Halecord 6 mcg/12 mcg Powder

Asthma

HALECORD 100/6 is indicated in the treatment of asthma in adolescents and adults where use of a combination (inhaled corticosteroid and long-acting beta-2-agonist) is appropriate. HALECORD 200/6 is indicated in the treatment of asthma in adolescents and adults to achieve overall asthma control, including the prevention and relief of symptoms as well as the reduction of the risk of exacerbations. HALECORD is suitable for any asthma severity, where the use of inhaled corticosteroids is appropriate and where a long-acting beta-2-agonist is appropriate.

Chronic obstructive pulmonary disease (COPD)

HALECORD 200/6 is indicated for the regular treatment of patients with moderate to severe chronic obstructive pulmonary disease (COPD), with frequent symptoms and a history of exacerbations.

Posology

The dosage of HALECORD should be individualised according to disease severity. When control has been achieved, the dose should be titrated to the lowest dose at which effective control of symptoms is maintained. HALECORD can be used according to different treatment approaches for asthma:

• HALECORD anti-inflammatory reliever therapy.
• HALECORD anti-inflammatory reliever plus maintenance therapy.
• HALECORD maintenance therapy.

a) HALECORD anti-inflammatory reliever therapy (patients with mild disease): HALECORD 200/6: HALECORD is taken as needed for the relief of asthma symptoms when they occur, and to prevent allergen- or exercise-induced bronchoconstriction (or to prevent symptoms in those circumstances recognised by the patient to precipitate an asthma attack). The formoterol component in HALECORD provides fast onset of effect (within 1-3 minutes) with long-acting (at least 12 hours after a single dose) bronchodilation in reversible airways obstruction. Patients should be advised to always have HALECORD available for relief of symptoms. Clinical studies have demonstrated that HALECORD anti-inflammatory reliever therapy provides significant reductions in severe exacerbations and was statistically superior on daily asthma symptom control compared to a short-acting beta-2-agonist therapy alone.

Recommended doses:

Medical Practitioner should discuss allergen exposure and exercise patterns with the patients and take these into consideration when recommending the dose frequency.

Adults and adolescents (12 years and older): HALECORD 200/6: Patients should take 1 inhalation as needed in response to symptoms and for the prevention of allergen or exercise-induced bronchoconstriction to control asthma. If symptoms persist after a few minutes, an additional inhalation should be taken. Not more than 6 inhalations should be taken on any single occasion. A total daily dose of more than 8 inhalations is normally not needed, however a total daily dose of up to 12 inhalations can be used temporarily. Patients using more than 8 inhalations daily should be reassessed for alternative explanations of persisting symptoms.

b) HALECORD Anti-inflammatory and Reliever Plus Maintenance Therapy: HALECORD 100/6 or HALECORD 200/6: When maintenance treatment with a combination of inhaled corticosteroid and long acting beta-2-agonist is required, HALECORD is taken as anti-inflammatory reliever therapy and in addition, patients take a daily maintenance dose of HALECORD. The as needed inhalations provide both rapid relief of symptoms and improved overall asthma control. Patients should be advised to have HALECORD available for relief of symptoms at all times. A separate inhaler for relief of symptoms is not required.

Clinical studies have demonstrated that HALECORD anti-inflammatory reliever plus maintenance therapy provides clinically meaningful reductions in severe exacerbations while maintaining symptom control, compared to HALECORD maintenance therapy with a separate short-acting bronchodilator.

Recommended doses: Adults and adolescents (12 years and older): HALECORD 100/6: The recommended maintenance dose is 2 inhalations per day, given either as 1 inhalation in the morning and evening or as 2 inhalations in either the morning or the evening. Patients should take 1 additional inhalation as needed in response to symptoms. If symptoms persist after a few minutes, an additional inhalation should be taken. Not more than 6 inhalations should be taken on any single occasion. A reassessment of asthma therapy should be considered in patients using an increasing number of HALECORD inhalations for symptom relief without achieving improved asthma control within 3 days. A total daily dose of more than 8 inhalations is not normally needed, however a total daily dose of up to 12 inhalations could be used temporarily.

If the patient experiences deteriorating symptoms after taking the appropriate maintenance therapy and additional as needed inhalations, the patient should be reassessed for alternative explanations of persisting symptoms.

c) HALECORD Maintenance Therapy (fixed dose): HALECORD 100/6 or HALECORD 200/6: When maintenance treatment with a combination of inhaled corticosteroid and long-acting beta-2-agonist is required, HALECORD is taken as a fixed daily dose treatment, with a separate short-acting bronchodilator for relief of symptoms. Patients should be advised to have their separate short acting bronchodilator available for relief of symptoms at all times. Increasing use of a separate rapid-acting bronchodilator indicates a worsening of the underlying condition and warrants a reassessment of the asthma therapy.

Recommended doses: Adults (18 years and older): HALECORD 100/6 or HALECORD 200/6: 1-2 inhalations twice daily. In some cases, a maximum of up to 4 inhalations twice daily may be required as a maintenance dose or temporarily during worsening of asthma. Adolescents (12-17 years): HALECORD 100/6 or HALECORD 200/6: 1-2 inhalations twice daily. During worsening of asthma, the dose may temporarily be increased to a maximum of 4 inhalations twice daily. When control has been achieved, the dose should be titrated to the lowest dose at which effective control of symptoms is maintained.

COPD Adults (18 years and older): HALECORD 200/6: 2 inhalations twice daily. Maximum daily dose: 4 inhalations.

General information: If patients take HALECORD as a maintenance therapy, they should be instructed that, for optimal benefit, HALECORD must be used even when they are asymptomatic. Special Populations: The patients should be instructed that, for optimal benefit, HALECORD must be used even when they are asymptomatic. There are no special dosing requirements for elderly patients. There are no data available for use of HALECORD in patients with hepatic or renal impairment. As budesonide and formoterol are primarily eliminated via hepatic metabolism, an increased exposure can be expected in patients with severe liver diseases.

• Hypersensitivity to budesonide, formoterol or to inhaled lactose.
• Children below the age of 12 years, as safety and efficacy have not been demonstrated.

Dosing advice

Treatment with HALECORD should not be initiated to treat a severe exacerbation. It is recommended that the dose is tapered when the treatment is discontinued and should not be stopped abruptly. Deterioration of disease

If patients find the treatment ineffective, or exceed the highest recommended dose of HALECORD, medical attention must be sought. Sudden and progressive deterioration in control of asthma or COPD is potentially life threatening and the patient should undergo urgent medical assessment. In this situation consideration should be given to the need for increased therapy with corticosteroids, e.g. a course of oral corticosteroids, or antibiotic treatment if an infection is present. For treatment of severe exacerbations, a combination product of inhaled corticosteroid and long-acting beta-2-agonist alone is not sufficient.

Transfer from oral therapy: Particular care is needed in patients transferring from oral steroids, since they may remain at risk of impaired adrenal function for a considerable time. Patients, who have required high dose emergency corticosteroid therapy or prolonged treatment at the highest recommended dose of inhaled corticosteroids, may also be at risk. These patients may exhibit signs and symptoms of adrenal insufficiency when exposed to severe stress. Additional systemic corticosteroid cover should be considered during periods of stress or elective surgery. In recommended doses HALECORD supplies less than normal physiological amounts of glucocorticosteroid systemically and does NOT provide the mineralocorticosteroid activity that is necessary for coping with these emergencies.

Excipients: Contains lactose. Patients with the rare hereditary conditions of galactose intolerance e.g. galactosaemia, Lapp lactase deficiency, glucose-galactose malabsorption or fructose intolerance should not use HALECORD.

Caution with special diseases: HALECORD should be administered with caution in patients with severe cardiovascular disorders (including heart rhythm abnormalities), diabetes mellitus, untreated hypokalaemia or thyrotoxicosis. High doses of beta-2-agonists can lower serum potassium by inducing a redistribution of potassium from the extracellular to the intracellular compartment, via stimulation of Na+/K+-ATPase in muscle cells. The clinical importance of this effect is uncertain.

COPD Population: Clinical studies and meta-analyses indicate that maintenance treatment of COPD with inhaled corticosteroids may lead to an increased risk of pneumonia. Healthcare professionals should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of pneumonia and exacerbations frequently overlap.

Paediatric population: HALECORD is not indicated in children under 12 years of age.

Pharmacokinetic interactions

The metabolism of budesonide is primarily mediated by the enzyme CYP3A4. Inhibitors of this enzyme, e.g. ketoconazole, may therefore increase systemic exposure to budesonide. This is of limited clinical importance for short-term (1-2 weeks) treatment with ketoconazole but should be taken into consideration during long-term treatment with ketoconazole.

Pharmacodynamic interactions

Beta-adrenergic blockers (including eye drops) can weaken or inhibit the effect of formoterol. Concomitant treatment with quinidine, disopyramide, procainamide, phenothiazines, antihistamines (terfenadine), monoamine oxidase inhibitors and tricyclic antidepressants can prolong the QTc-interval and increase the risk of ventricular dysrhythmias. Budesonide and formoterol have not been observed to interact with any other medicine used in the treatment of asthma.

Pregnancy

For HALECORD or the concomitant treatment with formoterol and budesonide, no clinical data on exposed pregnancies are available. Data from an embryo-foetal developmental study in rats showed no evidence of any additional effect from the combination. There are no adequate data from use of formoterol (as in HALECORD) in pregnant women. In animal reproductive studies formoterol has caused adverse effects in reproduction studies at very high systemic exposure levels (see Preclinical safety data). Data on approximately 2000 exposed pregnancies indicate no increased teratogenic risk associated with the use of inhaled budesonide. In animal studies glucocorticosteroids have been shown to induce malformations (see Preclinical safety data). This is not likely to be relevant for humans given recommended doses. Animal studies have also identified an involvement of excess prenatal glucocorticoids in increased risks for intrauterine growth retardation, adult cardiovascular disease and permanent changes in glucocorticoid receptor density, neurotransmitter turnover and behaviour at exposures below the teratogenic dose range. During pregnancy, HALECORD should only be used when the benefits outweigh the potential risks. The lowest effective dose of budesonide needed to maintain adequate asthma control should be used.

Lactation

Budesonide is excreted in breast milk. However, at therapeutic doses no effects on the suckling child are anticipated. It is not known whether formoterol (as in HALECORD) passes into human breast milk. In rats, small amounts of formoterol have been detected in maternal milk. Administration of HALECORD to women who are breastfeeding should only be considered if the expected benefit to the mother is greater than any possible risk to the child.

Fertility

There is no data available on the potential effect of budesonide on fertility. Animal reproduction studies with formoterol have shown a somewhat reduced fertility in male rats at high systemic exposure.

HALECORD has no or negligible influence on the ability to drive and use machines.

Since HALECORD contains both budesonide and formoterol, the same pattern of undesirable effects as reported for these substances may occur. No increased incidence of adverse reactions has been seen following concurrent administration of the two compounds. The most medicine related adverse reactions are pharmacologically predictable side effects of u03b2 2 -adrenoceptor agonist therapy, such as tremor and palpitations. These tend to be mild and usually disappear within a few days of treatment.

Adverse reactions by frequency and system organ class (SOC)

Frequency System Organ Class Event

Frequent Cardiac disorders: Palpitations Infections and infestations: Candida infections in oropharynx, Pneumonia (in COPD patients) Nervous system disorders: Headache, tremor Respiratory, thoracic and mediastinal disorders: Irritation in the throat, coughing, hoarseness

Less frequent Cardiac disorders: Tachycardia Gastrointestinal disorders: Nausea Musculoskeletal and connective tissue disorders: Muscle cramps Nervous system disorders: Dizziness Psychiatric disorders: Agitation, restlessness, nervousness, sleep disturbances

Less frequent Cardiac disorders: Cardiac dysrhythmias, e.g. atrial fibrillation, supraventricular tachycardia, extrasystoles Immune system disorders: Immediate and delayed hypersensitivity reactions, e.g. dermatitis, exanthema, urticaria, pruritus, angioedema and anaphylactic reaction.

Respiratory, thoracic and mediastinal disorders: Bronchospasm Skin and subcutaneous tissue disorders: Skin bruising

Less frequent Cardiac disorders: Angina pectoris Endocrine disorders: Signs or symptoms of systemic gluco-corticosteroid effects, e.g. hypofunction of the adrenal gland Metabolism and nutrition disorders: Hyperglycaemia Psychiatric disorders: Depression, behavioural disturbances

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are asked to report any suspected adverse reactions to SAHPRA via the u201c6.04 Adverse Drug Reactions Reporting Formu201d, found online under SAHPRAu2019s publications: https://www.sahpra.org.za/Publications/Index/8

Paediatric population Not indicated.

An overdose of formoterol (as in HALECORD) would likely lead to effects that are typical for u03b2 2- adrenoceptor agonists: tremor, headache, palpitations. Symptoms reported from isolated cases are tachycardia, hyperglycaemia, hypokalaemia, prolonged QTc-interval, arrhythmia, nausea, and vomiting. Supportive and symptomatic treatment may be indicated. A dose of 90 micrograms administered during three hours in patients with acute bronchial obstruction raised no safety concerns. Acute overdosage with budesonide, even in excessive doses, is not expected to be a clinical problem. When used chronically in excessive doses, systemic glucocorticosteroid effects, such as hypercorticism and adrenal suppression, may appear.