Combivent Disease Interactions

Adrenergic bronchodilators can stimulate cardiovascular beta- 1 and beta- 2 receptors, resulting in adverse effects such as tachycardia, palpitation, peripheral vasodilation, blood pressure changes, and ECG changes (e.g., flattening of the T wave; prolongation of the QT interval; ST segment depression). Direct stimulation of cardiac tissues is mediated by beta- 1 receptors and thus less likely to occur with beta-2-selective agents such as albuterol. However, beta-2-selectivity is not absolute and can be lost with larger doses. High dosages of these agents have been associated with precipitation or aggravation of angina, myocardial ischemia, and cardiac arrhythmias. Therapy with adrenergic bronchodilators should be administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, and/or underlying cardiovascular disorders such as coronary insufficiency, cardiac arrhythmias, or hypertension. The recommended dosages should not be exceeded.

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Adrenergic bronchodilators may cause increases in blood glucose concentrations. These effects are usually transient and slight, but may be significant with dosages higher than those normally recommended. Large doses of IV albuterol (not commercially available in the U.S.) and terbutaline sulfate have been reported to cause exacerbation of preexisting diabetes mellitus and ketoacidosis. Therapy with adrenergic bronchodilators should be administered cautiously in patients with diabetes mellitus. Closer monitoring of blood glucose concentrations may be appropriate. Systemic adverse effects are minimized, but not abolished, by administration of these agents via oral inhalation.

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Adrenergic bronchodilators may cause decreases in serum potassium concentrations, primarily when given by nebulization or intravenous administration. Although this effect is usually transient and does not require supplementation, clinically significant hypokalemia may occur in some patients, with the potential to induce cardiovascular adverse effects. The relevance of these observations to oral or oral aerosol/powder for inhalation therapy is unknown. Therapy with adrenergic bronchodilators should be administered cautiously in patients with or predisposed to hypokalemia.

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Adrenergic bronchodilators may cause CNS stimulation. Therapy with adrenergic bronchodilators should be administered cautiously in patients with seizure disorders. Systemic adverse effects are minimized, but not abolished, by administration of these agents via oral inhalation.

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Aclidinium, ipratropium, umeclidinium, and tiotropium are anticholinergic agents. Although systemic effects are uncommon due to the poor absorption of quaternary ammonium compounds from gastrointestinal and nasal mucosa, worsening of urinary retention or angle-closure glaucoma has been reported. Increased intraocular pressure and precipitation or exacerbation of angle-closure glaucoma may also occur due to inadvertent contact of the eye with aerosolized or nebulized drug. Accordingly, therapy with quaternary ammonium compounds should be administered cautiously in patients with urinary retention/obstruction or angle-closure glaucoma. Measures should be taken whenever possible to minimize ocular exposure to these drugs, such as keeping eyes closed during oral inhalation or use of a mouthpiece rather than face mask during nebulization. Patients should be advised to contact their physician if they experience urinary difficulty (especially in patients with prostatic hyperplasia or bladder neck obstruction); or signs and symptoms of angle-closure glaucoma (e.g., eye pain or discomfort; blurred vision; visual halos; colored images in association with red eyes from conjunctival congestion or corneal edema).

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Cases of supraventricular tachycardia and atrial fibrillation have been reported with the use of inhaled anticholinergic agents in patients with COPD/Asthma. Care and monitoring of cardiac function is recommended when prescribing these agents to patients at risk.

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Ipratropium has not been studied in patients with hepatic or renal insufficiency. Therapy with this agent should be used with caution in these patients.

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Levalbuterol is substantially excreted by the kidney, and the risk of toxic reactions may be greater in patients with impaired renal function. Care should be taken in dose selection in patients with renal impairment and it may be useful to monitor renal function.

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