Usage
- Medical Conditions: Glycopyrrolate + Indacaterol is prescribed for the long-term, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema. It is not indicated for the relief of acute bronchospasm or for the treatment of asthma.
- Pharmacological Classification: Bronchodilator combination (Long-acting muscarinic antagonist [LAMA] + Long-acting beta2-agonist [LABA]).
- Mechanism of Action: This combination drug works by relaxing and widening the airways in the lungs. Indacaterol, the LABA component, stimulates beta2-adrenergic receptors in the lungs, leading to smooth muscle relaxation and bronchodilation. Glycopyrrolate, the LAMA component, blocks the action of acetylcholine at muscarinic receptors, further promoting bronchodilation and reducing mucus secretions.
Alternate Names
- International/Regional Variations: Glycopyrronium + Indacaterol (some regions).
- Brand Names: Utibron Neohaler®, Ultibro Breezhaler®, Seebri® Neohaler (glycopyrrolate alone), Sequadra®.
How It Works
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Pharmacodynamics: Indacaterol acts as a long-acting beta2-adrenergic agonist, relaxing bronchial smooth muscle. Glycopyrrolate acts as a long-acting muscarinic antagonist (anticholinergic), inhibiting acetylcholine’s effect on M1, M2, and M3 muscarinic receptors. This leads to reduced bronchoconstriction and mucus secretion.
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Pharmacokinetics:
- Absorption: Indacaterol is rapidly absorbed after inhalation, reaching peak plasma concentration in about 15 minutes. Glycopyrrolate is poorly absorbed systemically after inhalation, with an absolute bioavailability of around 10-25% and peak concentration in approximately 5 minutes. This low systemic absorption limits its systemic anticholinergic effects while still providing bronchodilation.
- Metabolism: Indacaterol is primarily metabolized by CYP3A4. Glycopyrrolate undergoes minimal metabolism.
- Elimination: Indacaterol is mainly eliminated through feces, with a minor renal component. Glycopyrrolate is eliminated primarily unchanged in the urine.
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Mode of Action: Indacaterol binds to beta2-adrenergic receptors, activating intracellular signaling pathways leading to bronchial smooth muscle relaxation. Glycopyrrolate competitively inhibits acetylcholine binding to muscarinic receptors, preventing bronchoconstriction.
Dosage
Standard Dosage
Adults:
- One capsule (27.5 mcg indacaterol/15.6 mcg glycopyrrolate for Utibron Neohaler or 110 mcg indacaterol/50 mcg glycopyrrolate for Ultibro Breezhaler) inhaled twice daily (morning and evening) or one capsule (110/50mcg Ultibro Breezhaler) once daily, using the Neohaler or Breezhaler device, respectively. Do not swallow the capsules.
Children:
- Use is not recommended in pediatric patients. Safety and efficacy have not been established.
Special Cases:
- Elderly Patients: No dosage adjustment is generally required.
- Patients with Renal Impairment: No dosage adjustment is necessary for mild to moderate impairment. Caution is advised in severe renal impairment and end-stage renal disease; the benefit should outweigh the risk.
- Patients with Hepatic Dysfunction: No dosage adjustment is necessary for mild to moderate impairment. Severe hepatic impairment has not been studied.
- Patients with Comorbid Conditions: Close monitoring is recommended for patients with cardiovascular disease, diabetes, hyperthyroidism, narrow-angle glaucoma, prostatic hyperplasia, urinary retention, or seizure disorders.
Clinical Use Cases
- Glycopyrrolate + Indacaterol is not indicated for acute settings like intubation, surgical procedures, mechanical ventilation, ICU use, or emergency situations. It’s solely for the maintenance treatment of COPD.
Dosage Adjustments:
- No dosage adjustment is required for mild to moderate hepatic or renal impairment.
- For severe renal or hepatic impairment, the drug should be used with caution, and the benefits should outweigh the potential risks.
Side Effects
Common Side Effects:
- Upper respiratory tract infection
- Nasopharyngitis (sore throat and runny nose)
- Runny or stuffy nose
- Headache
- Dizziness
- Cough
- Back pain
- Hypertension
- Urinary tract infection
Rare but Serious Side Effects:
- Angioedema
- Hypersensitivity reactions
- Cardiac arrhythmias (e.g., atrial fibrillation, tachycardia)
- Worsening of narrow-angle glaucoma
- Urinary retention
- Hyperglycemia (particularly in patients with diabetes)
- Hypokalemia
- Paradoxical bronchospasm
Long-Term Effects:
- Data on long-term effects beyond one year are limited.
Contraindications
- Hypersensitivity to indacaterol, glycopyrrolate, or any component of the formulation (including milk proteins in Utibron Neohaler).
- Asthma (monotherapy).
- Patients using other LABAs.
Drug Interactions
- Beta-blockers: May reduce the bronchodilatory effects of indacaterol and could induce bronchospasm in susceptible individuals.
- Other adrenergic drugs: Additive effects on blood pressure and heart rate.
- Xanthine derivatives, steroids, diuretics: May enhance hypokalemia.
- MAOIs, TCAs, QTc-prolonging agents: May increase cardiovascular effects and risk of arrhythmias.
- Anticholinergics: May enhance anticholinergic side effects.
- CYP3A4 inhibitors/inducers: No dose adjustment is typically needed.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (US FDA); B3 (Australia). The drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Beta-agonists may interfere with uterine contractility.
- Breastfeeding: The effects on nursing infants are unknown. A decision should be made whether to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. Indacaterol and glycopyrrolate and their metabolites have been detected in the milk of lactating rats.
Drug Profile Summary
- Mechanism of Action: Bronchodilation by beta2-adrenergic receptor agonism (indacaterol) and muscarinic receptor antagonism (glycopyrrolate).
- Side Effects: Common: Upper respiratory tract infection, nasopharyngitis, runny/stuffy nose, headache, cough, dizziness, back pain. Serious: Angioedema, arrhythmias, paradoxical bronchospasm, worsening glaucoma, urinary retention.
- Contraindications: Hypersensitivity, asthma (monotherapy), concomitant use of other LABAs.
- Drug Interactions: Beta-blockers, other adrenergic drugs, xanthines, steroids, diuretics, MAOIs, TCAs, QTc-prolonging agents, anticholinergics.
- Pregnancy & Breastfeeding: Use with caution if benefits outweigh risks. Not recommended during breastfeeding.
- Dosage: Adults: One capsule inhaled twice daily (Utibron Neohaler) or once daily (Ultibro Breezhaler). Not for pediatric use.
- Monitoring Parameters: Lung function (FEV1, FVC), heart rate, blood pressure, blood glucose, serum potassium, signs of CNS stimulation, glaucoma.
Popular Combinations
- Not applicable. Glycopyrrolate + Indacaterol is a fixed-dose combination and is not typically combined with other inhaled bronchodilators.
Precautions
- General Precautions: Assess for pre-existing conditions like heart problems, narrow-angle glaucoma, urinary retention, diabetes, hyperthyroidism.
- Specific Populations:
- Pregnant Women: Use with caution if benefits outweigh risks.
- Breastfeeding Mothers: Not recommended.
- Children & Elderly: Not for pediatric use. No specific dose adjustments for the elderly.
- Lifestyle Considerations: Monitor blood pressure, avoid alcohol (may increase dizziness), caution while driving or operating machinery.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Glycopyrrolate + Indacaterol?
A: One capsule inhaled twice daily (morning and evening) for Utibron Neohaler or one capsule once daily for Ultibro Breezhaler via the respective inhaler devices.
Q2: Can Glycopyrrolate + Indacaterol be used to treat asthma?
A: No, this medication is not indicated for asthma. It is specifically for the maintenance treatment of COPD.
Q3: What are the most common side effects?
A: Common side effects include runny or stuffy nose, headache, cough, nasopharyngitis, upper respiratory tract infection, back pain, dizziness, hypertension, and urinary tract infection.
Q4: Are there any serious side effects I should be aware of?
A: Yes, although rare, serious side effects can include paradoxical bronchospasm, angioedema, cardiac arrhythmias, worsening of narrow-angle glaucoma, and urinary retention. Monitor for these and advise patients to seek immediate medical attention if they occur.
Q5: Can this medication be used during pregnancy or breastfeeding?
A: It should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. It is generally not recommended during breastfeeding.
Q6: What should I do if a patient misses a dose?
A: Instruct the patient to inhale the missed dose as soon as remembered. However, if it is close to the time for the next dose, skip the missed dose and take the next dose at the regular time. Do not double the dose to catch up.
Q7: Can Glycopyrrolate + Indacaterol be used with other COPD medications?
A: It should not be used concomitantly with other LABAs. Caution is advised with other anticholinergics. Inform your doctor about all other medications the patient is taking.
Q8: How does this drug differ from a rescue inhaler?
A: Glycopyrrolate + Indacaterol is a maintenance medication for long-term control of COPD symptoms. It is not a rescue inhaler and should not be used to treat acute episodes of shortness of breath. Patients should continue to use their rescue inhaler as prescribed.
Q9: Are there any drug interactions I should be aware of?
A: Yes, significant interactions can occur with beta-blockers, other adrenergic drugs, xanthines, steroids, diuretics, MAOIs, TCAs, some antiarrhythmics and other anticholinergics. Carefully review the patient’s medication list for potential interactions.
Q10: How should patients store this medication?
A: Store the capsules in the blister pack until immediately before use. Keep the inhaler device dry and clean. Store at room temperature, away from excessive heat and moisture.
