DRUG INTERACTIONS
Combivent Inhalation Aerosol has been used concomitantly with other drugs, including sympathomimetic bronchodilators, methylxanthines and steroids, commonly used in the treatment of COPD, without adverse drug reactions. No formal drug interaction studies have been performed with Combivent Inhalation Aerosol and these or other medications commonly used in the treatment of COPD.
Anticholinergic agents:
Although ipratropium bromide is minimally absorbed into the systemic circulation, there is some potential for an additive interaction with concomitantly used anticholinergic medications. Caution is therefore advised in the co-administration of Combivent Inhalation Aerosol with other anticholinergic-containing drugs.
Beta-adrenergic agents:
Caution is advised in the co-administration of Combivent Inhalation Aerosol and other sympathomimetic agents due to the increased risk of adverse cardiovascular effects.
Beta-receptor blocking agents
and albuterol inhibit the effect of each other. Beta-receptor blocking agents should be used with caution in patients with hyperreactive airways.
Diuretics:
The ECG changes and/or hypokalemia which may result from the administration of non-potassium sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the recommended dose of the beta agonist is exceeded. Although the clinical significance of these effects is not known, caution is advised in the co-administration of beta agonist-containing drugs, such as Combivent Inhalation Aerosol, with non-potassium sparing diuretics.
Monoamine oxidase inhibitors or tricyclic antidepressants:
Combivent Inhalation Aerosol should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants or within two weeks of discontinuation of such agents because the action of albuterol on the cardiovascular system may be potentiated.
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OVERDOSAGE
The effects of overdosage are expected to be related primarily to albuterol sulfate. Acute overdosage with ipratropium bromide is unlikely since ipratropium bromide is not well absorbed systemically after aerosol or oral administration. The oral median lethal dose of ipratropium bromide ranged between 1001 and 2010 mg/kg in mice (approximately 30,000 and 60,000 times the maximum recommended human daily inhalation dose on a mg/m2 basis, respectively); between 1667 and 4000 mg/kg in rats approximately 100,000 and 240,000 times the maximum recommended human daily inhalation dose, respectively, on a mg/m2 basis); and between 400 and 1300 mg/kg (approximately 80,000 and 260,000 times the maximum recommended human daily inhalation dose, respectively, on a mg/m2 basis) in dogs. Whereas the oral median lethal dose of albuterol sulfate in mice and rats was greater than 2,000 mg/kg (approximately 10,000 and 20,000 times the maximum recommended human daily inhalation dose, respectively, on a mg/m2 basis), the inhalational median lethal dose could not be determined. Manifestations of overdosage with albuterol may include anginal pain, hypertension, hypokalemia, tachycardia with rates up to 200 beats per minute and exaggeration of the pharmacologic effects listed in ADVERSE REACTIONS. As with all sympathomimetic aerosol medications, cardiac arrest and even death may be associated with abuse. Dialysis is not appropriate treatment for overdosage of albuterol as an inhalation aerosol; the judicious use of a cardiovascular beta-receptor blocker, such as metoprolol tartrate may be indicated.
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