Fluticasone Propionate + Formoterol

Usage

• Medical Conditions: Fluticasone Propionate + Formoterol is prescribed for the regular long-term treatment of asthma in patients 12 years and older and for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adults. It is indicated for patients whose asthma is not adequately controlled with inhaled corticosteroids and “as needed” inhaled short-acting β2-agonists, or for patients already adequately controlled on both an inhaled corticosteroid and a long-acting β2-agonist.
• Pharmacological Classification: This drug is a combination product containing:
  • Fluticasone propionate: Inhaled Corticosteroid (ICS)
  • Formoterol fumarate dihydrate: Long-acting β2-adrenergic agonist (LABA) bronchodilator
• Mechanism of Action: Fluticasone propionate works by reducing inflammation in the airways. Formoterol fumarate relaxes the muscles around the airways, allowing them to open up, thus easing breathing.

Alternate Names

• No widely used alternate names exist for the combined medication itself. The individual components are sometimes referred to as Fluticasone and Formoterol.
• Brand Names: Flutiform, Fluticasone/Formoterol, Fluticasone Propionate/Formoterol Fumarate

How It Works

• Pharmacodynamics: Fluticasone propionate exerts its anti-inflammatory effects by binding to glucocorticoid receptors in the lungs. This leads to the downregulation of inflammatory mediators, thereby reducing airway inflammation and hyperresponsiveness. Formoterol fumarate activates β2-adrenergic receptors in the bronchial smooth muscle, causing relaxation and bronchodilation. It also inhibits the release of inflammatory mediators from mast cells.

• Pharmacokinetics:

  • Absorption: Both drugs are absorbed through the lungs after inhalation.
  • Metabolism: Fluticasone propionate is extensively metabolized in the liver by CYP3A4 enzymes. Formoterol is primarily metabolized by direct glucuronidation and O-demethylation.
  • Elimination: Fluticasone propionate is primarily eliminated in the feces, with a small amount in urine. Formoterol and its metabolites are primarily excreted in the urine.

• Mode of Action: At the cellular level, Fluticasone reduces inflammation by inhibiting inflammatory cell migration and activation. Formoterol relaxes the airways by increasing intracellular cyclic AMP levels, which in turn activates protein kinase A, leading to smooth muscle relaxation.

• Receptor Binding/Enzyme Inhibition: Fluticasone binds to glucocorticoid receptors. Formoterol binds to β2-adrenergic receptors. Fluticasone is metabolized by CYP3A4.

• Elimination Pathways: Fluticasone propionate: Hepatic metabolism (CYP3A4), primarily fecal excretion. Formoterol fumarate: Primarily renal excretion.

Dosage

Standard Dosage

Adults (18 years and older):

• Flutiform 50/5: Two inhalations (puffs) twice daily (morning and evening).
• Flutiform 125/5: Two inhalations twice daily.
• Flutiform 250/10: Two inhalations twice daily. (This is the maximum recommended dose for adults with asthma).

Children (12-17 years):

• Flutiform 50/5: Two inhalations twice daily.
• Flutiform 125/5: Two inhalations twice daily.
• Children under 12 years: Not recommended.

Special Cases:

• Elderly Patients: No specific dose adjustment is necessary.
• Patients with Renal Impairment: No data are available for Flutiform in patients with renal impairment. These patients should be monitored carefully by a physician.
• Patients with Hepatic Dysfunction: Patients with hepatic impairment should be monitored for increased drug exposure.
• Patients with Comorbid Conditions: Caution is advised for patients with cardiovascular diseases, diabetes, seizures, hyperthyroidism, hypokalemia, tuberculosis, infections, and glaucoma. Dosage adjustments may be necessary depending on the specific comorbidity.

Clinical Use Cases

Fluticasone Propionate + Formoterol is not indicated for:

• Intubation
• Surgical Procedures
• Mechanical Ventilation
• Intensive Care Unit (ICU) Use
• Emergency Situations (e.g., status epilepticus, cardiac arrest)

It is for maintenance treatment of asthma and COPD, not acute exacerbations.

Dosage Adjustments

Dose modifications are based on individual patient response and control of asthma or COPD symptoms. Patients should be titrated to the lowest effective dose. Close monitoring of patients with hepatic dysfunction is essential.

Side Effects

Common Side Effects:

Headache, throat irritation, oral candidiasis (thrush), upper respiratory tract infection, cough, hoarseness, dysphonia, tremor.

Rare but Serious Side Effects:

Paradoxical bronchospasm, hypersensitivity reactions (including anaphylaxis), angioedema, hypokalemia, hyperglycemia, pneumonia (in COPD patients), QT prolongation, adrenal suppression, growth retardation in children, cataracts, glaucoma, osteoporosis, immunosuppression.

Long-Term Effects:

Osteoporosis, cataracts, glaucoma, adrenal suppression, growth suppression (in children), increased risk of infections.

Adverse Drug Reactions (ADR):

Severe allergic reactions (anaphylaxis), severe hypokalemia, cardiac arrhythmias, worsening of asthma/COPD, adrenal crisis.

Contraindications

• Hypersensitivity to fluticasone propionate, formoterol fumarate, or any of the excipients.
• Severe milk protein allergy.
• Acute asthma exacerbations.
• Primary treatment of status asthmaticus or other acute episodes of COPD.

Drug Interactions

• Strong CYP3A4 inhibitors (e.g., ketoconazole, ritonavir): Can increase the systemic exposure of fluticasone, increasing the risk of side effects.
• Beta-blockers (e.g., propranolol, metoprolol): Can antagonize the bronchodilating effects of formoterol.
• Diuretics (e.g., furosemide, hydrochlorothiazide): Can potentiate hypokalemia caused by formoterol.
• Tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs): Can enhance the cardiovascular effects of formoterol.
• Xanthine derivatives, other LABAs, and systemic corticosteroids: Can potentiate the effects and side effects of formoterol.

Pregnancy and Breastfeeding

• Pregnancy: Limited data. Not generally recommended unless the potential benefit to the mother outweighs the potential risk to the fetus. Use the lowest effective dose if necessary.

• Breastfeeding: It is unknown if fluticasone propionate or formoterol are excreted in human milk. Weigh the benefits of breastfeeding against the potential risks to the infant.

Drug Profile Summary

• Mechanism of Action: Fluticasone: Anti-inflammatory by binding to glucocorticoid receptors. Formoterol: Bronchodilation by activating β2-adrenergic receptors.

• Side Effects: Common: Headache, throat irritation, candidiasis. Serious: Paradoxical bronchospasm, hypokalemia, hyperglycemia, adrenal suppression.

• Contraindications: Hypersensitivity, acute asthma attack, severe milk protein allergy.

• Drug Interactions: CYP3A4 inhibitors, beta-blockers, diuretics, TCAs, MAOIs.

• Pregnancy & Breastfeeding: Limited data, use with caution if benefits outweigh risks.

• Dosage: Adults: Flutiform 50/5, 125/5 or 250/10 twice daily. Children (12-17): Flutiform 50/5 or 125/5 twice daily. Not recommended for children under 12.

• Monitoring Parameters: Lung function (FEV1, peak flow), serum potassium, blood glucose, bone mineral density (for long-term use), blood pressure, signs of adrenal insufficiency, growth in children.

Popular Combinations

This medication already combines an ICS and a LABA. Combination with other asthma/COPD medications may be used, but careful consideration is required due to potential drug interactions and additive side effects. For example, adding a long-acting muscarinic antagonist (LAMA) may provide additional benefit for some COPD patients.

Precautions

• General Precautions: Evaluate patient’s medical history, including cardiac, hepatic, and renal function, as well as any current medications. Monitor for adverse effects.

• Specific Populations: Caution should be exercised in patients with heart conditions, diabetes, high blood pressure, glaucoma, cataracts, infections, osteoporosis, seizures, hypokalemia, hyperthyroidism, and those at risk for low potassium.

• Lifestyle Considerations: Advise patients to avoid smoking and limit alcohol intake.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Fluticasone Propionate + Formoterol?

A: Adults: Flutiform 50/5, 125/5, or 250/10 mcg twice daily. Adolescents (12-17 years): Flutiform 50/5 or 125/5 mcg twice daily. Not for children under 12.

Q2: How should this medication be administered?

A: Via oral inhalation using a metered-dose inhaler (MDI). Patients should be instructed on the correct inhaler technique.

Q3: Can this drug be used during pregnancy?

A: It should only be used if the benefits outweigh the risks.

Q4: Can I take this medicine with food?

A: It can be taken with or without food.

Q5: What should be done if a dose is missed?

A: Take the missed dose as soon as remembered, unless it is close to the next scheduled dose. Never double the dose.

Q6: What are the common side effects?

A: Headache, throat irritation, and oral candidiasis.

Q7: What are the serious side effects?

A: Paradoxical bronchospasm, allergic reactions, hypokalemia, hyperglycemia.

Q8: How long does it take for Fluticasone Propionate + Formoterol to work?

A: Formoterol provides rapid bronchodilation within minutes, but the full benefits of the combined medication for asthma and COPD control may take several days or weeks of regular use to become apparent.

Q9: Can this drug cure asthma or COPD?

A: No. It is a maintenance medication to control symptoms and prevent exacerbations, but it does not cure the underlying disease.

Q10: Is it safe to use this medicine daily for a long time?

A: Yes, it is intended for daily long-term use as prescribed by a physician. Regular monitoring is essential.