Special Warning : אזהרת שימוש

4.4       Special warnings and precautions for use

The management of asthma should normally follow a stepwise programme.

Serevent should not be used (and is not sufficient) as the first treatment for asthma.
Serevent is not a replacement for inhaled or oral corticosteroids in asthma (see section 4.1).
Its use is complementary to them. Asthmatic patients must be warned not to stop steroid therapy, and not to reduce it without medical advice, even if they feel better on salmeterol.

Serevent should not be used to treat acute asthma symptoms for which a fast and short- acting inhaled bronchodilator is required. Patients should be advised to have their medicinal product to be used for the relief of acute asthma symptoms available at all times.

Increasing use of bronchodilators, in particular short-acting inhaled β2-agonists, to relieve symptoms, indicates deterioration of asthma control. In this case, the patient should be instructed to seek medical advice.

Although Serevent may be introduced as add-on therapy when inhaled corticosteroids do not provide adequate control of asthma symptoms, patients should not be initiated on Serevent during an acute severe asthma exacerbation, or if they have significantly worsening or acutely deteriorating asthma.

Serious asthma-related adverse events and exacerbations may occur during treatment with Serevent. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation on Serevent.

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 increasing corticosteroid therapy. Under these circumstances daily peak flow monitoring may be advisable. For maintenance treatment of asthma salmeterol should be given in combination with inhaled or oral corticosteroids. Long-acting bronchodilators should not be the only or the main treatment in maintenance asthma therapy (see section 4.1).

Once asthma symptoms are controlled, consideration may be given to gradually reducing the dose of Serevent. Regular review of patients as treatment is stepped down is important. The lowest effective dose of Serevent should be used.

Paradoxical bronchospasm
As with other inhalational therapy paradoxical bronchospasm may occur with an immediate increase in wheezing and fall in peak expiratory flow rate (PEFR) after dosing. This should be treated immediately with a fast-acting inhaled bronchodilator. Serevent Diskus should be discontinued immediately, the patient assessed, and if necessary alternative therapy instituted (see section 4.8).

The pharmacological side effects of beta-2 agonist treatment, such as tremor, subjective palpitations and headache have been reported, but tend to be transient and to reduce with regular therapy (see section 4.8).

Cardiovascular effects
Cardiovascular effects, such as increases in systolic blood pressure and heart rate, may occasionally be seen with all sympathomimetic drugs, especially at higher than therapeutic doses. For this reason, salmeterol should be used with caution in patients with pre-existing cardiovascular disease.

Thyrotoxicosis
Serevent should be administered with caution in patients with thyrotoxicosis.
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Blood glucose levels
There have been very rare reports of increases in blood glucose levels (see section 4.8) and this should be considered when prescribing to patients with a history of diabetes mellitus.

Hypokalaemia
Potentially serious hypokalaemia may result from β2-agonist therapy. Particular caution is advised in acute severe asthma as this effect may be potentiated by hypoxia and by concomitant treatment with xanthine derivatives, steroids and diuretics. Serum potassium levels should be monitored in such situations.

Respiratory-related events
Data from a large clinical trial (the Salmeterol Multi-Center Asthma Research Trial, SMART) suggested African-American patients were at increased risk of serious respiratory- related events or deaths when using salmeterol compared with placebo (see section 5.1). It is not known if this was due to pharmacogenetic or other factors. Patients of black African or Afro-Caribbean ancestry should therefore be asked to continue treatment but to seek medical advice if asthma symptoms remained uncontrolled or worsen whilst using Serevent.

Ketoconazole
Concomitant use of systemic ketoconazole significantly increases systemic exposure to salmeterol. This may lead to an increase in the incidence of systemic effects (e.g.
prolongation in the QTc interval and palpitations). Concomitant treatment with ketoconazole or other potent CYP3A4 inhibitors should therefore be avoided unless the benefits outweigh the potentially increased risk of systemic side effects of salmeterol treatment (see section 4.5).

Inhaler technique
Patients should be instructed in proper use of their inhaler and their technique checked to ensure optimum delivery of the inhaled medicinal product to the lungs.

Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

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