Formoterol + Tiotropium

Usage

Formoterol + Tiotropium is prescribed for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with Chronic Obstructive Pulmonary Disease (COPD), including chronic bronchitis and emphysema. It is also indicated for the long-term maintenance treatment of asthma in patients 6 years and older.

It’s pharmacological classification is bronchodilator (specifically, a combination of a long-acting beta2-adrenergic agonist and a long-acting muscarinic antagonist).

The mechanism of action involves relaxing the muscles in the airways. Formoterol stimulates beta2-adrenergic receptors leading to bronchodilation, while Tiotropium blocks muscarinic cholinergic receptors, further enhancing bronchodilation and reducing mucus secretion.

Alternate Names

There isn’t a single international non-proprietary name for the combination. It is often referred to by the generic names of its components.

Brand names include Tiovair-F, and Stiolto Respimat (containing tiotropium and olodaterol, a similar LABA).

How It Works

Pharmacodynamics: Formoterol, a LABA, stimulates beta2-adrenergic receptors in the lungs, activating adenylate cyclase and increasing intracellular cyclic AMP. This leads to bronchial smooth muscle relaxation. Tiotropium, a LAMA, competitively and reversibly inhibits muscarinic (M1, M2, and M3) receptors, reducing bronchoconstriction and mucus secretion. The combined effect produces sustained bronchodilation.

Pharmacokinetics:

• Formoterol: Rapidly absorbed after inhalation, with peak plasma concentrations reached within 5-10 minutes. Metabolized primarily by direct glucuronidation and eliminated via renal excretion.
• Tiotropium: Absorbed partially from the lungs after inhalation. Systemic bioavailability is low (around 20-30%). Primarily excreted unchanged in the urine, with a terminal elimination half-life of 25-45 hours in COPD patients and 34-44 hours in asthma patients.

Mode of Action: At the cellular level, Formoterol acts on beta2-adrenergic receptors, leading to smooth muscle relaxation via a cAMP-mediated pathway. Tiotropium blocks the effect of acetylcholine at muscarinic receptors, preventing bronchoconstriction.

Dosage

Standard Dosage

Adults (COPD): One inhalation (containing 5 mcg tiotropium and 5 mcg olodaterol, or 18 mcg tiotropium and 12 mcg formoterol dry powder capsule) once daily using the appropriate inhaler device (e.g. Respimat or HandiHaler).

Adults (Asthma): One inhalation (containing 2.5 mcg tiotropium and 2.5 mcg formoterol) once daily.

Children (Asthma): For ages 6 years and older: 2.5 mcg tiotropium and 2.5 mcg formoterol via inhalation once daily. Safety and efficacy have not been established for children under 6.

Special Cases:

• Elderly Patients: No dosage adjustment is typically required. However, monitor closely for adverse effects.
• Patients with Renal Impairment: Caution is advised in moderate to severe renal impairment. Monitor closely.
• Patients with Hepatic Dysfunction: No dosage adjustment is typically required. However, monitor closely.
• Patients with Comorbid Conditions: Use with caution in patients with cardiovascular disease, diabetes, narrow-angle glaucoma, prostatic hyperplasia, bladder-neck obstruction, hyperthyroidism, or seizure disorders.

Clinical Use Cases

Formoterol + Tiotropium is not indicated for acute bronchospasm or emergency situations like intubation, surgical procedures, mechanical ventilation, ICU use, or cardiac arrest. It is for maintenance treatment.

Side Effects

Common Side Effects:

Dry mouth, cough, nasopharyngitis, headache, dizziness, sore throat, hoarseness, upper respiratory tract infection, urinary tract infection, gastrointestinal upset.

Rare but Serious Side Effects:

Paradoxical bronchospasm, angioedema, narrow-angle glaucoma, urinary retention, hypokalemia, hyperglycemia, cardiac arrhythmias (palpitations, tachycardia), allergic reactions.

Contraindications

Hypersensitivity to tiotropium, formoterol, atropine, or its derivatives. Narrow-angle glaucoma.

Drug Interactions

• Beta-blockers: Can antagonize the bronchodilatory effects of formoterol.
• Other Anticholinergics: May increase anticholinergic side effects (e.g., dry mouth, constipation, urinary retention).
• Diuretics: May lead to hypokalemia, increasing the risk of cardiac arrhythmias with formoterol.
• MAO inhibitors: May potentiate the cardiovascular effects of formoterol.
• Tricyclic antidepressants: May enhance the cardiovascular effects of formoterol.

Pregnancy and Breastfeeding

Pregnancy: Limited data available. Generally avoided unless the benefits outweigh the risks.

Breastfeeding: It is unknown if tiotropium/formoterol is excreted in human milk. Caution is advised.

Drug Profile Summary

• Mechanism of Action: Bronchodilation through beta2-adrenergic agonism (formoterol) and muscarinic antagonism (tiotropium).
• Side Effects: Dry mouth, cough, nasopharyngitis, headache, dizziness, paradoxical bronchospasm, angioedema, hypokalemia, hyperglycemia.
• Contraindications: Hypersensitivity, narrow-angle glaucoma.
• Drug Interactions: Beta-blockers, other anticholinergics, diuretics.
• Pregnancy & Breastfeeding: Limited data. Use with caution.
• Dosage: One inhalation daily (specific doses depend on age, indication, and formulation).
• Monitoring Parameters: Lung function (FEV1, FVC), blood glucose (in diabetics), serum potassium.

Popular Combinations

Formoterol + Tiotropium is itself a popular combination. Sometimes, inhaled corticosteroids (ICS) are added to this combination in severe COPD or asthma.

Precautions

• General Precautions: Monitor for paradoxical bronchospasm, cardiac effects, and eye problems (narrow-angle glaucoma). Patients should be trained on proper inhaler technique.
• Specific Populations:
  • Pregnant Women: Discuss risks and benefits with the physician.
  • Breastfeeding Mothers: Potential for neonatal exposure; discuss risks and benefits with the physician.
  • Children & Elderly: Monitor closely for adverse effects.

FAQs (Frequently Asked Questions)

Q1: What is the recommended dosage for Formoterol + Tiotropium in adults with COPD?

A: One inhalation containing 5 mcg tiotropium and 5 mcg olodaterol, or 1 dry powder capsule containing 18 mcg tiotropium and 12 mcg formoterol, once daily.

Q2: What is the recommended dosage for Formoterol + Tiotropium in adults with asthma?

A: One inhalation containing 2.5 mcg of each drug once daily.

Q3: Can Formoterol + Tiotropium be used as a rescue inhaler?

A: No, this medication is not for acute relief of bronchospasm. It’s for long-term maintenance treatment.

Q4: What are the common side effects of Formoterol + Tiotropium?

A: Dry mouth, cough, headache, dizziness, sore throat, nasopharyngitis.

Q5: Are there any contraindications for using Formoterol + Tiotropium?

A: Yes, contraindications include hypersensitivity to the components and narrow-angle glaucoma.

Q6: Can Formoterol + Tiotropium be used during pregnancy or breastfeeding?

A: Limited data is available. Use with caution only if the benefits clearly outweigh the risks. Consult with a specialist.

Q7: What are the potential drug interactions with Formoterol + Tiotropium?

A: Beta-blockers, other anticholinergics, diuretics, and certain antidepressants can interact with Formoterol + Tiotropium.

Q8: How should I counsel patients about using Formoterol + Tiotropium?

A: Emphasize that it’s for maintenance treatment, not for acute relief. Explain proper inhaler technique, potential side effects, and when to seek medical attention. Advise patients to report any eye problems, palpitations, or worsening of respiratory symptoms. Encourage regular follow-up to monitor lung function and adjust therapy as needed.

Q9: What should I monitor in patients taking Formoterol + Tiotropium?

A: Monitor lung function (FEV1, FVC), blood glucose (especially in diabetic patients), serum potassium levels, and cardiovascular parameters like heart rate and blood pressure. Monitor closely for adverse events like paradoxical bronchospasm and signs of narrow-angle glaucoma.