of Administration and Dosage

For topical use.

Apply a small amount of the preparation in a thin, even layer to affected areas no more than twice daily.

Application under occlusive dressing may be used in the presence of more resistant lesions, such as thickened psoriatic plaques on elbows and knees (with the exception of weeping lesions).

Dosage

The total cumulative dose should not exceed 30–60 g of cream per week.

Adults and elderly patients

Adults and elderly patients should receive the same dosage, as there are no clinical data indicating that elderly patients require a different dosing regimen.

Children

Prolonged treatment should be avoided whenever possible.

Children aged 6 months to 1 year

If possible, the treatment period should not exceed 7 days.

Overdose.

Excessive use under occlusive dressing may lead to suppression of the adrenal glands. There are no specific antidotes or treatment procedures. If any adverse effects occur, treatment should be discontinued and symptomatic therapy initiated.

Side effects.

Uncommon (>1/10000, <1/1000)

Disorders of the skin and subcutaneous tissue:

• dermatitis, eczema, striae, contact dermatitis;
• allergic contact dermatitis, pustular acne;
• skin atrophy, often irreversible, accompanied by epidermal thinning, telangiectasia, purpura, and striae;
• depigmentation, hypertrichosis;
• rosacea-like and perioral dermatitis, with or without skin atrophy;
• rebound effect, which may lead to steroid dependence;
• delayed wound healing;
• skin infection, redness, irritation, burning, rash, itching, dry skin, folliculitis, miliaria, acne, maceration.

Endocrine disorders: adrenocortical suppression, Cushing's syndrome, hyperglycemia, glucosuria, growth retardation, and intracranial hypertension.

Very rare (<1/10000, including isolated reports)

Eye disorders: increased intraocular pressure and risk of cataract development (with repeated exposure of the drug to the conjunctiva).

Immune system disorders: hypersensitivity reactions.

Reporting of suspected adverse reactions

It is important to report suspected adverse reactions after drug registration. This enables ongoing monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals should report any suspected adverse reactions via the national reporting system.

Shelf life. 3 years.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Do not store in the refrigerator.

Keep out of reach and sight of children.

Packaging.

30 g in a tube; 1 tube in a cardboard box.

Prescription status. Prescription only.

Manufacturer.

Temmler Italia S.r.l.

Temmler Italia S.r.l.

Address of the manufacturer and location of its business operations.

Via delle Industrie, 2, 20061, Carugate (MI), Italy.

Via delle Industrie, 2, 20061, Carugate (MI), Italy.