Duo-Medihaler (Isoproterenol Hydrochloride / Phenylephrine Bitartrate Inhalation) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

Drug Interactions: A monoamine oxidase (MAO) inhibitor, a tricyclic antidepressant, or guanethidine may increase the cardiac and pressor effects of phenylephrine and isoproterenol; however, normal volunteers given isoproterenol by inhalation along with an MAO inhibitor or a tricyclic antidepressant had no adverse cardio­vascular effects.

Arrhythmias may result from the concurrent administration of isoproterenol or phenylephrine to patients who are receiving digitalis, epinephrine, cyclopropane, or halogenated hydrocarbon anesthetics.

Beta-adrenergic blocking drugs such as propranolol antagonize the cardiac, bronchodilating, and vasodilating effects of isoproterenol and the stimulating effects of phenylephrine.

Ergot alkaloids may increase blood pressure in patients receiving iso­proterenol or phenylephrine. Phentolamine mesylate (Regitine^®), an alpha-adrenergic blocker, may decrease the pressor response to phenylephrine.

Phenothiazine drugs have some alpha-adrenergic blocking activity and may reduce the pressor effects and duration of action of phenylephrine.

Overdosage

Isoproterenol: The oral LD₅₀ values are as follows: mouse, 1260 mg/kg; rabbit, 3070 mg/kg; male rat, 2230 mg/kg; female rat, 2840 mg/kg; and dog, 600 mg/kg. The intravenous LD₅₀ values are as follows: mouse, 126 mg/kg; rabbit, 27 mg/kg; male rat, 96 mg/kg; female rat, 112 mg/kg; and dog, 50 mg/kg.

Phenylephrine: The oral LD₅₀ values are as follows: rat, 350 mg/kg; and mouse, 120 mg/kg. The intravenous LD₅₀ values are as follows: rat, 6.8 mg/kg; and mouse, 21 mg/kg.

Symptoms: The individual patient's sensitivity to either drug will dictate the overdosage signs. There is reason to believe, however, that the overdosage effects of either drug are antagonized by the other drug in the combination. Severe symptoms of overdosage are more likely to result from parenteral administration of isoproterenol rather than from oral inhalation of isoproterenol and phenylephrine in an aerosol.

Manifestations of acute overdosage include chest pain, dizziness, headache, irregular heartbeat, fast or pounding heartbeat, brady­cardia, nausea or vomiting, restlessness, weakness, flushing, decreased diastolic pressure, convulsions, cerebral hemorrhage, or hypertension.

Treatment: Discontinued dosing allows rapid reversal of adverse effects. Blood pressure and ECG may be monitored and the following treatment used, as appropriate: Tachycardia in asthmatic patients may be treated with cardioselective beta-blockers (meto­prolol or atenolol, but use cautiously since cardioselectivity may not be absolute) and in nonasthmatics with propranolol; brady­cardia may be treated with atropine; blood pressure may be regulated with rapid-acting vasodilators (nitrites, sodium nitro­prusside) or alpha-blocking agents (quinidine, phentolamine). It is not known if isoproterenol or phenylephrine are dialyzable.

Contraindications

DUO-MEDIHALER must not be used by patients with known hyper­sensitivity to sympathomimetics. The use of isoproterenol in patients with pre-existing cardiac arrhythmias associated with tachycardia is contraindicated because the cardiac stimulant effects of the drug may aggravate such disorders.