ATALINE Syrup Ref.[28137] Active ingredients: Terbutaline

As for all beta₂-agonists caution should be observed in patients with thyrotoxicosis.

Cardiovascular effects may be seen with sympathomimetic drugs, including terbutaline. There is some evidence from post-marketing data and published literature of myocardial ischaemia associated with beta agonists.

Patients with underlying severe heart disease (e.g. ischaemic heart disease, arrhythmia or severe heart failure) who are receiving terbutaline should be warned to seek medical advice if they experience chest pain or other symptoms of worsening heart disease. Attention should be paid to assessment of symptoms such as dyspnoea and chest pain, as they may be of either respiratory or cardiac origin.

Due to the hyperglycaemic effects of beta2-agonists, additional blood glucose controls are recommended initially in diabetic patients.

Patients with persistent asthma who require maintenance therapy with beta2-agonists should also receive optimal anti-inflammatory therapy e.g. inhaled corticosteroids, leukotriene receptor antagonists. These patients must be advised to continue taking their anti-inflammatory therapy after the introduction of terbutaline even when symptoms decrease. Should symptoms persist, or if treatment with beta2-agonists needs to be increased, this indicates a worsening of the underlying condition and warrants a reassessment of the therapy. Consideration should be given to the requirements for additional therapy (including increased dosages of anti-inflammatory medication). Severe exacerbations of asthma should be treated as an emergency in the usual manner.

Potentially serious hypokalaemia may result from β₂-agonist therapy. Particular caution is recommended in acute severe asthma as the associated risk may be augmented by hypoxia. The hypokalaemic effect may be potentiated by concomitant treatment with xanthine derivatives, corticosteroids and/or diuretics (see section 4.5). It is recommended that serum potassium levels are monitored in such situations.

Due to the positive inotropic effect of β₂-agonists, these drugs should not be used in patients with hypertrophic cardiomyopathy.

During infusion treatment in pregnant women with β₂-agonists in combination with corticosteroids a rare complication with a pathological picture resembling pulmonary oedema has been reported.

Atalin contains methyl-parahydroxybenzoate and propyl- parahydroxybenzoate, which may cause allergic reactions (possibly delayed), and exceptionally, bronchospasm.

Atalin contains also sorbitol and sucrose.

Patients with rare hereditary problems of fructose intolerance, glucosegalactose malabsorption or sucrase-isomaltase insufficiency should not take this medicine.

Beta-blocking agents (including eye-drops), especially the non-selectiveones such as propranolol, may partially or totally inhibit the effect of β-stimulants. Therefore, terbutaline preparations and non-selective β-blockers should not normally be administered concurrently. Terbutaline should be used with caution in patients receiving other sympathomimetics.

Halogenated anaesthetics

Halothane anaesthesia should be avoided during beta₂-agonists treatment, since it increases the risk of cardiac arrhythmias. Other halogenated anaesthetics should be used cautiously together with beta₂-agonists.

Potassium depleting agents and hypokalaemia

Owing to the hypokalaemic effect of beta-agonists, concurrent administration with terbutaline of serum potassium depleting agents known to exacerbate the risk of hypokalaemia, such as diuretics, methyl xanthines and corticosteroids, should be administered cautiously after careful evaluation of the benefits and risks with special regard to the increased risk of cardiac arrhythmias arising as a result of hypokalaemia (see section 4.4). Hypokalaemia also predisposes to digoxin toxicity.

Pregnancy

Although no teratogenic effects have been observed in animals or in patients, terbutaline should only be administered with caution during the first trimester of pregnancy.

Maintenance treatment with oral beta2-agonists for asthma and other pulmonary diseases should be used with caution at the end of pregnancy because of the potential tocolytic effect.

Breast-feeding

Terbutaline is secreted in breast milk, but effect on the infant is unlikely at therapeutic doses.

Transient hypoglycaemia has been reported in newborn preterm infants after maternal beta2-agonist treatment.

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

Summary of the safety profile

The intensity of the adverse reactions depends on dosage and route of administration. Most of the adverse reactions are characteristic of sympathomimetic amines. The majority of these effects have reversed spontaneously within the first 1-2 weeks of treatment.

The frequency of side-effects is low at the recommended doses.

Tabulated list of adverse reactions

Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (≥1/10), common (≥1/100 to <1/10), uncommon (≥1/1,000 to <1/100), rare (≥1/10,000 to <1/1,000), very rare (<1/10,000) and not known (cannot be estimated from the available data).

^* In rare cases, through unspecified mechanisms, paradoxical bronchospasm may occur, with wheezing immediately after inhalation. This should be immediately treated with a rapid-onset bronchodilator. Terbutaline therapy should be discontinued and after assessment, an alternative therapy initiated.
^** Reported spontaneously in post-marketing data and therefore frequency regarded as unknown.
^*** A few patients feel tense; this is also due to the effects on skeletal muscle and not to direct CNS stimulation.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions to Pharmaceutical Services, Ministry of Health, CY-1475, www.moh.gov.cy/phs, Fax: +357 22608649.

None known.