Isoproterenol Hydrochloride (Page 2 of 3)

Pediatric Use

Safety and efficacy of isoproterenol in pediatric patients have not been established.

Intravenous infusions of isoproterenol in refractory asthmatic children at rates of 0.05-2.7 mcg/kg/min have caused clinical deterioration, myocardial necrosis, congestive heart failure and death. The risks of cardiac toxicity appear to be increased by some factors [acidosis, hypoxemia, coadministration of corticosteroids, coadministration of methylxanthines (theophylline, theobromine) or aminophylline] that are especially likely to be present in these patients. If I.V. isoproterenol is used in children with refractory asthma, patient monitoring must include continuous assessment of vital signs, frequent electrocardiography, and daily measurements of cardiac enzymes, including CPK-MB.

Geriatric Use

Clinical studies of Isoproterenol Hydrochloride Injection, USP did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects in clinical circumstances. There are, however, some data that suggest that elderly healthy or hypertensive patients are less responsive to beta-adrenergic stimulation than are younger subjects. In general, dose selection for elderly patients should usually start at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant diseases or other drug therapy.

ADVERSE REACTIONS

The following reactions to isoproterenol hydrochloride injection have been reported:

CNS: Nervousness, headache, dizziness, nausea, visual blurring.

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 hydrochloride injection has been reported to precipitate Adams-Stokes seizures during normal sinus rhythm or transient heart block.

Respiratory: Dyspnea.

Other: Flushing of the skin, sweating, mild tremors, weakness, pallor.

To report SUSPECTED ADVERSE REACTIONS, contact Oceanside Pharmaceuticals at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

OVERDOSAGE

The acute toxicity of isoproterenol hydrochloride in animals is much less than that of epinephrine. Excessive doses in animals or man can cause a striking drop in blood pressure, and repeated large doses in animals may result in cardiac enlargement and focal myocarditis.

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 hydrochloride injection until patient’s condition stabilizes. Blood pressure, pulse, respiration, and ECG should be monitored.

It is not known whether isoproterenol hydrochloride is dialyzable.

The oral LD₅₀ of isoproterenol hydrochloride in mice is 3,850 mg/kg ± 1,190 mg/kg of pure drug in solution.

DOSAGE AND ADMINISTRATION

Start Isoproterenol Hydrochloride Injection, USP injection at the lowest recommended dose and increase the rate of administration gradually if necessary while carefully monitoring the patient. The usual route of administration is by intravenous infusion or bolus intravenous injection. In dire emergencies, the drug may be administered by intracardiac injection. If time is not of the utmost importance, initial therapy by intramuscular or subcutaneous injection is preferred.

Recommended dosage for adults with heart block, Adams-Stokes attacks, and cardiac arrest:

* Subsequent dosage and method of administration depend on the ventricular rate and the rapidity with which the cardiac pacemaker can take over when the drug is gradually withdrawn.
Route of Administration	Preparation of Dilution	Initial Dose	Subsequent Dose Range *
Bolus intravenous injection	Dilute 1 mL (0.2 mg) in 9 mL of Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP	0.02 mg to 0.06 mg (1 mL to 3 mL of diluted solution)	0.01 mg to 0.2 mg (0.5 mL to 10 mL of diluted solution)
Intravenous infusion	Dilute 10 mL (2 mg) in 500 mL of 5% Dextrose Injection, USP	5 mcg/min. (1.25 mL of diluted solution per minute)
Intramuscular	Use Solution undiluted	0.2 mg (1 mL)	0.02 mg to 1 mg (0.1 mL to 5 mL)
Subcutaneous	Use Solution undiluted	0.2 mg (1 mL)	0.15 mg to 0.2 mg (0.75 mL to 1 mL)
Intracardiac	Use Solution undiluted	0.02 mg (0.1 mL)

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 mcg/kg/min, with the usual range being 0.1 mcg/kg/min to 1 mcg/kg/min.

Recommended dosage for adults with shock and hypoperfusion states:

* Concentrations up to 10 times greater have been used when limitation of volume is essential. † Rates over 30 mcg per minute have been used in advanced stages of shock. The rate of infusion 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 per minute, it may be advisable to decrease or temporarily discontinue the infusion.
Route of Administration	Preparation of Dilution *	Infusion Rate †
Intravenous infusion	Dilute 5 mL (1 mg) in 500 mL of 5% Dextrose Injection, USP	0.5 mcg to 5 mcg per minute (0.25 mL to 2.5 mL of diluted solution)

Recommended dosage for adults with bronchospasm occurring during anesthesia:

Route of Administration	Preparation of Dilution	Initial Dose	Subsequent Dose
Bolus intravenous injection	Dilute 1 mL (0.2 mg) in 9 mL of Sodium Chloride Injection, USP, or 5% Dextrose Injection, USP	0.01 mg to 0.02 mg (0.5 mL to 1 mL of diluted solution)	The initial dose may be repeated when necessary

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Such solution should not be used.