DuoResp Spiromax Special Precautions

Dosing advice: Patients should be reassessed regularly by their prescriber/healthcare provider so that the dose of DuoResp Spiromax remains optimal. The dose should be titrated to the lowest dose at which effective control of symptoms is maintained. Once asthma symptoms are controlled, consideration may be given to gradually reducing the dose of DuoResp Spiromax. When it is appropriate to titrate down to a lower strength than is available for DuoResp Spiromax, a change to an alternative fixed-dose combination of budesonide and formoterol fumarate containing a lower dose of the inhaled corticosteroid is required.
Regular review of patients as treatment is stepped down is important.
Patients should be advised to have their rescue inhaler available at all times, either DuoResp Spiromax (for asthma patients using DuoResp Spiromax as maintenance and reliever therapy) or a separate rapid-acting bronchodilator (for asthma patients using DuoResp Spiromax as maintenance therapy only).
It is recommended that the dose is tapered when the treatment is discontinued and should not be stopped abruptly.
Complete withdrawal of inhaled corticosteroids should not be considered unless it is temporarily required to confirm diagnosis of asthma (for 160/4.5 mcg inhalation powder only).
Patients should be reminded to take their DuoResp Spiromax maintenance dose as prescribed, even when asymptomatic. The prophylactic use of DuoResp Spiromax, e.g. before exercise, has not been studied. The reliever inhalations of DuoResp Spiromax should be taken in response to symptoms but are not intended for regular prophylactic use, e.g. before exercise. In case of frequent need of bronchodilation without corresponding need for an increased dose of inhaled corticosteroids, an alternative reliever should be used.
Deterioration of disease: Serious asthma-related adverse reactions and exacerbations may occur during treatment with DuoResp Spiromax. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation with DuoResp Spiromax.
If patients find the treatment ineffective, or exceed the highest recommended dose of DuoResp Spiromax, medical attention must be sought (see Dosage & Administration). 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.
Patients should not be initiated on DuoResp Spiromax during an exacerbation, or if they have significantly worsening or acutely deteriorating asthma.
Systemic effects: Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long periods. These effects are much less likely to occur with inhalation treatment than with oral corticosteroids.
Possible systemic effects include Cushing's syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children) (see Adverse Reactions).
Visual disturbance: Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.
Effects on bone density: Potential effects on bone density should be considered, particularly in patients on high doses for prolonged periods that have co-existing risk factors for osteoporosis.
Long-term studies with inhaled budesonide in adults at daily doses of 800 micrograms (metered dose) have not shown any significant effects on bone mineral density. No information regarding the effect of a budesonide/formoterol fumarate dihydrate fixed-dose combination at higher doses is available.
Adrenal function: Treatment with supplementary systematic steroids or inhaled budesonide should not be stopped abruptly.
The prolonged treatment with high doses of inhaled corticosteroids, particularly higher than recommended doses, may also result in clinically significant adrenal suppression. Therefore additional systemic corticosteroid cover should be considered during periods of stress such as severe infections or elective surgery. Rapid reduction in the dose of steroids can induce acute adrenal crisis. Symptoms and signs which might be seen in acute adrenal crisis may be somewhat vague but may include anorexia, abdominal pain, weight loss, tiredness, headache, nausea, vomiting, decreased level of consciousness, seizures, hypotension and hypoglycaemia.
Paradoxical bronchospasm: Paradoxical bronchospasm may occur, with an immediate increase in wheezing and shortness of breath, after dosing. If the patient experiences paradoxical bronchospasm DuoResp Spiromax should be discontinued immediately, the patient should be assessed and an alternative therapy instituted, if necessary. Paradoxical bronchospasm responds to a rapid-acting inhaled bronchodilator and should be treated straightaway (see Adverse Reactions).
Transfer from oral therapy: If there is any reason to suppose that adrenal function is impaired from previous systemic steroid therapy, care should be taken when transferring patients to a budesonide/formoterol fumarate fixed-dose combination therapy.
The benefits of inhaled budesonide therapy would normally minimise the need for oral steroids, but patients transferring from oral steroids may remain at risk of impaired adrenal reserve for a considerable time. Recovery may take a considerable amount of time after cessation of oral steroid therapy and hence oral steroid-dependent patients transferred to inhaled budesonide may remain at risk from impaired adrenal function for some considerable time. In such circumstances hypothalamic pituitary adrenocortical (HPA) axis function should be monitored regularly.
During transfer from oral therapy to a budesonide/formoterol fumarate fixed-dose combination therapy, a generally lower systemic steroid action will be experienced which may result in the appearance of allergic or arthritic symptoms such as rhinitis, eczema and muscle and joint pain. Specific treatment should be initiated for these conditions. A general insufficient glucocorticosteroid effect should be suspected if, in rare cases, symptoms such as tiredness, headache, nausea and vomiting should occur. In these cases a temporary increase in the dose of oral glucocorticosteroids is sometimes necessary.
Oral infections: To minimise the risk of oropharyngeal candida infection, the patient should be instructed to rinse their mouth out with water after inhaling the dose. If oropharyngeal thrush occurs, patients should also rinse their mouth with water after the as-needed inhalations (see Dosage & Administration).
COPD population: There are no clinical study data on DuoResp Spiromax available in COPD patients with a pre-bronchodilator FEV₁ >50% predicted normal and with a post-bronchodilator FEV₁ <70% predicted normal (see PHARMACOLOGY: Pharmacodynamics under Actions).
Pneumonia: An increase in the incidence of pneumonia, including pneumonia requiring hospitalisation, has been observed in patients with COPD receiving inhaled corticosteroids. There is some evidence of an increased risk of pneumonia with increasing steroid dose but this has not been demonstrated conclusively across all studies.
There is no conclusive clinical evidence for intra-class differences in the magnitude of the pneumonia risk among inhaled corticosteroid products.
Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of such infections overlap with the symptoms of COPD exacerbations.
Risk factors for pneumonia in patients with COPD include current smoking, older age, low body mass index (BMI) and severe COPD.
Interaction with other medicinal products: Concomitant treatment with itraconazole, ritonavir or other potent CYP3A4 inhibitors should be avoided (see Interactions). If this is not possible the time interval between administrations of the interacting medicinal products should be as long as possible. In patients using potent CYP3A4 inhibitors, a budesonide/formoterol fumarate fixed-dose combination is not recommended.
Caution with special diseases: A fixed-dose combination of budesonide and formoterol fumarate dihydrate should be administered with caution in patients with thyrotoxicosis, phaeochromocytoma, diabetes mellitus, untreated hypokalaemia, hypertrophic obstructive cardiomyopathy, idiopathic subvalvular aortic stenosis, severe hypertension, aneurysm or other severe cardiovascular disorders, such as ischaemic heart disease, tachyarrhythmias or severe heart failure.
Caution should be observed when treating patients with prolongation of the QTc-interval. Formoterol itself may induce prolongation of the QTc-interval.
The need for, and dose of inhaled corticosteroids should be re-evaluated in patients with active or quiescent pulmonary tuberculosis, fungal and viral infections in the airways.
Additional blood glucose controls should be considered in diabetic patients.
β2 adrenoceptor agonists: Potentially serious hypokalaemia may result from high doses of β2 adrenoceptor agonists. Concomitant treatment of β2 adrenoceptor agonists with medicinal products which can induce hypokalaemia or potentiate a hypokalaemic effect, e.g. xanthine-derivatives, steroids and diuretics, may add to a possible hypokalaemic effect of the β2 adrenoceptor agonist.
Treatment with β2 adrenoceptor agonists may result in an increase in blood levels of insulin, free fatty acids, glycerol and ketone bodies.
Particular caution is recommended in unstable asthma with variable use of rescue bronchodilators, in acute severe asthma as the associated risk may be augmented by hypoxia and in other conditions when the likelihood for hypokalaemia is increased. It is recommended that serum potassium levels are monitored during these circumstances.
Excipients: This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
Effects on ability to drive and use machines: DuoResp Spiromax has no or negligible influence on the ability to drive and use machines.
Use in Children: It is recommended that the height of children receiving prolonged treatment with inhaled corticosteroids is regularly monitored. If growth is slowed, therapy should be re-evaluated with the aim of reducing the dose of inhaled corticosteroid to the lowest dose at which effective control of asthma is maintained, if possible. The benefits of the corticosteroid therapy and the possible risks of growth suppression must be carefully weighed. In addition, consideration should be given to referring the patient to a paediatric respiratory specialist.
Limited data from long-term studies suggest that most children and adolescents treated with inhaled budesonide will ultimately achieve their adult target height. However, an initial small but transient reduction in growth (approximately 1 cm) has been observed. This generally occurs within the first year of treatment.