SALMETEROL-FLUTICASONE-25+125 (25 + 125)MCG PRESSURISED INHALATION

Indications

• Asthma
• Chronic obstructive pulmonary disease (COPD)

Dosage

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

Adults: Refer to the BNF for specific dosing guidelines.

Mechanism of action

Salmeterol acts on beta-2 adrenergic receptors in the bronchial smooth muscle, leading to relaxation and bronchodilation. Fluticasone exerts its anti-inflammatory effects by binding to glucocorticoid receptors in the cytoplasm of target cells, resulting in the regulation of gene expression and the inhibition of pro-inflammatory cytokine production. This dual action helps to alleviate symptoms and reduce the frequency of exacerbations in respiratory conditions.

Pharmacodynamics

The bronchodilator effect of salmeterol begins within 30 minutes of administration, with peak effects occurring within 3 to 4 hours and lasting for up to 12 hours. Fluticasone's anti-inflammatory effects may take several hours to manifest, with maximum benefit typically observed after consistent use over several days. The combination improves lung function, reduces airway hyperresponsiveness, and enhances overall respiratory health.

Pharmacokinetics

Salmeterol is absorbed systemically, with a bioavailability of approximately 27% due to extensive first-pass metabolism. It has a half-life of around 5 hours. Fluticasone has a high first-pass effect, resulting in a low systemic bioavailability of about 1%. Its half-life is approximately 8 hours. Both drugs are metabolized in the liver, primarily via cytochrome P450 enzymes, and are excreted primarily in feces and urine.

Contra-indications

• Hypersensitivity to salmeterol, fluticasone, or any of the excipients
• Severe asthma exacerbations
• Acute respiratory failure

Adverse effects

• Headache
• Dizziness
• Palpitations
• Tremor
• Muscle cramps
• Throat irritation
• Oral candidiasis
• Cough
• Nausea
• Hypertension

Interactions

• Beta-blockers may reduce the effectiveness of salmeterol
• Concomitant use with other sympathomimetics may increase the risk of cardiovascular side effects
• CYP3A4 inhibitors may increase plasma concentrations of fluticasone, leading to increased side effects

Precautions

• Use with caution in patients with cardiovascular disorders
• Monitor for paradoxical bronchospasm
• Assess adrenal function in patients on long-term therapy
• Consider potential for immunosuppression with prolonged use

Pregnancy

There are no adequate and well-controlled studies in pregnant women. Use only if the potential benefit justifies the potential risk to the fetus.

Breast-feeding

Fluticasone and salmeterol are excreted in breast milk. Caution should be exercised when administering to nursing mothers.

Storage

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

Formulations

• Inhaler
• Dry powder inhaler
• Metered-dose inhaler