Isoproterenol hydrochloride is 3,4-Dihydroxy-α-[(isopropylamino)methyl] benzyl alcohol hydrochloride, a synthetic sympathomimetic amine that is structurally related to epinephrine but acts almost exclusively on beta receptors. The molecular formula is C11H17NO3 • HCl. It has a molecular weight of 247.72 and the following structural formula:

Isoproterenol hydrochloride is a racemic compound.

Isoproterenol hydrochloride, USP is white to practically white crystalline powder and freely soluble in water, soluble in alcohol, less soluble in dehydrated alcohol, insoluble in chloroform and in ether.

Each milliliter of the sterile solution contains:

The sterile solution is nonpyrogenic and can be administered by the intravenous, intramuscular, subcutaneous, or intracardiac routes.

Isoproterenol is a potent nonselective beta-adrenergic agonist with very low affinity for alpha-adrenergic receptors. Intravenous infusion of isoproterenol in man lowers peripheral vascular resistance, primarily in skeletal muscle but also in renal and mesenteric vascular beds. Diastolic pressure falls. Renal blood flow is decreased in normotensive subjects but is increased markedly in shock. Systolic blood pressure may remain unchanged or rise, although mean arterial pressure typically falls. Cardiac output is increased because of the positive inotropic and chronotropic effects of the drug in the face of diminished peripheral vascular resistance. The cardiac effects of isoproterenol may lead to palpitations, sinus tachycardia, and more serious arrhythmias; large doses of isoproterenol may cause myocardial necrosis in animals.

Isoproterenol relaxes almost all varieties of smooth muscle when the tone is high, but this action is most pronounced on bronchial and gastrointestinal smooth muscle. It prevents or relieves bronchoconstriction, but tolerance to this effect develops with overuse of the drug.

In man, isoproterenol causes less hyperglycemia than does epinephrine. Isoproterenol and epinephrine are equally effective in stimulating the release of free fatty acids and energy production.

Absorption, Fate and Excretion
Isoproterenol is metabolized primarily in the liver and other tissues by COMT. Isoproterenol is a relatively poor substrate for MAO and is not taken up by sympathetic neurons to the same extent as are epinephrine and norepinephrine. The duration of action of isoproterenol may therefore be longer than that of epinephrine, but is still brief.

Isoproterenol hydrochloride injection is indicated:

• For mild or transient episodes of heart block that do not require electric shock or pacemaker therapy.
• For serious episodes of heart block and Adams-Stokes attacks (except when caused by ventricular tachycardia or fibrillation) (see CONTRAINDICATIONS).
• For use in cardiac arrest until electric shock or pacemaker therapy, the treatments of choice, is available (see CONTRAINDICATIONS).
• For bronchospasm occurring during anesthesia.
• As an adjunct to fluid and electrolyte replacement therapy and the use of other drugs and procedures in the treatment of hypovolemic and septic shock, low cardiac output (hypoperfusion) states, congestive heart failure, and cardiogenic shock (see WARNINGS).

Use of isoproterenol hydrochloride injection is contraindicated in patients with tachyarrhythmias; tachycardia or heart block caused by digitalis intoxication; ventricular arrhythmias which require inotropic therapy; and angina pectoris.

Isoproterenol hydrochloride 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 hydrochloride injection may produce beneficial hemodynamic and metabolic effects.

In a few patients, presumably with organic disease of the AV node and its branches, isoproterenol hydrochloride injection has paradoxically been reported to worsen heart block or to precipitate Adams- Stokes attacks during normal sinus rhythm or transient heart block.

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 Amneal Biosciences at 1-855-266-3251 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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.

Start isoproterenol hydrochloride 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:

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:

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.

Isoproterenol Hydrochloride Injection, USP is clear, colorless or practically colorless to slightly yellow color liquid. Each mL contains Isoproterenol Hydrochloride USP, 0.2 mg.

It is available as follows:

0.2 mg/mL (1 mL)

1 mL Single-Dose Vial:                                   NDC 70121-1604-1

10 Vials in a Carton:                                       NDC 70121-1604-7

1 mg/5 mL (0.2 mg/mL) (5 mL)

5 mL Single-Dose Vial:                                   NDC 70121-1605-1

10 Vials in a Carton:                                       NDC 70121-1605-7

Store at 20º to 25ºC (68º to 77ºF) [see USP Controlled Room Temperature].

Protect from light. Keep in opaque container until used.

Do not use if the injection is pinkish or darker than slightly yellow or contains a precipitate.

Manufactured by:

Amneal Pharmaceuticals Pvt. Ltd.

Parenteral Unit

Ahmedabad 382213, INDIA

Distributed by:

Amneal Biosciences LLC

Bridgewater, NJ 08807

Rev. 08-2018-00

NDC 70121-1604-1

Isoproterenol Hydrochloride Injection USP, 0.2 mg/mL

Rx only

Vial Label

Amneal Biosciences LLC

NDC 70121-1604-7

Isoproterenol Hydrochloride Injection USP, 0.2 mg/mL

Rx only

Carton Label

Amneal Biosciences LLC

NDC 70121-1605-1

Isoproterenol Hydrochloride Injection USP, 1 mg/ 5 mL

Rx only

Vial Label

Amneal Biosciences LLC

NDC 70121-1605-7

Isoproterenol Hydrochloride Injection USP, 1 mg/ 5 mL

Rx only

Carton Label

Amneal Biosciences LLC