Indications And Clinical Uses: Inhalation solution: Symptomatic relief of bronchial asthma and in cases of emphysema, bronchitis and other chronic bronchopulmonary disorders in which bronchospasm is a complicating factor.
Injectable form is particularly suitable for the treatment and prevention of (1) Adams-Stokes syndrome and other episodes of heart block, except when caused by ventricular tachycardia or fibrillation (2) cardiac arrest (3) mild or transient episodes of heart block not requiring electric shock or pacemaker therapy (4) laryngobronchospasm during anesthesia (5) as adjunctive therapy in shock.
Contra-Indications: Patients with known hypersensitivity to isoproterenol or any other component of this drug. Patients with tachycardia or heart block caused by digitalis intoxication; ventricular arrhythmias which require inotropic therapy and coronary insufficiency (angina pectoris).
Precautions: Use with caution in patients sensitive to sympathomimetic amines and in the presence of hypertension, cardiovascular disorders (including coronary artery disease and coronary insufficiency), diabetes, hyperthyroidism, in patients with a potential for cardiac arrhythmias and in those patients receiving MAO inhibitors. Potent inhalational anesthetics such as halothane may sensitize the myocardium to effects of sympathomimetic amines.
Occasionally, patients have been reported to develop severe paradoxical airway resistance with repeated, excessive use of aerosol preparations containing sympathomimetic amines. The cause of this refractory state is unknown. It is advisable that in such instances the use of the aerosol be discontinued immediately and alternative therapy instituted, since in the reported cases the patients did not respond to other forms of therapy until the aerosol was withdrawn. Deaths have been reported following excessive use of aerosol preparations containing sympathomimetic amines, the exact cause of which is unknown. Cardiac arrest was noted in several instances.
Isoproterenol injection, by increasing myocardial oxygen requirements while decreasing effective coronary perfusion, may have a deleterious effect on the injured or failing heart. Most experts discourage its use as the initial agent in treating cardiogenic shock following myocardial infarction. However, when a low arterial pressure has been elevated by other means, isoproterenol injection may produce beneficial hemodynamic and metabolic effects.
In a few patients, presumably with organic disease of the AV node and its branches, isoproterenol injection has paradoxically been reported to worsen heart block or to precipitate Adams-Stokes attacks during normal sinus rhythm or transient heart block.
Solution and injection may contain sodium metabisulfite, a sulfite that may cause allergic-type reactions including anaphylactic symptoms and life-threatening or less severe asthmatic episodes in susceptible people. The overall prevalence of sulfite sensitivity in the general population is unknown and probably low. Sulfite sensitivity is seen more frequently in asthmatic than in nonasthmatic people.
Isoproterenol injection should generally be started at the lowest recommended dose. This may be gradually increased, if necessary, while carefully monitoring the patient. Doses sufficient to increase the heart rate to more than 130 beats/minute may increase the likelihood of inducing ventricular arrhythmias. Such increases in heart rate will also tend to increase cardiac work and oxygen requirements which may adversely affect the failing heart or the heart with a significant degree of arteriosclerosis.
Particular caution is necessary in administering isoproterenol injection to patients with coronary artery disease, coronary insufficiency, diabetes, hyperthyroidism and sensitivity to sympathomimetic amines.
Adequate filling of the intravascular compartment by suitable volume expanders is of primary importance in most cases of shock, and should precede the administration of vasoactive drugs. In patients with normal cardiac function, determination of central venous pressure is a reliable guide during volume replacement. If evidence of hypoperfusion persists after adequate volume replacement, isoproterenol injection may be given.
In addition to the routine monitoring of systemic blood pressure, heart rate, urine flow, and the ECG, the response to therapy should also be monitored by frequent determination of the central venous pressure and blood gases. Patients in shock should be closely observed during isoproterenol injection administration. If the heart rate exceeds 110 beats/minute, it may be advisable to decrease the infusion rate or temporarily discontinue the infusion. Determinations of cardiac output and circulation time may also be helpful. Appropriate measures should be taken to ensure adequate ventilation. Careful attention should be paid to acid-base balance and to the correction of electrolyte disturbances. In cases of shock associated with bacteremia, suitable antimicrobial therapy is, of course, imperative.
Drug Interactions: Isoproterenol injection and epinephrine should not be administered simultaneously because both drugs are direct cardiac stimulants and their combined effects may induce serious arrhythmias. The drugs may, however, be administered alternatively provided a proper interval has elapsed between doses.
Isoproterenol should be used with caution, if at all, when potent inhalational anesthetics such as halothane are employed because of potential to sensitize the mycocardium to effects of sympathomimetic amines.
Isoproterenol should not be used with tricyclic antidepressants or MAO inhibitors since the effects of isoproterenol may be magnified.
Pregnancy and Lactation: It is not known whether isoproterenol can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity.
Isoproterenol should be given to a pregnant woman only if clearly needed. It is also not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when isoproterenol is administered to a nursing woman.
Adverse Reactions: The following reactions to isoproterenol injection have been reported: CNS: nervousness, headache, dizziness.
Cardiovascular: tachycardia, palpitations, angina, Adams-Stokes attacks, pulmonary edema, hypertension, hypotension, ventricular arrhythmias, tachyarrhythmias.
In a few patients, presumably with organic disease of the AV node and its branches, isoproterenol injection has been reported to precipitate Adams-Stokes seizures during normal sinus rhythm or transient heart block.
Other: flushing of the skin, sweating, mild tremors, weakness, nausea and vomiting.
Symptoms And Treatment Of Overdose: Symptoms and Treatment: In case of accidental overdosage as evidenced mainly by tachycardia or other arrhythmias, palpitations, angina, hypotension, or hypertension, reduce rate of administration or discontinue isoproterenol injection until patient’s condition stabilizes. Blood pressure, pulse, respiration, and ECG should be monitored.
It is not known whether isoproterenol is dialyzable.
Dosage And Administration: Parenteral: Isoproterenol injection 1:5 000 should generally be started at the lowest recommended dose and the rate of administration gradually increased if necessary while carefully monitoring the patient. The usual route of administration is by i.v. infusion or bolus injection. In dire emergencies, the drug may be administered by intracardiac injection. If time is not of the utmost importance, initial therapy by i.m. or s.c. injection is preferred.
There are no well-controlled studies in children to establish appropriate dosing; however, the American Heart Association recommends an initial infusion rate of 0.1 µg/kg/minute, with the usual range being 0.1Âµg/kg/minute to 1.0 µg/kg/minute.
Cardiac disorders: s.c. or i.m. injection of 200 µg (1 mL of 1:5 000 solution), i.v. injection of 20 to 60 µg (1 to 3 mL of 1:50 000 solution). I.V. infusion of solution containing 1 mg in 250 mL of 5% glucose at a rate of 1.25 mL (5 µg) per minute. Intracardiac injection of 200 µg (1 mL of 1:5 000 solution). Laryngobronchospasm: i.v. injection of from 10 to 20 µg (0.5 to 1 mL of 1:50 000 solution). To prepare 1:50 000 solution dilute 1 mL of 1:5 000 solution to 10 mL with 5% dextrose in water or sodium chloride injection, USP. Adjunctive therapy in shock: i.v. infusion of 1 mg in 500 mL of 5% dextrose in water administered at a rate of 0.5 µg to 5 µg/minute. Infusion rate (up to 30 µg/minute in advanced shock) should be adjusted on the basis of heart rate, central venous pressure, systemic blood pressure and urine flow. If the heart rate exceeds 110 beats/minute, it may be advisable to decrease the infusion rate or temporarily discontinue the infusion.
Solution: Do not use if a precipitate or pinkish to brownish discoloration is observed. Nebulizer solutions should be freshly prepared daily. Isuprel 1:200 solution may be administered by hand nebulizer, compressed air or oxygen operated nebulizer, or by intermittent positive pressure breathing (IPPB) devices.
Acute bronchial asthma: Hand Nebulizer: Depending on the frequency of treatment and the type of nebulizer used, place a volume of Isuprel solution, sufficient for not more than 1 day’s treatment, in the nebulizer using the dropper provided. In time, the patient can learn to adjust the volume required. For adults and children, administer the 1:200 solution by hand bulb nebulization in a dosage of 5 to 15 deep inhalations (using an all glass or plastic nebulizer). If after 5 to 10 minutes inadequate relief is observed, these doses may be repeated once more. If the acute attack recurs, treatments may be repeated up to 5 times daily if necessary. Close patient monitoring is necessary (see Precautions).
Bronchospasm in chronic obstructive lung disease: hand bulb nebulizer: Isuprel 1:200 aerosol solution may be administered daily at not less than 3- to 4-hour intervals for subacute bronchospastic attacks as part of a programmed treatment regimen in patients with chronic obstructive lung disease with a reversible bronchospastic component. An adequate dose is usually 5 to 15 deep inhalations.
Nebulization of compressed air or oxygen: A method often used in patients with severe chronic obstructive lung disease is to deliver the Isuprel mist in more dilute form over a longer period of time. The purpose is, not so much to increase the dose supplied, as to achieve progressively deeper bronchodilatation and thus insure that the mist achieves maximum penetration of the finer bronchioles. Dilute 0.5 mL of Isuprel 1:200 solution to 2 to 2.5 mL with water or isotonic saline to achieve a use concentration of 1:800 to 1:1 000 for this method. The diluted solution is then placed in a nebulizer connected to either a source of compressed air or oxygen. Regulate the flow rate to suit the particular nebulizer so that the diluted isoproterenol solution will be delivered over approximately 10 to 20 minutes. A treatment may be repeated up to 5 times daily if necessary. Although the total delivered dose of Isuprel is somewhat higher than with treatment regimens employing the hand bulb nebulizer, patients usually tolerate it well because of the greater dilution and longer application time factors.
Intermittent Positive Pressure Breathing (IPPB): Diluted solutions of isoproterenol 1:200 are used in a programmed regimen for the treatment of reversible bronchospasm in patients with chronic obstructive lung disease who require IPPB therapy. These devices generally have a small nebulizer, usually of 3 to 5 mL capacity, on a patient operated side arm. The effectiveness of IPPB therapy is greatly enhanced by the simultaneous use of aerosolized bronchodilators. As with compressed air or oxygen operated nebulizers, the usual regimen is to place 0.5 mL of Isuprel 1:200 solution diluted to 2 to 2.5 mL with water or isotonic saline in the nebulizer cup and follow the IPPB manufacturer’s operating instructions. IPPB bronchodilator treatments are usually administered over 15 to 20 minutes, up to 5 times daily if necessary.
Children’s dosage: In general, the technique of Isuprel aerosol solution administration to children is similar to that of adults, since children’s smaller ventilatory exchange capacity automatically provides proportionally smaller aerosol intake. Generally, the 1:200 solution should be used for an acute attack of bronchospasm, and no more than 0.25 mL of the 1:200 solution should be used for each 10 to 15 minute programmed treatment in chronic bronchospastic disease.
Availability And Storage: Ampuls: Each mL of injectable solution contains: isoproterenol HCl 1:5 000. Nonmedicinal ingredients: lactic acid, sodium chloride, sodium lactate and sodium metabisulfite in water for injection. Ampuls of 1 mL, boxes of 5. Ampuls of 5 mL, boxes of 10.
Solution: Each mL of inhalation solution contains: isoproterenol HCl 1:200. (Each 6 drops is equivalent to 0.25 mL.) Nonmedicinal ingredients: citric acid, chlorobutanol, glycerin, sodium chloride and sodium metabisulfite in purified water. Bottles of 10 mL.
ISUPREL® Sanofi Isoproterenol HCl Sympathomimetic