Hypersensitivity to beclometasone dipropionate, formoterol fumarate dihydrate and/or any of the excipients of Beclometasone/Formoterol.
Beclometasone/Formoterol contains beclometasone dipropionate and formoterol fumarate dihydrate, the type and severity of adverse reactions associated with each of the compounds may be expected. There is no incidence of additional adverse events following concurrent administration of the 2 compounds.
Adverse effects which have been associated with beclometasone dipropionate and formoterol administered as a fixed combination and as single agents are given as follows, listed by system organ class. Frequencies are defined as: Very common (≥1/10), common (≥1/100 and <1/10), uncommon (≥1/1,000 and <1/100), rare (≥1/10,000 and <1/1,000) and very rare (≤1/10,000).
Common and uncommon adverse reactions were derived from clinical trials in asthmatic and COPD patients.
Infections and Infestations: Common: Pharyngitis, oral candidiasis. Uncommon: Influenza, oral fungal infection, oropharyngeal and esophageal candidiasis, vulvovaginal candidiasis, gastroenteritis, sinusitis, rhinitis, pneumonia*.
Blood and Lymphatic System Disorders: Uncommon: Granulocytopenia. Very Rare: Thrombocytopenia.
Immune System Disorders: Uncommon: Allergic dermatitis. Very Rare: Hypersensitivity reactions including erythema, lips, face, eye and pharyngeal edema.
Endocrine Disorders: Very Rare: Adrenal suppression.
Metabolism and Nutrition Disorders: Uncommon: Hypokalemia and hyperglycemia.
Psychiatric Disorders: Uncommon: Restlessness. Unknown: Psychomotor hyperactivity, sleep disorders, anxiety, depression, aggression, behavioral changes (predominantly in children).
Nervous System Disorders:
Common: Headache. Uncommon: Tremor, dizziness.Eye Disorders: Very Rare: Glaucoma, cataract.
Ear and Labyrinth Disorders: Uncommon: Otosalpingitis.
Cardiac Disorders: Uncommon: Palpitations, prolonged QT electrocardiogram interval, change in electrocardiogram, tachycardia, tachyarrhythmia, atrial fibrillation*. Rare: Ventricular extrasystoles, angina pectoris.
Vascular Disorders: Uncommon: Hyperemia, flushing.
Respiratory, Thoracic and Mediastinal Disorders: Common: Dysphonia. Uncommon: Rhinitis, cough, productive cough, throat irritation, asthmatic crisis. Rare: Paradoxical bronchospasm. Very Rare: Dyspnea, exacerbation of asthma.
Gastrointestinal Disorders: Uncommon: Diarrhea, dry mouth, dyspepsia, dysphagia, burning sensation of the lips, nausea, dysgeusia.
Skin and Subcutaneous Tissue Disorders: Uncommon: Pruritus, rash, hyperhidrosis, urticaria. Rare: Angioedema.
Musculoskeletal, Connective Tissue and Bone Disorders: Uncommon: Muscle spasms, myalgia. Very Rare: Growth retardation in children and adolescents.
Renal and Urinary Disorders: Rare: Nephritis.
General Disorders and Administration Site Conditions: Very Rare: Peripheral edema.
Investigations: Uncommon: Increased C-reactive protein, platelet count, free fatty acids, blood insulin and blood ketone body, decreased blood cortisol. Rare: Increased and/or decreased blood pressure. Very Rare: Decreased bone density.
*One related non-serious case of pneumonia was reported by 1 patient treated with the drug in a pivotal clinical trial in COPD patients. Other adverse reactions observed in COPD clinical trials were: Reduction of blood cortisol and atrial fibrillation.
As with other inhalation therapy, paradoxical bronchospasm may occur.
Among the observed adverse reactions those typically associated with formoterol are: Hypokalemia, headache, tremor, palpitations, cough, muscle spasms and QTc interval prolongation.
Adverse reactions typically associated with the administration of beclometasone dipropionate are:
Oral fungal infections, oral candidiasis, dysphonia, throat irritation.Dysphonia and candidiasis may be relieved by gargling or rinsing the mouth with water or brushing the teeth after using Beclometasone/Formoterol.
Symptomatic candidiasis can be treated with topical antifungal therapy whilst continuing the treatment with Beclometasone/Formoterol.
Systemic effects of inhaled corticosteroids (eg, beclometasone dipropionate) may occur particularly when administered at high doses or prescribed for prolonged periods. These may include adrenal suppression, decrease in bone mineral density, growth retardation in children and adolescents, cataract and glaucoma.
Hypersensitivity reactions including rash, urticaria, pruritus and erythema, and edema of the eyes, face, lips and throat may also occur.
Reporting of Suspected Adverse Reactions: Reporting suspected adverse reactions after authorization of Beclometasone/Formoterol is important. It allows continued monitoring of the benefit/risk balance of Beclometasone/Formoterol. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system.
Asthma: Regular treatment of asthma where use of a combination product (inhaled corticosteroid and long-acting β2-agonist) is appropriate in patients not adequately controlled with inhaled corticosteroids and 'as needed' inhaled rapid-acting β2-agonist or patients already adequately controlled on both inhaled corticosteroids and long-acting β2-agonists.
COPD: Symptomatic treatment of patients with severe COPD (FEV1 <50% predicted normal) and a history of repeated exacerbations, who have significant symptoms despite regular therapy with long-acting bronchodilators.
Each actuation/metered-dose (ex-valve) contains beclometasone dipropionate 100 mcg and formoterol fumarate dihydrate 6 mcg corresponding to beclometasone dipropionate 84.6 mcg and formoterol fumarate dihydrate 5 mcg as deliverable dose, respectively.
Asthma: Adults (≥18 years): Maintenance Therapy and Maintenance Reliever Therapy: Recommended Dose: 1 or 2 inhalations twice daily. Maximum Dose: 4 inhalations daily.
Maintenance Reliever Therapy: Taken as regular maintenance treatment and patients are advised to have separate 'as needed' rapid-acting bronchodilator available for rescue use at all times.
Not Fully-controlled Asthma and in Need of Reliever Medication: History of Asthma Exacerbations Requiring Medical Intervention: Recommended Dose: 1 inhalation twice daily (1 in the morning and 1 in the evening). Maximum Dose: 8 inhalations.
Patients requiring frequent use of rescue inhalations daily should be strongly recommended to seek medical advice. Their asthma should be reassessed and the maintenance therapy should be reconsidered.
Children and Adolescents <18 years: There is no experience with the drug in children and adolescents <18 years. Therefore the drug is not recommended for children and adolescents <18 years until further data become available.
Patients should be regularly reassessed by a physician, so that the dosage of Beclometasone/Formoterol remains optimal and is only changed on medical advice. The dose should be titrated to the lowest dose at which effective control of symptoms is maintained. When control of symptoms is maintained with the lowest recommended dosage, then the next step could include a test of inhaled corticosteroid alone.
COPD: Adults ≥18 years: Recommended Dose: 2 inhalations twice daily.
Elderly: There is no need to adjust the dose in elderly patients.
Hepatic/Renal Impairment: There are no data available for use of Beclometasone/Formoterol in patients with hepatic or renal impairment.
Administration: Beclometasone/Formoterol is for inhalation use.
Beta-blockers (including eye drops) should be avoided in asthmatic patients. If β-blockers are administered for compelling reasons, the effect of formoterol will be reduced or abolished.
On the other hand, concomitant use of other β-adrenergic drugs can have potentially additive effects, therefore, caution is required when theophylline or other β-adrenerigic drugs are prescribed concomitantly with formoterol.
Concomitant treatment with quinidine, disopyramide, procainamide, phenothiazines, antihistamines, monoamine oxidase inhibitors and tricyclic antidepressants can prolong the QTc interval and increase the risk of ventricular arrhythmias.
In addition L-dopa, L-thyroxine, oxytocin and alcohol can impair cardiac tolerance towards β2-sympathomimetics.
Concomitant treatment with monoamine oxidase inhibitors including agents with similar properties eg, furazolidone and procarbazine may precipitate hypertensive reactions.
There is an elevated risk of arrhythmias in patients receiving concomitant anesthesia with halogenated hydrocarbons.
Concomitant treatment with xanthine derivatives, steroids or diuretics may potentiate a possible hypokalemic effect of β2-agonists.
Hypokalemia may increase the disposition towards arrhythmias in patients who are treated with digitalis glycosides.
Beclometasone/Formoterol contains a small amount of ethanol. There is a theoretical potential for interaction in particularly sensitive patients taking disulfiram or metronidazole.
