ORCIPRENALINE Syrup Ref.[10729] Active ingredients: Metaproterenol

Warnings

Like other β2-agonists, ORCIPRENALINE (orciprenaline sulphate) should not be used on a regular daily basis without appropriate concomitant anti-inflammatory therapy (see DOSAGE AND ADMINISTRATION).

ORCIPRENALINE should not be administered to pregnant women or to women of childbearing potential unless in the opinion of the physician the expected benefits outweigh the possible risks to the fetus. In rabbits, high oral doses (100 mg/kg) and low subcutaneous doses (0.2 mg/kg) have resulted in malformed offspring in some experiments, but not in others. Studies in the rat, mouse and rhesus monkey have shown no adverse effects on the developing fetus. Other sympathomimetic drugs tested, viz., ephedrine and phenylephrine, produced teratogenic effects in the rabbit when given orally at high doses as did isoproterenol given subcutaneously at low doses. The significance of these findings is not known.

However, clinical evidence presently available from the use of ORCIPRENALINE in pregnancy is limited. β2-agonists should be used with caution before childbirth in view of their inhibiting effect on uterine contractions.

Care should be taken in patients suffering from myocardial insufficiency, cardiac arrhythmias, recent myocardial infarction, severe organic heart and/or other vascular disorders, hypertension, hyperthyroidism phaeochromocytoma or diabetes mellitus.

Occasional patients have been reported to have developed severe paradoxical airways resistance with repeated excessive use of sympathomimetic inhalation preparations. The cause of this refractory state is unknown. It is advisable that in such instances the use of the preparation be discontinued immediately and alternate therapy instituted since, in the reported cases, the patients did not respond to other forms of therapy until the drug was withdrawn. Fatalities have been reported following excessive use of isoproterenol inhalation preparations and the exact cause is unknown. Cardiac arrest was noted in several instances.

Patients should be advised to seek medical aid in the event that they do not respond to their usual dose of a sympathomimetic amine aerosol. The failure to respond may be due to retention of viscid bronchial secretions, associated with an allergic or infective exacerbation of the patient’s condition. Increased airways resistance on the basis of bronchospasm alone is reversed promptly by bronchodilators and, if this does not occur, a more serious condition should be suspected. Admission to hospital for intensive support of the cardiovascular and respiratory systems may be necessary.

Potentially serious hypokalemia may result from β2–agonist therapy, mainly from parenteral and nebulized administration. Particular caution is advised in acute severe asthma as this may be potentiated by concomitant treatment with xanthine derivatives, steroids and diuretics; the adverse effects of hypokalemia on cardiac rhythm may be exacerbated by hypoxia. It is recommended that serum potassium levels be monitored in such situations. Hypokalemia will increase the susceptibility of digitalis–treated patients to cardiac arrhythmias.

Precautions

If therapy does not produce a significant improvement or if the patient’s condition gets worse, medical advice must be sought in order to determine a new plan of treatment. In the case of acute or rapidly worsening dyspnea, a doctor should be consulted immediately.

Increasing use of β2-agonists to control symptoms of bronchial obstruction, especially administration on a regular basis or in high amounts, indicates deterioration of asthma control. Under these conditions, the patient’s therapy plan has to be revised. It is inadequate simply to increase the use of bronchodilators under these circumstances, in particular over extended periods of time (see DOSAGE AND ADMINISTRATION).

In acute tests, orciprenaline sulphate has been shown to have minimal effect on blood pressure and pulse. The drug should be used with care, however, in asthmatic or emphysematous patients who also have systemic hypertension, coronary artery disease, acute and recurring congestive heart failure, diabetes mellitus, glaucoma or hyperthyroidism or in patients sensitive to sympathomimetic amines.

PREGNANCY

There is no well documented experience in pregnant women. Orciprenaline sulphate should only be used during pregnancy if the potential benefit outweighs the potential risk to the fetus.

LACTATION

It is not known whether orciprenaline sulphate is excreted in human milk; therefore, orciprenaline sulphate should be used during nursing only if the potential benefit justifies the possible risk to the newborn.

In the recommended dosage, the most frequently observed adverse reactions to orciprenaline sulphate include, fine tremor of skeletal muscles, nervousness, headache, dizziness, tachycardia, and palpitations.

As with other beta-mimetics, nausea, vomiting, sweating, weakness and myalgia/muscle cramps may occur. In rare cases decrease in diastolic blood pressure, increase in systolic blood pressure, arrhythmia, particularly after higher doses, may occur.

In rare cases skin reactions or allergic reactions have been reported, especially in hypersensitive patients. There have been isolated cases of anaphylactic or anaphylactoid reactions.

In individual cases psychological alterations have been reported under inhalational therapy with beta-mimetics.

Potentially serious hypokalemia may result from 2-agonist therapy.

As with use of other inhalation therapy, cough, local irritation, and less common, paradoxical bronchoconstriction have been reported.

Concomitant use of orciprenaline sulphate with other sympathomimetic agents is not recommended since the combined use may lead to deleterious cardiovascular effects. If concomitant use is necessary, this should take place only under strict medical supervision.

Extreme care must also be exercised in the concomitant use of orciprenaline sulphate with epinephrine, monoamine oxidase inhibitors or tricyclic antidepressants since the action of beta adrenergic agonists may be enhanced.

Inhalation of halogenated hydrocarbon anaesthetics such as halothane, trichloroethylene and enflurane may increase the susceptibility to the cardiovascular effects of beta-agonists.