WARNINGS
Fatalities have been reported following excessive use of Alupent® (metaproterenol sulfate USP) as with other sympathomimetic inhalation preparations, and the exact cause is unknown. Cardiac arrest was noted in several cases.
Alupent, like other beta adrenergic agonists, can produce a significant cardiovascular effect in some patients, as measured by pulse rate, blood pressure, symptoms, and/or ECG changes. As with other beta adrenergic aerosols, Alupent can produce paradoxical bronchospasm (which can be life threatening). If it occurs, the preparation should be discontinued immediately and alternative therapy instituted.
Alupent should not be used more often than prescribed. Patients should be advised to contact their physician in the event that they do not respond to their usual dose of a sympathomimetic amine aerosol.
PRECAUTIONS
General
Extreme care must be exercised with respect to the administration of additional sympathomimetic agents.
Since metaproterenol is a sympathomimetic amine, it should be used with caution in patients with cardiovascular disorders, including ischemic heart disease, hypertension or cardiac arrhythmias, in patients with hyperthyroidism or diabetes mellitus, and in patients who are unusually responsive to sympathomimetic amines or who have convulsive disorders. Significant changes in systolic and diastolic blood pressure could be expected to occur in some patients after use of any beta adrenergic bronchodilator.
Information for Patients
Appropriate care should be exercised when considering the administration of additional sympathomimetic agents. A sufficient interval of time should elapse prior to administration of another sympathomimetic agent.
Drug Interactions
Other beta adrenergic aerosol bronchodilators should not be used concomitantly with Alupent® (metaproterenol sulfate USP) because they may have additive effects. Beta adrenergic agonists should be administered with caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, since the action of beta adrenergic agonists on the vascular system may be potentiated.
Carcinogenesis/Mutagenesis/Impairment of Fertility
In an 18-month study in mice, Alupent produced an increase in benign ovarian tumors in females at doses corresponding to 320 and 640 times the maximum recommended dose (based on a 50 kg individual). In a two-year study in rats, a non-significant incidence of benign leiomyomata of the mesovarium was noted at 640 times the maximum recommended dose. The relevance of the findings to man is not known. Mutagenic studies with Alupent have not been conducted. Reproduction studies in rats revealed no evidence of impaired fertility.
Pregnancy
Teratogenic Effects
PREGNANCY CATEGORY C:
Alupent has been shown to be teratogenic and embryotoxic in rabbits when given in doses corresponding to 640 times the maximum recommended dose. These effects included skeletal abnormalities, hydrocephalus and skull bone separation. Results of other studies in rabbits, rats or mice have not revealed any teratogenic, embryocidal or fetotoxic effects. There are no adequate and well-controlled studies in pregnant women. Alupent should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing Mothers
It is not known whether Alupent is excreted in human milk; therefore, Alupent should be used during nursing only if the potential benefit justifies the possible risk to the newborn.
Pediatric Use
Safety and effectiveness in the pediatric population below the age of 12 have not been established. Studies are currently under way in this age group.
|
