Ulunar Breezhaler (Glycopyrronium)
Ulunar Breezhaler (Glycopyrronium) Uses, Dosage, Side Effects, Food Interaction and all others data.
Glycopyrronium is a long-acting, specific antimuscarinic agent, in clinical medicine often called an anticholinergic. It has a similar affinity to the subtypes of muscarinic receptors M1 to M5. In the airways, inhibition of M3-receptors at the smooth muscle results in relaxation. The high potency and slow receptor dissociation found its clinical correlate in significant and long-acting bronchodilation in patients with COPD.
Glycopyrronium is a quaternary ammonium compound that is one of the most commonly prescribed long acting muscarinic antagonists. Glycopyrronium slowly dissociated from muscarinic receptors, leading to a long duration of action. It has a wider therapeutic index than other anticholinergic medications, such as tiotropium. Patients should be counselled regarding the risk of worsening urinary retention, risk of overheating, and transient blurred vision.
Indacaterol is a long acting β2-adrenergic agonist. It relaxes the bronchial smooth muscle by selective action on β2-receptor which acts locally in the lungs and with little effect on heart rate.
When inhaled, Indacaterol acts locally in the lung as a bronchodilator. The pharmacological effects of β2-adrenoceptor agonist drugs, including indacaterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic monophosphate. Increased cyclic AMP levels cause relaxation of bronchial smooth muscle.
Bronchodilator drugs are the foundation for the treatment of chronic obstructive pulmonary disease. The principal inhaled bronchodilator treatments used are β(2) -agonists and anticholinergics, either alone or in combination. Currently available β(2) -agonists are of either short duration and used multiple times/day, or of long duration, which requires twice-daily administration. Indacaterol is considered an ultra-long-acting β(2) -agonist and was recently approved for use in the United States. Its duration of action is approximately 24 hours, allowing for once-daily administration. Furthermore, this chiral compound it is given as the R-enantiomer and acts as a full agonist. Cough was the most commonly reported adverse effect with use of indacaterol. Compared to salmeterol, it has 35% more agonist activity. Cough usually occurred within 15 seconds of inhalation of the drug, lasted around 6 seconds, was not associated with bronchospasm, and did not cause discontinuation of the drug. Otherwise, the drug's safety profile was similar to that of other bronchodilators. [PMID: 22499359]
| Trade Name | Ulunar Breezhaler (Glycopyrronium) |
| Generic | Glycopyrronium + Indacaterol |
| Type | |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | Austria, Belgium, Bulgaria, Cyprus, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Latvia, Liechtenstein, Lithuania, Luxembourg, Malta, Netherlands, Norway, Poland, Portugal, Romania, Slovakia, Slovenia, Spain, Sweden, United Kingdom |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Maintenance bronchodilator treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD).
Indacaterol is used for the treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.
Indacaterol is a long-acting β2-adrenergic agonist used for long-term, once-daily maintenance bronchodilator treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema.
Ulunar Breezhaler (Glycopyrronium) is also used to associated treatment for these conditions: Airway Obstruction, Chronic Obstructive Pulmonary Disease (COPD), Increased upper airway secretion, Peptic Ulcer, Primary Axillary Hyperhidrosis, Sialorrhea (Excessive Drooling), Cardiac vagal inhibitory reflexes, Cardiac vagal inhibitory reflexes caused by General Surgery, Cardiac vagal inhibitory reflexes caused by Medication, Gastric secretions, Peripheral muscarinic effectsAsthma, Chronic Obstructive Pulmonary Disease (COPD), Maintenance
How Ulunar Breezhaler (Glycopyrronium) works
Glycopyrronium is a muscarinic antagonist with the highest affinity for M1 receptors, followed by M3, M2/M4, and M5.
Muscarinic receptors M1 to M4 are found in the lung, although M3 is predominantly responsible for bronchoconstriction and airway secretions. Secretions from salivary and sweat glands, as well as gastric acid secretions, are also predominantly mediated by the M3 receptor. Salivary and gastric acid secretions are also partially mediated by the M1 receptor. Antagonism of these receptors decreases the volume of their respective secretions, and in the case of the gastrointestinal system, reduces the acidity of the stomach.
In the cardiovascular system, muscarinic receptors M1 to M5 are all present, however the function of M5 has not been described in literature. Under normal circumstances, stimulation of the vagal nerve lowers the heart rate, potentially leading to intraoperative bradycardia. Studies in mice suggest that this stimulation is predominantly mediated by the M3 receptor, and mutant knockout mice are not susceptible to these effects.
Indacaterol works by stimulating adrenergic beta-2 receptors in the smooth muscle of the airways. This causes relaxation of the muscle, thereby increasing the diameter of the airways, which become constricted in asthma and COPD. It is also long acting due to its high affinity to the lipid raft domains in the airway membrane so it slowly dissociates from the receptors. Indacaterol also has a high intrinsic efficacy so it is also very rapid acting - onset of action occurs within 5 minutes.
The pharmacological effects of beta2-adrenoceptor agonist drugs, including indacaterol, 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 monophosphate). Increased cyclic AMP levels cause relaxation of bronchial smooth muscle. In vitro studies have shown that indacaterol has more than 24-fold greater agonist activity at beta2-receptors compared to beta1-receptors and 20-fold greater agonist activity compared to beta3-receptors. This selectivity profile is similar to formoterol. The clinical significance of these findings is unknown.
Dosage
Ulunar Breezhaler (Glycopyrronium) dosage
The recommended dosage of Glycopyrronium is the inhalation of the contents of one capsule once daily with the ConviHaler device at the same time of day.
Indacaterol capsules must not be swallowed as the intended effects on the lungs will not be obtained. The contents of Indacaterol capsules are only for oral inhalation and should only be used with thedevice.
The recommended dosage of Indacaterol is the once-daily inhalation of the contents of one 75/150 mcg Indacaterol capsule using the device.
Indacaterol should be administered once daily every day at the same time of the day by the orally inhaled route only. If a dose is missed, the next dose should be taken as soon as it is remembered. Do not use Indacaterol more than one time every 24 hours.
Side Effects
Inhaled medicines may cause inhalation-induced bronchospasm, dehydration, dry mouth, constipation, dizziness, insomnia, skin and subcutaneous tissue disorders, immune system disorders.
The most commonly reported adverse effects were cough, nasopharyngitis, headache, nausea, oropharyngeal pain. Some other also reported of hypersensitivity reactions, paradoxical bronchospasm, tachycardia, pruritis and dizziness.
Toxicity
Patients presenting with an overdose typically present with flushing, hyperthermia, tachycardia, ileus, urinary retention, loss of ocular accommodation, light sensitivity, mydriasis, nausea, vomiting, dizziness, light headedness, and obstipation. Patients should be treated with symptomatic and supportive therapy, which may include the use of catheters for urinary retention, cardiovascular support, airway maintenance, ventilation, or neostigmine.
The oral LD50 in mice is 570 mg/kg, and in rats is 709 mg/kg. The intraperitoneal LD50 in mice is 90 mg/kg, and in rats is 196 mg/kg.
The expected signs and symptoms associated with overdosage of indacaterol are those of excessive beta-adrenergic stimulation and occurrence or exaggeration of any of the signs and symptoms, e.g., angina, hypertension or hypotension, tachycardia, with rates up to 200 bpm, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, muscle cramps, nausea, dizziness, fatigue, malaise, hypokalemia, hyperglycemia, metabolic acidosis and insomnia. As with all inhaled sympathomimetic medications, cardiac arrest and even death may be associated with an overdose of indacaterol.
Precaution
Glycopyrronium, as a once-daily maintenance bronchodilator, should not be used for the initial treatment of acute episodes of bronchospasm, i.e. rescue therapy. Immediate hypersensitivity reactions may occur after administration of Glycopyrronium inhalation powder. As with other anticholinergic drugs, Glycopyrronium should be used with caution in patients with narrow-angle glaucoma, prostatic hyperplasia or bladder-neck obstruction.
Rarely, serious (sometimes fatal) breathing problems have happened to people with asthma using a long-acting inhaled beta agonist (salmeterol). Since Indacaterol is similar to salmeterol, it might cause these serious breathing problems. Indacaterol has not been shown to be safe or effective to treat asthma and is not approved for this use.
Interaction
Although no formal drug interaction studies have been performed, Glycopyrronium inhalation powder has been used concomitantly with other drugs, commonly used in the treatment of COPD, including sympathomimetic bronchodilators, methylxanthines, oral and inhaled steroids without clinical evidence of drug interactions.
Indacaterol shows interaction with Adrenergic Drugs, Xanthine Derivatives, Steroids, or Diuretics. Concomitant treatment with xanthine derivatives, steroids, or diuretics may potentiate any hypokalemic effect of Indacaterol. The ECG changes or hypokalemia that may result from the administration of non-potassium sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by β2-agonists. Indacaterol, as with other β2-agonists, should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or other drugs known to prolong the QTc interval. β-adrenergic receptor antagonists (beta-blockers) and Indacaterol may interfere with the effect of each other when administered concurrently.
Volume of Distribution
The mean volume of distribution in patients aged 1-14 years old is 1.3-1.8 L/kg, with a range of 0.7-3.9 L/kg. The volume of distribution in adults aged 60-75 years is 0.42 ± 0.22 L/kg.
After intravenous infusion the volume of distribution (Vz) of indacaterol was 2,361 L to 2,557 L indicating an extensive distribution.
Elimination Route
In adults, a 66 mg topical dose of glycopyrronium reaches a Cmax of 0.08 ± 0.04 ng/mL, with a Tmax of 1 hour, and an AUC0-24 of 0.88 ± 0.57 h*ng/mL.
Inhaled glycopyrronium is approximately 40% bioavailable. A 25 µg inhaled solution reaches a Cmax of 34.5 pg/mL, with a Tmax of 0-inf of 255 h*pg/mL.
An 8 µg/kg intramuscular dose reaches a Cmax of 3.47 ± 1.48 µg/L, with a Tmax of 27.48 ± 6.12 minutes, and an AUC of 6.64 ± 2.33 h*g/L.
Oral glycopyrronium has highly variable pharmacokinetics, reaching a mean Cmax of 0.318 ng/mL, a Tmax of 3.1 hours, and an AUC0-24 of 1.74 h*ng/mL.
The median time to reach peak serum concentrations of indacaterol was approximately 15 minutes after single or repeated inhaled doses. Absolute bioavailability of indacaterol after an inhaled dose was on average 43-45%.
Half Life
The half life after inhalation is approximately 33-53 hours. The mean half life of a 6 µg/kg intravenous dose is 0.83 ± 0.27 hours. The mean half life of oral glycopyrronium is 3.0 hours.
Indacaterol serum concentrations declined in a multi-phasic manner with an average terminal half-life ranging from 45.5 to 126 hours. The effective half-life, calculated from the accumulation of indacaterol after repeated dosing with once daily doses between 75 mcg and 600 mcg ranged from 40 to 56 hours which is consistent with the observed time-to-steady state of approximately 12-15 days.
Clearance
A 6 µg/kg intravenous dose has a clearance of 0.54 ± 0.14 L/kg/h. An oral solution has a clearance of 5.28-38.95 L/h/kg in healthy adults and 8.07-25.65 L/h/kg in patients with cerebral palsy.
Renal clearance of indacaterol is, on average, between 0.46 and 1.2 L/h. Serum clearance of indacaterol is 18.8 L/h to 23.3 L/h.
Elimination Route
85% of an intravenous dose was recovered in the urine, with 12 >80% of the recovered dose is the unchanged parent drug. The remainder is recovered as the inactive M9 metabolite.
Renal clearance plays a minor role (about 2 to 6% of systemic clearance) in the elimination of systemically available indacaterol. In a human ADME study where indacaterol was given orally, the fecal route of excretion was dominant over the urinary route. Indacaterol was excreted into human feces primarily as unchanged parent drug (54% of the dose) and, to a lesser extent, hydroxylated indacaterol metabolites (23% of the dose).
Pregnancy & Breastfeeding use
There is a limited amount of data from the use of Glycopyrronium in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity at clinically relevant doses. Glycopyrronium should not be used in pregnant or nursing women unless the expected benefit outweighs any possible risk to the unborn child or the infant.
Pregnancy Category C. There are no adequate and well-controlled studies with Indacaterol powder in pregnant women. Indacaterol powder should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
It is not known that the active component of Indacaterol powder, Indacaterol is excreted in human milk. Because many drugs are excreted in human milk and because Indacaterol has been detected in the milk of lactating rats, caution should be exercised when Indacaterol powder is administered to nursing women.
Contraindication
Hypersensitivity to the active substance or to any of the excipients.
All LABA are contraindicated in patients with asthma without use of a long-term asthma control medication. Indacaterol powder is not indicated for the treatment of asthma. Indacaterol is contraindicated in patients with a history of hypersensitivity to Indacaterol or to any of the ingredients.
Special Warning
Geriatric patients: No dosage adjustment is required for geriatric patients, patients with mild and moderate hepatic impairment, or renal impaired patients.
Hepatic impairment: No data are available for subjects with severe hepatic impairment.
Hepatic use: Not indicated for use in the hepatic impairment. Safety and efficacy have not been established.
Acute Overdose
High doses of Glycopyrronium may lead to anticholinergic signs and symptoms. However, there were no systemic anticholinergic adverse effects following a single inhaled dose of up to 150 micrograms Glycopyrronium in healthy volunteers.
The expected signs and symptoms associated with over dosage of Indacaterol powder are those of excessive beta-adrenergic stimulation and occurrence or exaggeration of any of the signs and symptoms, e.g., angina, hypertension or hypotension, tachycardia, with rates up to 200 bpm, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, muscle cramps, nausea, dizziness, fatigue, malaise, hypokalemia, hyperglycemia, metabolic acidosis and insomnia. As with all inhaled sympathomimetic medications, cardiac arrest and even death may be associated with an over dose of Indacaterol powder.
Storage Condition
Should be stored at temperature not exceeding 25ºC but do not freeze. Should be stored in cool and dry place, protected from light.
Indacaterol capsules must always be stored in the blister, and only removed immediately before use. Keep in a cool & dry place. Keep out of the reach of children.
Innovators Monograph
You find simplified version here Ulunar Breezhaler (Glycopyrronium)
