FLUSAL 125 HFA 125/25mcg INHALER

Indications

• Reversible airways obstruction in patients requiring long-term regular bronchodilator therapy
• Nocturnal asthma
• Chronic asthma in patients who regularly use an inhaled corticosteroid
• Prevention of exercise-induced bronchospasm

Dosage

Children: For children aged 5-11 years, the recommended dose is 50 micrograms twice daily. In

Adults: The typical adult dose is 50 micrograms twice daily, with the possibility of increasing to 100 micrograms twice daily in cases of more severe airway obstruction.

Mechanism of action

Salmeterol exerts its effects through stimulation of beta-2 adrenoceptors, causing relaxation of bronchial smooth muscle and bronchodilation. It binds to both the active site and an exo-site of the beta-2 adrenoceptor. The saligenin moiety attaches to the active site, while the hydrophilic tail interacts with leucine residues in the exo-site, leading to a prolonged action. Additionally, salmeterol inhibits the release of mast cell mediators and attenuates allergen-induced bronchial hyper-responsiveness.

Pharmacodynamics

As a long-acting beta-2 adrenergic receptor agonist, salmeterol has a longer duration of action compared to short-acting beta agonists like salbutamol. It enhances intracellular cAMP levels, which promotes smooth muscle relaxation. Patients should be aware of potential risks such as hypokalemia and hypoglycemia, and the importance of not using it as monotherapy for asthma management.

Pharmacokinetics

Salmeterol is administered via inhalation, with an onset of action within 15 minutes and a duration of effect lasting approximately 12 hours at recommended doses. It undergoes hepatic metabolism and is eliminated primarily via the feces. The pharmacokinetic profile allows for twice-daily dosing to maintain therapeutic effects.

Adverse effects

• Tachycardia
• Palpitations
• Tremors
• Headache
• Dizziness
• Nervousness
• Hypokalemia
• Hyperglycemia

Interactions

• cenobamate+salmeterol: Moderate (decreases exposure)
• cobicistat+salmeterol: Unknown (increases exposure)
• idelalisib+salmeterol: Unknown (increases exposure)

Precautions

• Use with caution in patients with cardiovascular disorders.
• Monitor for signs of hypokalemia, especially if used with diuretics.
• Not to be used as monotherapy for asthma; should be used with an inhaled corticosteroid.

Pregnancy

Salmeterol is classified as category C. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Salmeterol is excreted in breast milk. Use with caution, weighing the benefits against potential risks.

Storage

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

Formulations

• Inhalation powder - Serevent Accuhaler (50 micrograms per dose)
• Pressurised inhalation - Neovent (25 micrograms per dose)
• Pressurised inhalation - Serevent Evohaler (50 micrograms per dose)
• Inhalation powder - Soltel (25 micrograms per dose)

Indications

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Allergic rhinitis
• Nasal polyps
• Skin conditions such as eczema and psoriasis (topical use)

Dosage

Children: Refer to the BNF for Children for specific dosing guidelines.

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Fluticasone propionate exerts its effects by binding to glucocorticoid receptors in target tissues, leading to the regulation of gene expression. This results in the inhibition of inflammatory cytokines and mediators, thereby reducing inflammation and immune response. It also decreases the production of mucus and enhances the responsiveness of beta-adrenergic receptors in the airways.

Pharmacodynamics

The drug demonstrates a high affinity for the glucocorticoid receptor and exhibits potent anti-inflammatory effects. Fluticasone propionate has been shown to reduce airway hyperreactivity and improve pulmonary function in patients with asthma and chronic obstructive pulmonary disease (COPD). Its anti-inflammatory action is dose-dependent, and therapeutic effects can be seen with regular use, although it may take several days to achieve optimal control of symptoms.

Pharmacokinetics

Fluticasone propionate is rapidly absorbed following inhalation, with peak plasma concentrations occurring within a few hours. The drug undergoes extensive first-pass metabolism in the liver, primarily by cytochrome P450 3A4, resulting in a low bioavailability of less than 1% when administered via inhalation. The elimination half-life is approximately 7.8 hours. It is primarily excreted in the feces, with a small percentage eliminated in urine as metabolites.

Contra-indications

• Hypersensitivity to fluticasone propionate or any excipients
• Active or untreated infections
• Severe hypersensitivity reactions

Adverse effects

• Oropharyngeal candidiasis
• Dysphonia
• Cough
• Nasal irritation
• Headache
• Nasal bleeding
• Systemic corticosteroid effects (with high doses or long-term use)

Interactions

• CYP3A4 inhibitors (may increase systemic exposure to fluticasone)
• Ritonavir (increased effects and potential for systemic side effects)
• Other immunosuppressants (may increase risk of infections)

Precautions

• Use with caution in patients with active or latent tuberculosis
• Caution in patients with untreated fungal, bacterial, or viral infections
• Monitor for adrenal suppression in long-term use
• Use cautiously in patients with cardiovascular disorders

Pregnancy

Fluticasone propionate should only be used during pregnancy if the benefits outweigh the risks. Consultation with a healthcare provider is recommended.

Breast-feeding

Fluticasone propionate is excreted in breast milk, caution is advised when administered to nursing mothers.

Storage

Store at room temperature, away from moisture and heat. Protect from light. Do not freeze.

Formulations

• Nasal spray
• Inhaler (metered dose inhaler)
• Topical cream
• Topical ointment

Indications

• Tinea pedis (athlete's foot)
• Tinea corporis (ringworm)
• Tinea cruris (jock itch)
• Candidiasis (fungal infections caused by Candida species)
• Dermatophyte infections

Dosage

Children: Refer to the BNF for Children for appropriate dosing guidance in paediatric patients.

Adults: Refer to specific product guidelines for dosing recommendations, as they may vary based on the formulation and severity of the fungal infection.

Mechanism of action

Xinefoate exerts its effects by inhibiting the synthesis of ergosterol, an essential component of the fungal cell membrane. This disruption in ergosterol production compromises the integrity of the cell membrane, leading to increased permeability and ultimately cell death.

Pharmacodynamics

The pharmacodynamics of xinefoate involve its action on the fungal cell membrane, resulting in the inhibition of fungal growth and replication. It demonstrates fungicidal properties against a range of fungi, making it effective in treating conditions like tinea pedis, tinea corporis, and candidiasis.

Pharmacokinetics

Xinefoate is typically applied topically, leading to localized action with minimal systemic absorption. It is metabolized in the skin and excreted primarily through the skin and urine. The onset of action usually occurs within days of application, depending on the severity of the infection and the formulation used.

Pregnancy

Use in pregnancy should be avoided unless the benefits outweigh the risks, as safety in pregnant women has not been established.

Breast-feeding

Caution is advised when administering to breastfeeding women, as it is not known if xinefoate is excreted in human milk.

Storage

Store at room temperature, away from moisture and heat. Keep out of reach of children.

Mechanism of action

Beta-2 adrenoceptor stimulation causes relaxation of bronchial smooth muscle, bronchodilation, and increased airflow. Salmeterol is hypothesized to bind to 2 sites on the beta-2 adrenoceptor. The saligenin moiety binds to the active site of the beta-2 adrenoceptor. The hydrophilic tail of salmeterol binds to leucine residues in the exo-site of the beta-2 adrenoceptor almost irreversibly, allowing salmeterol to persist in the active site, which is responsible for it's long duration of action. Another hypothesis is that the lipophilic drug diffuses into lipid bilayer of smooth muscle cells and provides a depot of drug to the cells over a longer period of time. In vitro tests show that salmeterol is a potent and long-lasting inhibitor of the release of mast cell mediators, such as histamine, leukotrienes, and prostaglandin D2, from human lung. Salmeterol inhibits histamine-induced plasma protein extravasation and inhibits platelet activating factor-induced eosinophil accumulation in the lungs of guinea pigs when administered by the inhaled route. In humans, single doses of salmeterol attenuate allergen-induced bronchial hyper-responsiveness. The pharmacologic effects of beta2-adrenoceptor agonist drugs, including salmeterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3',5'-adenosine monophosphate (cyclic AMP). Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells. Salmeterol is a long-acting beta-adrenergic agonist. In vitro studies and in vivo pharmacologic studies demonstrate that salmeterol is selective for beta2-adrenoceptors compared with isoproterenol, which has approximately equal agonist activity on beta1- and beta2-adrenoceptors. In vitro studies show salmeterol to be at least 50 times more selective for beta2-adrenoceptors than albuterol. Although beta2-adrenoceptors are the predominant adrenergic receptors in bronchial smooth muscle and beta1-adrenoceptors are the predominant receptors in the heart, there are also beta2-adrenoceptors in the human heart comprising 10% to 50% of the total beta-adrenoceptors. The precise function of these is not yet established, but they raise the possibility that even highly selective beta2-agonists may have cardiac effects. Salmeterol ... membrane binding is non-competitive and dissociation is slow so that its effects last for many hours. Despite this, salmeterol does not accumulate in tissues. Its mechanism of action can be explained by binding to a specific exo-site domain of the beta 2-receptor protein to produce continuous stimulation of the active site of the receptor, which gives salmeterol a profile of pharmacological activity unlike that of other beta 2-agonists. Due to its potent and prolonged activation of beta 2-adrenoceptors in airway smooth muscle cells, endothelial cells, mast cells and epithelial cells, salmeterol induces prolonged bronchodilatation, reduced vascular permeability, inhibition of inflammatory mediators, stimulation of ciliary function and modulation of ion and water transport across the bronchial mucosa.

Pharmacodynamics

Salmeterol is a long acting beta-2 adrenergic receptor agonist that binds to both the active and exo sites of the beta-2 adrenergic receptor. Salmeterol has a longer duration of action than other beta-2 agonists like [salbutamol]. Patients should be counselled regarding the risks of long acting beta agonist (LABA) monotherapy, hypokalemia, hypoglycemia, and not to take this drug with another LABA.