Beclomethasone Dipropionate/ Formoterol Fumarate Dihydrate

Registered South African indications:

• Asthma

Contraindications

• Hypersensitivity to the active ingredients or any of the excipients in this combination product

Cautions

• Pregnancy
• Breastfeeding
• Renal impairment
• Hepatic impairment
• Cardiac arrhythmias
• Third degree atrioventricular block
• Tachyarrhythmias
• Idiopathic subvalvular aortic stenosis
• Hypertrophic obstructive cardiomyopathy
• Severe heart disease
• Acute myocardial infarction
• Ischaemic heart disease
• Congestive heart failure
• Occlusive vascular diseases
• Severe or unstable asthma
• Arteriosclerosis
• Arterial hypertension
• Aneurysm
• Known or suspected prolongation of QTc interval
• Thyrotoxicosis
• Diabetes mellitus
• Phaeochromocytoma
• Hypokalaemia
• Active or latent pulmonary tuberculosis
• Viral infection in airways
• Fungal infection in airways
• Abrupt withdrawl of treatment
• Prolonged treatment at high doses
• Children <16 years on high doses
• Smoking
• Low body mass index (BMI)
• Chronic obstructive pulmonary disease
• Trauma or surgery
• Patients transferring from oral to inhaled corticosteroids
• May impair the ability to drive and operate machinery

Forms avail. in SA and covered in this monograph: inj

Chronic asthma 

Beclometasone Dipropionate/ Formoterol Fumarate
100/6 (µg)

• Inhaled (inh): Initial: 1-2 inhalations, 12hrly; Max: 4 inhalations/ 24hrs 

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The starting dose should be based on asthma severity

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Not intended for the initial management of asthma

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Patients should rinse their mouth, gargle with water or brush teeth after inhalation

Not established for use in children below 18 years

Pregnancy

• Caution; not recommended
• There are no relevant clinical data on the use of beclometasone dipropionate and formoterol combination in pregnant women. Animal studies using beclometasone dipropionate and formoterol combination showed evidence of toxicity to reproduction after high systemic exposure  
• Because of the tocolytic actions of beta-2-sympathomimetic agents, particular care should be exercised in the run-up to delivery  
• There is no experience with or evidence of safety of propellant HFA-134a in human pregnancy. However, studies of the effect of HFA-134a on reproductive function and embryofoetal development in animals have revealed no clinically relevant adverse effects
• Formoterol should not be recommended for use during pregnancy and particularly at the end of pregnancy or during labour unless there is no other (safer) established alternative. Beclometasone dipropionate and formoterol combination should only be used during pregnancy if the expected benefits outweigh the potential risks

Breastfeeding

• Caution; not recommended 
• There are no relevant clinical data on the use of beclometasone dipropionate and formoterol combination in lactation in humans  
• Although no data from animal experiments are available, it is reasonable to assume that beclometasone dipropionate is secreted in milk, like other corticosteroids. While it is not known whether formoterol passes into human breast milk, it has been detected in the milk of lactating animals  
• There is no experience with or evidence of safety of propellant HFA-134a in human breastfeeding. However, studies of the effect of HFA-134a on reproductive function and embryofoetal development in animals have revealed no clinically relevant adverse effects
• Administration of beclometasone dipropionate and formoterol combination to women who are breastfeeding should only be considered if the expected benefits outweigh the potential risks  

Renal Impairment

• Caution; no information available 

Hepatic Impairment

• Caution; no information available

Elderly

• No dose adjustment recommended 

Porphyria Information

• Not porphyrinogenic (NP) 

Drugs in Sport

• Permitted - No Warnings

Central Nervous System Disorders

• Restlessness
• Psychomotor hyperactivity
• Sleep disorders
• Anxiety
• Depression
• Aggression
• Behavioural changes
• Headache
• Tremor
• Dizziness

Cardiovascular Disorders

• Palpitations
• Prolonged QT interval
• Electrocardiogram changes
• Tachycardia
• Tachyarrhythmia
• Atrial fibrillation
• Ventricular extrasystoles
• Angina pectoris
• Increased blood pressure
• Decreased blood pressure

Respiratory Disorders

• Pharyngitis
• Sinusitis
• Rhinitis
• Dysphonia
• Cough (including productive cough)
• Throat irritation
• Asthmatic crisis
• Paradoxical bronchospasm
• Dyspnoea
• Exacerbation of asthma
• Pneumonia

Gastrointestinal Disorders

• Oral fungal infection
• Oropharyngeal candidiasis
• Oesophageal candidiasis  
• Gastroenteritis
• Diarrhoea
• Dry mouth
• Dyspepsia
• Dysphagia
• Burning sensation of the lips
• Nausea
• Dysgeusia

Genitourinary Disorders

• Vulvovaginal candidiasis
• Nephritis

Endocrine and Metabolic Disorders

• Adrenal suppression
• Acute adrenal crisis
• Hypokalaemia
• Hyperglycaemia
• Increased free fatty acids
• Increased blood insulin
• Increased blood ketone bodies
• Decreased blood cortisol
• Cushing's syndrome
• Cushingoid features

Musculoskeletal Disorders

• Muscle spasms
• Myalgia
• Growth retardation (in children and adolescents)
• Decreased bone density

Skin and Subcutaneous Tissue Disorders

• Pruritis
• Rash
• Hyperhidrosis
• Urticaria
• Angioedema

Immune, Blood and Lymphatic System Disorders

• Granulocytopenia
• Thrombocytopenia
• Allergic dermatitis  
• Hypersensitivity reactions
  - Erythema
  - Lips, face, eye and pharyngeal oedema
• Hyperaemia
• Flushing
• Increased platelet count

Sensory Disorders

• Glaucoma
• Cataract
• Blurred vision
• Otosalpingitis

Others

• Peripheral oedema
• Increased C-reactive protein  
• Influenza

• CYP3A inhibitors
• Ritonavir
• Cobicstat
• Beta-blockers (including eye drops)
• Beta-adrenergic agents
• Theophylline
• Quinidine
• Disopyramide
• Procainamide
• Phenothiazines
• Antihistamines
• Monoamine oxidase inhibitors
• Tricyclic antidepressants
• L-dopa
• L-thyroxine
• Oxytocin
• Furazolidone
• Procarbazine
• Halogenated anaesthetics
• Hypokalaemic agents
• Xanthine derivatives
• Steroids
• Diuretics
• Digitalis glycosides
• Disulfiram
• Metronidazole
• Alcohol

None routine

Precautions for use

• For treatment of acute asthma attacks, patients should be advised to have their rapid-acting bronchodilator available at all times, either beclometasone dipropionate/ formoterol fumarate dihydrate or a separate rapid-acting bronchodilator (for patients using beclometasone dipropionate/ formoterol fumarate dihydrate as maintenance therapy only)
• Patients should be reminded to take beclometasone dipropionate/ formoterol fumarate dihydrate daily as prescribed even when asymptomatic. The reliever inhalations should be taken in response to asthma symptoms but are not intended for regular prophylactic use, such as before exercise. For such use, a separate rapid-acting bronchodilator should be considered
• Once asthma symptoms are controlled, consideration may be given to gradually reducing the dose of beclometasone dipropionate/ formoterol fumarate dihydrate. Regular review of patients as treatment is stepped down is important. The lowest effective dose of beclometasone dipropionate/ formoterol fumarate dihydrate should be used

Worsening of symptoms

• Increasing use of rescue bronchodilators indicates a worsening of the underlying condition and warrants a reassessment of the asthma therapy. Sudden and progressive deterioration in control of asthma is potentially life-threatening and the patient should undergo urgent medical assessment. Consideration should be given to the need for increased treatment with corticosteroids, either inhaled or oral therapy, or antibiotic treatment if an infection is suspected
• Patients should not be initiated on beclometasone dipropionate/ formoterol fumarate dihydrate during an exacerbation, or if they have significantly worsening or acutely deteriorating asthma. Serious asthma-related adverse events and exacerbations may occur during treatment. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation of beclometasone dipropionate/ formoterol fumarate dihydrate

Paradoxical bronchospasm

• As with other inhalation therapy, paradoxical bronchospasm may occur with an immediate increase in wheezing and rapidness of breath after dosing. This should be treated immediately with a fast-acting inhaled bronchodilator. Treatment should be discontinued immediately and the patient assessed and alternative therapy instituted if necessary

Beclometasone

Beclometasone dipropionate given by inhalation has a glucocorticoid anti-inflammatory action within the lungs, resulting in reduced symptoms and exacerbations of asthma. The anti-inflammatory action involves the control of protein synthesis, depression of the migration of polymorphonuclear leukocytes and fibroblasts, the reverse of capillary permeability and lysosomal stabilization at the cellular level to prevent or control inflammation.

Formoterol

Formoterol fumarate is a selective beta-2 adrenoceptor agonist that relaxes bronchial smooth muscle, resulting in rapid bronchodilating effects in patients with reversible airways obstruction.

 

COMBINATION PREPARATIONS

Beclometasone Dipropionate/Formoterol Fumarate Dihydrate

Inhaler 100μg/6μg

• Innuvair (Adcock Ingram)