LOCASALEN COMBINATION PRODUCT OINTMENT

Indications

• Allergic conditions
• Dermatitis
• Psoriasis
• Eczema
• Inflammatory skin disorders
• Certain autoimmune diseases
• Asthma exacerbations

Dosage

Adults: Refer to BNF for specific dosing guidance based on the condition being treated. Typically, dosages may vary

Mechanism of action

Flumethasone functions as a glucocorticoid receptor agonist. Upon binding to the glucocorticoid receptor, the receptor-ligand complex translocates to the nucleus, where it influences gene expression. The anti-inflammatory effects are mediated through the induction of lipocortins, which inhibit phospholipase A2, thereby reducing the release of arachidonic acid and subsequently decreasing the production of inflammatory mediators such as prostaglandins and leukotrienes. Additionally, flumethasone suppresses immune system activity by lowering lymphocyte function, decreasing immunoglobulin and complement levels, and impairing antigen-antibody interactions.

Pharmacodynamics

Flumethasone pivalate, being a moderately potent corticosteroid ester, exhibits concentrated anti-inflammatory effects at the application site due to its privalate salt form. This leads to effective and rapid relief from inflammation, exudation, and pruritus. Its pharmacodynamic profile allows for targeted treatment of localized inflammatory conditions, resulting in improved patient outcomes.

Pharmacokinetics

Flumethasone is absorbed following topical application, with its effects being localized due to its ester form. It is bound in circulation primarily to plasma transcortin, but becomes active when unbound. The distribution, metabolism, and excretion details specific to flumethasone are not extensively documented, but general corticosteroid pharmacokinetics suggest hepatic metabolism and renal excretion as key processes in its clearance from the body.

Contra-indications

• Systemic fungal infections
• Hypersensitivity to flumethasone or any of its components
• Active untreated infections
• Peptic ulcer disease

Adverse effects

• Weight gain
• Hypertension
• Hyperglycemia
• Osteoporosis
• Adrenal suppression
• Cushing's syndrome
• Mood changes
• Increased susceptibility to infections

Interactions

• Non-steroidal anti-inflammatory drugs (NSAIDs) may increase gastrointestinal side effects
• Anticoagulants may have altered effects
• Live vaccines may be less effective in patients receiving corticosteroids

Precautions

• Use with caution in patients with a history of tuberculosis
• Monitor for signs of infection
• Long-term use may require tapering to avoid adrenal insufficiency
• Caution in patients with diabetes or hypertension

Pregnancy

Flumethasone should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is categorized as a Category C drug.

Breast-feeding

Caution is advised when administering flumethasone to breastfeeding mothers as it is excreted in breast milk.

Storage

Store in a cool, dry place away from direct sunlight. Keep out of reach of children.

Formulations

• Topical cream
• Topical ointment
• Injectable solution

Indications

• Acne vulgaris
• Psoriasis
• Warts
• Seborrheic dermatitis
• Dandruff
• Hyperkeratosis

Dosage

Adults: For topical application, salicylic acid is typically applied once or twice daily, depending on the formulation and condition being treated. Specific dosing guidelines should be followed as per the BNF.

Mechanism of action

Salicylic acid exerts its effects by penetrating the skin and exfoliating the stratum corneum through keratolytic action, which helps in the dissolution of keratin and the removal of dead skin cells. This action facilitates the clearance of pores and can reduce acne lesions. Additionally, salicylic acid has anti-inflammatory properties that can help to decrease swelling and redness associated with various skin conditions. The compound is also known to inhibit the activity of enzymes involved in the synthesis of prostaglandins, which are mediators of inflammation.

Pharmacodynamics

The pharmacodynamics of salicylic acid involve its ability to enhance the turnover of skin cells and reduce the cohesiveness of keratinocytes in the stratum corneum. This leads to increased desquamation and a reduction in the formation of microcomedones in acne. Its anti-inflammatory effects are mediated through the inhibition of cyclooxygenase enzymes, leading to decreased production of pro-inflammatory mediators. This contributes to the reduction of inflammation and pain in affected areas.

Pharmacokinetics

Salicylic acid is absorbed percutaneously when applied topically, with systemic absorption increasing with higher concentrations and prolonged application. Once absorbed, it is metabolized predominantly in the liver to various conjugates, which are then excreted by the kidneys. The elimination half-life can vary based on the formulation and concentration used. For topical applications, significant first-pass metabolism may occur, limiting systemic exposure and reducing potential systemic side effects.

Pregnancy

Salicylic acid is classified as pregnancy category C. Its use should be avoided during pregnancy unless the potential benefits outweigh the risks.

Breast-feeding

Salicylic acid is excreted in breast milk, and caution is advised when using it during breastfeeding.

Storage

Store in a cool, dry place away from direct light.

Mechanism of action

Flumethasone is a glucocorticoid receptor agonist. This complex binds to the nucleus causing a variety of genetic activation and repressions. The antiinflammatory actions of corticosteroids are thought to involve lipocortins, phospholipase A2 inhibitory proteins which, through inhibition arachidonic acid, control the biosynthesis of prostaglandins and leukotrienes. The immune system is suppressed by corticosteroids due to a decrease in the function of the lymphatic system, a reduction in immunoglobulin and complement concentrations, the precipitation of lymphocytopenia, and interference with antigen-antibody binding. Flumethasone binds to plasma transcortin, and it becomes active when it is not bound to transcortin.

Pharmacodynamics

Flumethasone pivalate is a moderately potent difluorinated corticosteroid ester with anti-inflammatory, antipruritic and vasoconstrictive properties. As it is a privalate salt, its anti-inflammatory action is concentrated at the site of application. This local effect on diseased areas results in a prompt decrease in inflammation, exudation and itching.