Indacaterol/ Mometasone Furoate

Registered South African indication:

• Asthma, where use of a combination of a long-acting beta₂-agonist and an inhaled corticosteroid is appropriate

Contraindications

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

Cautions

South African manufacturer recommendations

• Pregnancy
• Breastfeeding
• Severe hepatic impairment
• Adolescents
• Deterioration of disease
• Acute asthma
• Acute episodes of bronchospasm for which a short-acting bronchodilator is required
• Withdrawal of treatment without medical practitioner supervision
• Uncontrolled or worsening asthma symptoms
• Cardiovascular disorders
  - Coronary artery disease
  - Acute myocardial infarction
  - Cardiac dysrhythmias
  - Hypertension
• Seizure disorders
• Hyperthyroidism
• High doses for prolonged periods
• Unusual responsiveness to beta₂-adrenergic agonists
• Known or suspected QT prolongation
• Pre-existing hypokalaemia
• Hypoxia
• Diabetes mellitus
• Medical or surgical emergency situations likely to produce stress
• Pulmonary tuberculosis
• Chronic or untreated infections
• Human immunodeficiency virus (HIV)
• Abrupt withdrawal
• Coadministration with agents affecting QT interval
• Lactose intolerance
• Galactose intolerance e.g. galactosaemia
• Lapp lactase deficiency
• Glucose-galactose malabsorption
• Fructose intolerance
• May impair ability to drive and operate machinery

International manufacturer recommendation

• Pregnancy
• Breastfeeding
• Severe hepatic impairment
• Children and adolescents
• Deterioration of disease
• Acute asthma
• Acute episodes of bronchospasm for which a short-acting bronchodilator is required
• High doses for prolonged periods
• Withdrawal of treatment without medical practitioner supervision
• Cardiovascular disorders
  - Coronary artery disease
  - Acute myocardial infarction
  - Cardiac arrhythmias
  - Hypertension
• Seizure disorders
• Thyrotoxicosis
• Unusual responsiveness to beta₂-adrenergic agonists
• Unstable ischaemic heart disease
• History of myocardial infarction in last 12 months
• New York Heart Association (NYHA) class III/IV left ventricular failure
• Arrhythmia
• Uncontrolled hypertension
• Cerebrovascular disease
• History of long QT syndrome
• Known or suspected prolongation of QT interval
• Pre-existing hypokalaemia
• Hypoxia
• Diabetes
  - Type I diabetes mellitus 
  - Uncontrolled Type II diabetes mellitus 
• Pulmonary tuberculosis
• Chronic or untreated infections
• Abrupt withdrawal
• Coadministration with agents affecting QT interval
• Galactose intolerance 
• Total lactose intolerance
• Glucose-galactose malabsorption

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

Dosages below include:

• South African manufacturer recommendations
• International manufacturer recommendations

South African manufacturer recommendations

Asthma, where use of a combination of a long-acting beta₂-agonist and an inhaled corticosteroid is appropriate
- Maintenance therapy in those not adequately controlled with inhaled corticosteroids and “as needed” inhaled short-acting beta₂-agonists

Indacaterol/ Mometasone Furoate
150/80 (μg)
150/160 (μg) 

• Inhaled (cps): 1 cap, dly

150/320 (μg) 

• Inhaled (cps): 1 cap, dly; Max: 1 inhalation/24hrs

- Maintenance therapy in those not adequately controlled with long-acting beta₂-agonist and low dose of inhaled corticosteroids

Indacaterol/ Mometasone Furoate 
150/160 (μg) 

• Inhaled (cps): 1 cap, dly 

150/320 (μg)

• Inhaled (cps): 1 cap, dly; Max: 1 inhalation/24hrs

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150/80 micrograms once daily recommended in patients who require a combination of a long-acting  beta₂-agonist and a low dose of inhaled corticosteroid. 150/160 micrograms or 150/320 micrograms once daily recommended in patients who require a combination of a long-acting beta₂-agonist and a medium or high dose of inhaled corticosteroid

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For inhalation use only; capsules must not be swallowed. After inhalation, patients should rinse their mouth with water without swallowing

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Patients usually experience an improvement in lung function within 5 minutes of inhaling indacaterol/ mometasone furoate. However, the patient should be informed that regular daily use is necessary to maintain control of asthma symptoms and that use should be continued even when asymptomatic

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If a dose is missed, it should be taken as soon as possible. Patients should be instructed not to take more than one dose in a day

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International manufacturer recommendations

Asthma
- Maintenance therapy in those not adequately controlled with inhaled corticosteroids and inhaled short-acting beta₂-agonists

Indacaterol/ Mometasone Furoate
150/80 (μg)
150/160 (μg)

• Inhaled (cps): 1 cap, dly

150/320 (μg)

• Inhaled (cps): 1 cap, dly; Max: 1 inhalation/24hrs

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Patients should be given the strength containing the appropriate mometasone furoate dosage for the severity of their disease and should be regularly reassessed by a healthcare professional

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For inhalation use only; capsules must not be swallowed. After inhalation, patients should rinse their mouth with water without swallowing

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If a dose is missed, it should be taken as soon as possible. Patients should be instructed not to take more than one dose in a day

Paed. forms avail. and covered in this monograph: cps

Dosages below include:

• South African manufacturer recommendations
• International manufacturer recommendations

South African manufacturer recommendations

Asthma, where use of a combination of a long-acting beta₂-agonist and an inhaled corticosteroid is appropriate
- Maintenance therapy in those not adequately controlled with inhaled corticosteroids and “as needed” inhaled short acting beta₂-agonists 
- Maintenance therapy in those not adequately controlled with long-acting beta₂-agonist and low dose of inhaled corticosteroids (150/160 (ug) and 150/320(ug))

Indacaterol/ Mometasone Furoate 
150/80 (μg) 
150/160 (μg)
150/320 (μg)

• Younger than 12 years: Not established for use
• 12 years and older: See adult dosage

International manufacturer recommendations

Asthma
- Maintenance therapy in those not adequately controlled with inhaled corticosteroids and inhaled short-acting beta₂-agonists

Indacaterol/ Mometasone Furoate
150/80 (μg)
150/160 (μg)
150/320 (μg)

• Younger than 12 years: Not established for use
• 12 years and older: See adult dosage

Pregnancy

South African manufacturer recommendations

• Caution; positive evidence of risk in animal studies
• Safety in pregnancy has not been established
• Indacaterol was not teratogenic in rats or rabbits following subcutaneous administration
• In animal reproduction studies with pregnant mice, rats and rabbits, mometasone furoate was teratogenic and when used, caused increased foetal malformations and decreased foetal survival and growth
• The indacaterol component may inhibit labour due to a relaxant effect on uterine smooth muscle

International manufacturer recommendations

• Caution; positive evidence of risk in animal studies 
• There are insufficient data in pregnant women to determine whether there is a risk
• Indacaterol was not teratogenic in rats and rabbits following subcutaneous administration
• In animal reproduction studies with pregnant mice, rats and rabbits, mometasone furoate caused increased foetal malformations and decreased foetal survival and growth
• Indacaterol may inhibit labour due to a relaxant effect on uterine smooth muscle
• Should only be used during pregnancy if the expected benefit to the patient justifies the potential risk to the foetus

Breastfeeding

South African manufacturer recommendations

• Caution; not recommended 
• Safety in breastfeeding has not been established 
• Both indacaterol and mometasone furoate are excreted in rat’s milk
• Mothers who are breastfeeding should not use indacaterol/mometasone furoate

International manufacturer recommendations

• Caution; not recommended 
• No information available on the presence of indacaterol or mometasone furoate in human milk, on the effects on a breastfed infant, or on the effects on milk production. Other inhaled corticosteroids similar to mometasone furoate are transferred into human milk
• Indacaterol (including its metabolites) and mometasone furoate have been detected in the milk of lactating rats
• A decision must be made whether to discontinue breastfeeding or to discontinue/abstain from therapy, taking into account the benefit of breastfeeding for the child and the benefit of therapy for the woman

Fertility 

• Reproduction studies and other data in animals did not indicate a concern regarding fertility in either males or females

Renal Impairment

• No dose adjustment recommended  

Hepatic Impairment 

• Mild or moderate: No dose adjustment recommended 
• Severe: Caution; no information available 

Elderly

• No dose adjustment recommended 

Drugs in Sport

• Prohibited - At all times

Central Nervous System Disorders

• Headache
  - Tension headache
• Psychological or behavioural effects
  - Psychomotor hyperactivity
  - Sleep disorders
  - Anxiety
  - Depression
  - Aggression (particularly in children)

Cardiovascular Disorders

• Tachycardia
  - Increased heart rate 
  - Sinus tachycardia
  - Supraventricular tachycardia
• Increased blood pressure
• Increased pulse rate
• Electrocardiographic (ECG) changes
  - Flattening of the T wave
  - Prolongation of QT interval
  - ST-segment depression

Respiratory Disorders

• Nasopharyngitis
• Upper respiratory tract infection
• Asthma (exacerbation)
• Oropharyngeal candidiasis
• Oropharyngeal pain
  - Oral pain 
  - Odynophagia
  - Oropharyngeal discomfort
  - Throat irritation
• Dysphonia
• Paradoxical bronchospasm

Gastrointestinal Disorders

• Oral candidiasis

Endocrine and Metabolic Disorders

• Hyperglycaemia
  - Increased blood glucose
• Hypokalaemia
• Cushing's syndrome
• Cushingoid features
• Adrenal suppression
• Growth retardation in children and adolescents
• Decrease in bone mineral density

Musculoskeletal Disorders

• Musculoskeletal pain
  - Back pain
  - Musculoskeletal chest pain
  - Myalgia
  - Neck pain
• Muscle spasms

Skin and Subcutaneous Tissue Disorders

• Rash
  - Drug eruption
  - Erythematous rash
  - Pruritic rash
• Pruritus
  - Eye pruritus
  - Genital pruritus
  - Anal pruritus
  - Nasal pruritus

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity
  - Drug eruption
  - Angioedema
  - Drug hypersensitivity
  - Skin rash
  - Erythematous rash
  - Pruritic rash
  - Urticaria
• Angioedema
  - Allergic oedema
  - Periorbital swelling
  - Swelling of eyelid
  - Difficulties in breathing or swallowing
  - Swelling of the tongue, lips and face
• Candidiasis

Sensory Disorders

• Cataracts
  - Cortical cataract
• Glaucoma
• Visual disturbance
• Blurred vision
• Central serous chorioretinopathy (CSCR)

• QT prolonging agents
• Monoamine oxidase inhibitors
• Tricyclic antidepressants
• Hypokalaemic agents
• Methylxanthine derivatives
• Steroids
• Non-potassium-sparing diuretics
• Beta-adrenergic blockers (See additional prescribing points) 
• Strong CYP3A4 inhibitors
• Ketoconazole
• Itraconazole
• Nelfinavir
• Ritonavir
• Cobicistat
• Long-acting beta₂-adrenergic agonists

• Pulmonary function
  - Forced expiratory volume (FEV₁)
  - Peak flow meter 
• Hypothalamic-pituitary-adrenal axis suppression
• Bone mineral density
• Blood pressure
• Heart rate
• Serum glucose
• Serum potassium
• Hepatic function

Specific cases may require

• Growth (paediatrics patients)
• Ophthalmic examination (chronic users)

Additional observations

• Symptom relief
• Increased use of short-acting beta₂-adrenergic agonists
• Central nervous system (CNS) stimulation
• Signs and symptoms of
  - Oral candidiasis
  - Eosinophilic conditions (including eosinophilic granulomatosis with polyangiitis [formerly known as Churg-Strauss syndrome])
  - Hypersensitivity reactions

Beta-adrenergic blockers

• Beta-adrenergic blockers may weaken or antagonise the effect of beta₂-adrenergic agonists
• Indacaterol/mometasone furoate should not be given together with beta-adrenergic blockers unless there are compelling reasons for their use
• Where required, cardioselective beta-adrenergic blockers should be preferred, although they should be administered with caution

The pharmacological effects of beta₂-adrenoceptor agonists, including indacaterol, are at least in part attributable to increased cyclic-3',5'-adenosine monophosphate (cyclic AMP) levels, which cause relaxation of bronchial smooth muscle. When inhaled, indacaterol acts locally in the lung as a bronchodilator. Indacaterol is a partial agonist at the human beta₂-adrenergic receptor with nanomolar potency. In isolated human bronchus, indacaterol has a rapid onset of action and a long duration of action. Although beta₂-adrenergic receptors are the predominant adrenergic receptors in bronchial smooth muscle and beta₁-receptors are the predominant receptors in the human heart, there are also beta₂-adrenergic receptors in the human heart comprising 10% to 50% of the total adrenergic receptors.

Mometasone furoate is a synthetic corticosteroid with high affinity for glucocorticoid receptors and local anti-inflammatory properties. In vitro, mometasone furoate inhibits the release of leukotrienes from leukocytes of allergic patients. In cell culture, mometasone furoate demonstrated high potency in inhibition of synthesis and release of IL-1, IL-5, IL-6 and TNF-alpha. It is also a potent inhibitor of leukotriene production and of the production of the Th2 cytokines IL-4 and IL-5 from human CD4+ T-cells.

COMBINATION PREPARATIONS

Indacaterol/ Mometasone Furoate

Capsules, lung admin 150μg/80μg

• Bemrist Breezhaler 150/80 (Novartis) originator

Capsules, lung admin 150μg/160μg

• Bemrist Breezhaler 150/160 (Novartis) originator

Capsules, lung admin 150μg/320μg

• Bemrist Breezhaler 150/320 (Novartis) originator