Onbrez Breezhaler

/ Novartis

Adults: The recommended dosage is the once-daily inhalation of the content of one 150 microgram capsule using the inhaler. The dosage should only be increased on medical advice. Once-daily inhalation of the content of one 300 microgram capsule, using the inhaler, has been shown to provide additional clinical benefit to some patients, e.g. with regard to breathlessness, particularly for patients with severe COPD. The maximum dose is 300 microgram once-daily.
Dosing in special populations: No dosage adjustment is required for geriatric patients, patients with mild and moderate hepatic impairment, or renally impaired patients. No data is available for subjects with severe hepatic impairment. Should not be used in patients under 18 years of age.
Method of administration: Capsules must be administered only by the oral inhalation route and only using the product’s inhaler. Capsules must not be swallowed. This product should be administered at the same time of the day each day. If a dose is missed, the next dose should be taken at the usual time the next day. ONBREZ BREEZHALER capsules must always be stored in the blister, and only removed IMMEDIATELY BEFORE USE.
Patients should be instructed on how to administer the product correctly. Patients who do not experience improvement in breathing should be asked if they are swallowing the medicine rather than inhaling it.

Maintenance of bronchodilator treatment of airflow obstruction in adult patients with chronic obstructive pulmonary disease (COPD).

Hypersensitivity to the active substance, to lactose or to any of the excipients.

Asthma: It should not be used in asthma due to the absence of long-term outcome data in asthma with this drug.
Hypersensitivity: Immediate hypersensitivity reactions have been reported after administration of this drug. If signs suggesting allergic reactions (in particular, difficulties in breathing or swallowing, swelling of tongue, lips and face, urticaria, skin rash) occur,it should be discontinued immediately and alternative therapy instituted.
Paradoxical bronchospasm: As with other inhalation therapy, administration may result in paradoxical bronchospasm that may be life-threatening. If paradoxical bronchospasm occurs, It should be discontinued immediately and alternative therapy instituted.
Deterioration of disease :This drug is not indicated for the initial treatment of acute episodes of bronchospasm, i.e., as a rescue therapy. In case of deterioration of COPD whilst on treatment, a re-evaluation of the patient and the COPD treatment regimen should be undertaken. An increase in the daily dose  beyond the maximum dose of 300 microgram is not appropriate.
Systemic effects: Although no clinically relevant effect on the cardiovascular system is usually seen after the administration at the recommended doses, as with other beta2adrenergic agonists, indacaterol should be used with caution in patients with cardiovascular disorders (coronary artery disease, acute myocardial infarction, cardiac arrhythmias, hypertension), in patients with convulsive disorders or thyrotoxicosis, and in patients who are unusually responsive to beta2-adrenergic agonists. As with other inhaled beta2-adrenergic drugs, It should not be used more often or at higher doses than recommended. It should not be used in conjunction with other long-acting beta2adrenergic agonists or medications containing long-acting beta2-adrenergic agonists.
Cardiovascular effects: Like other beta2-adrenergic agonists, indacaterol may produce a clinically significant cardiovascular effect in some patients as measured by increases in pulse rate, blood pressure, and/or symptoms. In case such effects occur, the drug may need to be discontinued. In addition, beta-adrenergic agonists have been reported to produce ECG changes, such as flattening of the T wave, prolongation of QT interval, and ST segment depression, although the clinical significance of these observations is unknown. Therefore, long-acting beta2-adrenergic agonists such as Onbrez Breezhaler should be used with caution in patients with known or suspected prolongation of the QT interval or treated with medicinal products affecting the QT interval.
Hypokalemia: Beta2-adrenergic agonists may produce significant hypokalemia in some patients, which has the potential to produce adverse cardiovascular effects. The decrease in serum potassium is usually transient, not requiring supplementation. In patients with severe COPD, hypokalaemia may be potentiated by hypoxia and concomitant treatment which may increase the susceptibility to cardiac arrhythmias.
Hyperglycemia: Inhalation of high doses of beta2-adrenergic agonists may produce increases in plasma glucose. Upon initiation of treatment plasma glucose should be monitored more closely in diabetic patients. During clinical studies, clinically notable changes in blood glucose were generally more frequent by 1-2%  at the recommended doses than on placebo. This drug has not been investigated in patients with not well controlled diabetes mellitus.
Excipients: The capsules contain lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
See prescribing information for full details.

The most common adverse drug reactions at the recommended doses were nasopharyngitis, upper respiratory tract infection, cough, headache and muscle spasms. These were in the vast majority mild or moderate and became less frequent when treatment was continued.
See prescribing information for full details.

Drugs known to prolong QTc interval: as other beta2-adrenergic agonists, should be administered with caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or drugs known to prolong the QT interval, as any effect of these on the QT interval may be potentiated. Drugs known to prolong the QT-interval may increase the risk of ventricular arrhythmia.
Sympathomimetic agents: Concomitant administration of other sympathomimetic agents (alone or as part of combination therapy) may potentiate the undesirable effects of this drug.
Hypokalemia: Concomitant treatment with methylxanthine derivatives, steroids, or non-potassium-sparing diuretics may potentiate the possible hypokalaemic effect of beta2-adrenergic agonists.
Beta-adrenergic blockers: Beta-adrenergic blockers may weaken or antagonise the effect of beta2-adrenergic agonists. Therefore it should not be given together with beta-adrenergic blockers (including eye drops) unless there are compelling reasons for their use. Where required, cardioselective beta-adrenergic blockers should be preferred, although they should be administered with caution.
Metabolic and transporter based drug interaction: Inhibition of the key contributors of indacaterol clearance, CYP3A4 and P-gp, has no impact on safety of therapeutic doses. Drug interaction studies were carried out using potent and specific inhibitors of CYP3A4 and P-gp (i.e., ketoconazole, erythromycin, verapamil and ritonavir). Verapamil was used as the prototypic inhibitor of Pgp and resulted in 1.4- to two-fold increase in AUC and 1.5-fold increase in Cmax. Coadministration of erythromycin with this drug resulted in an increase of 1.4- to 1.6-fold for AUC and 1.2 fold for Cmax. Combined inhibition of P-gp and CYP3A4 by the very strong dual inhibitor ketoconazole caused a 2-fold and 1.4-fold increase in AUC and Cmax, respectively. Concomitant treatment with ritonavir, another dual inhibitor of CYP3A4 and P-gp, resulted in a 1.6- to 1.8-fold increase in AUC whereas Cmax was unaffected.Taken together, the data suggest that systemic clearance is influenced by modulation of both P-gp and CYP3A4 activities and that the 2-fold AUC increase caused by the strong dual inhibitor ketoconazole reflects the impact of maximal combined inhibition. The magnitude of exposure increases due to drug interactions does not raise any safety concerns given the safety experience of treatment in clinical trials of up to one year at doses two- to four-fold the recommended therapeutic doses. it has not been shown to cause drug interactions with comedications. In vitro investigations have indicated that indacaterol has negligible potential to cause metabolic interactions with medications at the systemic exposure levels achieved in clinical practice.
See prescribing information for full details.

Pregnancy: No clinical data on exposed pregnancies in COPD patients are available. The potential risk for humans is unknown. Because there are no adequate and well-controlled studies in pregnant women, indacaterol should be used during pregnancy only if the expected benefit justifies the potential risk to the fetus.
Lactation: It is not known whether indacaterol passes into human breast milk. Available pharmacokinetic/toxicological data in animals have shown excretion of indacaterol/metabolites in milk. A risk to the breast-fed child cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Onbrez Breezhaler therapy, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
See prescribing information for full details.

In COPD patients single doses of 10 times the maximum recommended therapeutic dose were associated with a moderate increase in pulse rate, systolic blood pressure increase and QTc interval.  An overdose of indacaterol is likely to lead to exaggerated effects typical of beta2-adrenergic stimulants i.e., tachycardia, tremor, palpitations, headache, nausea, vomiting, drowsiness, ventricular arrhythmias, metabolic acidosis, hypokalaemia and hyperglycemia. Supportive and symptomatic treatment is indicated. In serious cases, patients should be hospitalized. Use of cardioselective beta-blockers may be considered, but only under the supervision of a physician and with extreme caution since the use of beta-adrenergic blockers may provoke bronchospasm.

Storage: Do not store above 30°C and protect from moisture.