ISOPROTERENOL HYDROCHLORIDE injection, solution

Isoproterenol Hydrochloride by

Drug Labeling and Warnings

Isoproterenol Hydrochloride by is a Prescription medication manufactured, distributed, or labeled by Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc., AVET LIFESCIENCES PRIVATE LIMITED, Emcure Pharmaceuticals Limited. Drug facts, warnings, and ingredients follow.

Drug Details [pdf]

  • 1 INDICATIONS AND USAGE

    Isoproterenol hydrochloride injection is indicated:

    • To improve hemodynamic status in patients in distributive shock and shock due to reduced cardiac output
    • For bronchospasm occurring during anesthesia
  • 2 DOSAGE AND ADMINISTRATION

    2.1 General Considerations

    Inspect visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if the injection is pinkish or darker than slightly yellow or contains a precipitate. Discard any unused portion.

    Diluted solution should be used immediately. Unused material should be discarded.

    2.2 Recommended Dosage

    Dosage should generally be started at the lowest recommended dose and increased gradually based on patient response.

    Recommended dosage for adults with shock and hypoperfusion states:
    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)
    †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. Adjust the rate of infusion based on heart rate, central venous pressure, systemic blood pressure, and urine flow. If the heart rate exceeds 110 beats per minute, consider decreasing or temporarily discontinuing the infusion.
    Recommended dosage for adults with bronchospasm occurring during anesthesia:
    Route of Administration
    Preparation of Dilution
    Initial Dose
    		 Subsequent Dose
    Bolus
    		 Dilute 1 mL (0.2 mg) to 10 mL with
    		 10 mcg to 20 mcg (0.5
    		 The initial dose may be
    intravenous
    injection
    		 Sodium Chloride Injection, USP, or
    5% Dextrose Injection, USP
    		 mL to 1 mL of diluted
    solution)
    		 repeated when necessary

    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.

  • 3 DOSAGE FORMS AND STRENGTHS

    Injection solution: single dose, clear glass vials containing isoproterenol hydrochloride injection, USP is clear colorless to slightly yellow colored solution, free from visible particles.

    • 1 mL containing 0.2 mg/1 mL (0.2 mg/mL)
    • 5 mL containing 1 mg/5 mL (0.2 mg/mL)
  • 4 CONTRAINDICATIONS

    Isoproterenol hydrochloride injection is contraindicated in patients with:

    • tachycardia
    • ventricular arrhythmias
    • angina pectoris
  • 5 WARNINGS AND PRECAUTIONS

    5.1 Cardiac Arrhythmias and Ischemia

    Isoproterenol may induce cardiac arrhythmias and myocardial ischemia in patients, especially patients with coronary artery disease, or cardiomyopathy.

    5.2 Allergic Reactions associated with Sulfite

    Isoproterenol hydrochloride injection contains sodium metabisulfite, which may cause mild to severe allergic reactions including anaphylaxis or asthmatic episodes, particularly in patients with a history of allergies. However, the presence of metabisulfite in this product should not preclude its use for treatment in emergency situations, even if the patient is sulfite-sensitive, as the alternatives to using isoproterenol in a life-threatening situation may not be satisfactory.

  • 6 ADVERSE REACTIONS

    The following adverse reactions have been associated with use of isoproterenol. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure.

    Nervous system disorders: Nervousness, headache, dizziness, visual blurring

    Cardiovascular: Tachycardia, tachyarrhythmias, palpitations, angina, ventricular arrhythmias, Adams-Stokes attacks, pulmonary edema

    Respiratory: Dyspnea

    Other: Flushing of the skin, sweating, mild tremors, pallor, nausea

  • 7 DRUG INTERACTIONS

    Table 1. Clinically Relevant Interactions with Isoproterenol
    Epinephrine
    Clinical Impact
    		 Both drugs are direct cardiac stimulants, and their combined effects
    may induce serious arrhythmias upon simultaneous administration.
    Intervention
    		 Isoproterenol hydrochloride injection and epinephrine should not be administered simultaneously.
    Drugs that may potentiate clinical response of Isoproterenol
    Clinical Impact
    		 The effects of isoproterenol may be potentiated by tricyclic antidepressants, monoamine oxidase inhibitors, levothyroxine sodium, and certain antihistamines, notably chlorpheniramine,
    tripelennamine, and diphenhydramine.
    Intervention
    		 Monitor hemodynamic parameters in patients who concurrently are taking tricyclic antidepressants, monoamine oxidase inhibitors, levothyroxine sodium and certain antihistamines. Adjust doses
    appropriately.
    Drugs that may reduce clinical response of Isoproterenol
    Clinical Impact
    		 The cardiostimulating and bronchodilating effects of
    isoproterenol are antagonized by beta-adrenergic blocking drugs, such as propranolol.
    Intervention
    		 Monitor for hemodynamic response and relief of bronchospasm and
    adjust dose appropriately.
  • 8 USE IN SPECIFIC POPULATIONS

    8.1 Pregnancy

    Risk Summary

    Prolonged experience with isoproterenol use in pregnant women over several decades, based on published literature, do not identify a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. However, there are risks to the mother and fetus associated with isoproterenol use during labor or delivery (see Clinical Considerations).

    The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the United States general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

    Clinical Considerations

    Hypotension associated with shock is a medical emergency in pregnancy which can be fatal if left untreated. Delaying treatment in pregnant women with hypotension associated with shock may increase the risk of maternal and fetal morbidity and mortality. Life-sustaining therapy for the pregnant woman should not be withheld due to potential concerns regarding the effects of isoproterenol on the fetus.

    Labor and Delivery

    Isoproterenol usually inhibits spontaneous or oxytocin induced contractions of the pregnant human uterus and may delay the second stage of labor. Avoid isoproterenol during the second stage of labor. Avoid isoproterenol in obstetrics when maternal blood pressure exceeds 130/80 mmHg.

    Although isoproterenol may improve maternal hypotension associated with shock, it may result in uterine vasoconstriction, decreased uterine blood flow, uterine atony with hemorrhage, and fetal anoxia.

    8.2 Lactation

    Risk Summary

    There is no information regarding the presence of isoproterenol in milk or the effects of isoproterenol on the breastfed infant or on milk production. However, due to its short half-life, isoproterenol exposure is expected to be very low in the breastfed infant.

    8.4 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 to 2.7 µg/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.

    8.5 Geriatric Use

    Clinical studies of isoproterenol hydrochloride injection 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 be cautious, usually starting 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.

  • 10 OVERDOSAGE

    Overdosage of isoproterenol can cause tachycardia or other arrhythmias, palpitations, angina, hypotension, or hypertension. In case of overdosage, reduce the rate of administration or discontinue isoproterenol hydrochloride injection until patient's condition stabilizes. Monitor blood pressure, pulse, respiration, and EKG.

    It is not known whether isoproterenol hydrochloride is dialyzable.

  • 11 DESCRIPTION

    Isoproterenol hydrochloride, USP is 3,4-Dihydroxy-α-[(isopropylamino)methyl] benzyl alcohol hydrochloride, a beta-adrenergic agonist and a synthetic sympathomimetic amine that is structurally related to epinephrine. The molecular formula is C11H17NO3 · HCl. It has a molecular weight of 247.72 and the following structural formula:

    Image

    Isoproterenol hydrochloride is a racemic compound.

    Each milliliter of the sterile solution contains:
    Isoproterenol hydrochloride, USP
    		 0.2 mg
    Edetate Disodium (EDTA)
    		0.2 mg
    Sodium Citrate Dihydrate
    		             2.07 mg
    Citric Acid, Anhydrous
    		               2.5 mg
    Sodium Chloride
    		 7.0 mg
    Water for Injection
    		 qs
    		 1.0 mL

    The pH is adjusted between 2.5 and 3.5 with hydrochloric acid and/or sodium hydroxide. The sterile solution is nonpyrogenic and can be administered by the intravenous route.

  • 12 CLINICAL PHARMACOLOGY

    12.1 Mechanism of Action

    Isoproterenol is a potent nonselective beta-adrenergic agonist with very low affinity for alpha-adrenergic receptors.

    12.2 Pharmacodynamics

    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.

    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.

    12.3 Pharmacokinetics

    Absorption

    Isoproterenol is readily absorbed when given parenterally or as an aerosol.

    Elimination

    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.

  • 13 NONCLINICAL TOXICOLOGY

    13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

    Long-term studies in animals to evaluate the carcinogenic potential of isoproterenol hydrochloride have not been done. Mutagenic potential and effect on fertility have not been determined. There is no evidence from human experience that isoproterenol hydrochloride injection may be carcinogenic or mutagenic or that it impairs fertility.

  • 16 HOW SUPPLIED/STORAGE AND HANDLING

    NDC Fill Concentration Quantity/Container
    23155-660-411 mL0.2 mg/mL10 Single-dose vials (1 mL) in carton
    23155-660-4225 Single-dose vials (1 mL)  in carton
    23155-660-435 Single-dose vials (1 mL)  in carton
    23155-661-415 mL1 mg/5 mL
    (0.2 mg/mL)    		10 Single-dose vials (5 mL) in carton
    23155-661-42 5 Single-dose vials (5 mL) in carton

    Protect from light. Keep in opaque container until used.

    Store at 20° to 25°C (68° to 77°F); excursions permitted between 15° to 30°C (59° to 86°F) [See USP Controlled Room Temperature].

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

    Manufactured by:

    Emcure Pharmaceuticals Ltd.,

    Sanand, Ahmedabad-382110, India.

    Manufactured for:

    Avet Pharmaceuticals Inc.

    East Brunswick, NJ 08816

    1.866.901.DRUG (3784)

    Image

    Revised: 02/2023

  • PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

    NDC: 23155-660-31

    Rx only

    Isoproterenol

     Hydrochloride Injection, USP

    0.2 mg/mL

    Intravenous Use Only.

    Sterile Injection

    1 mL Single Dose Vial

    0.2 mg label

    NDC: 23155-660-41

    Rx only

    Isoproterenol

    Hydrochloride Injection, USP

    0.2 mg/mL

    Intravenous Use Only.

    10 x 1 mL Single Dose Vials

    Sterile Injection

    Discard Unused Portion

    carton 1 ml

    NDC: 23155-660-42

    Rx only

    Isoproterenol

    Hydrochloride Injection, USP

    0.2 mg/mL

    Intravenous Use Only.

    Sterile Injection

    25 x 1 mL Single Dose Vials

    Discard unused portion.

    carton

    NDC: 23155-660-43

    Rx only

    Isoproterenol

    Hydrochloride Injection, USP

    0.2 mg/mL

    Intravenous Use Only.

    Sterile Injection

    5 x 1 mL Single Dose Vials

    Discard unused portion.

    carton

    NDC: 23155-661-31

    Rx only

    Isoproterenol

    Hydrochloride Injection, USP

    1 mg/5 mL

    0.2 mg/mL

    Intravenous Use Only.

    Sterile Injection

    5 mL Single Dose Vial

    label

    NDC: 23155-661-41

    Rx only

    Isoproterenol

    Hydrochloride Injection, USP

    1 mg/5 mL

    0.2 mg/mL

    Intravenous Use Only.

    Sterile Injection

    10 x 5 mL Single Dose Vials

    Discard unused portion.

    carton

    NDC: 23155-661-42

    Rx only

    Isoproterenol

    Hydrochloride Injection, USP

    1 mg/5 mL

    0.2 mg/mL

    Intravenous Use Only.

    Sterile Injection

    5 x 5 mL Single Dose Vials

    Discard unused portion.

    carton
  • INGREDIENTS AND APPEARANCE
    ISOPROTERENOL HYDROCHLORIDE 
    isoproterenol hydrochloride injection, solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 23155-660
    Route of AdministrationINTRAVENOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    ISOPROTERENOL HYDROCHLORIDE (UNII: DIA2A74855) (ISOPROTERENOL - UNII:L628TT009W) ISOPROTERENOL HYDROCHLORIDE0.2 mg  in 1 mL
    Inactive Ingredients
    Ingredient NameStrength
    EDETATE DISODIUM (UNII: 7FLD91C86K) 0.2 mg  in 1 mL
    SODIUM CHLORIDE (UNII: 451W47IQ8X) 7 mg  in 1 mL
    TRISODIUM CITRATE DIHYDRATE (UNII: B22547B95K) 2.07 mg  in 1 mL
    ANHYDROUS CITRIC ACID (UNII: XF417D3PSL) 2.5 mg  in 1 mL
    WATER (UNII: 059QF0KO0R)  
    HYDROCHLORIC ACID (UNII: QTT17582CB)  
    SODIUM HYDROXIDE (UNII: 55X04QC32I)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 23155-660-4110 in 1 CARTON11/19/2021
    1NDC: 23155-660-311 mL in 1 VIAL; Type 0: Not a Combination Product
    2NDC: 23155-660-4225 in 1 CARTON11/19/2021
    2NDC: 23155-660-311 mL in 1 VIAL; Type 0: Not a Combination Product
    3NDC: 23155-660-435 in 1 CARTON11/19/2021
    3NDC: 23155-660-311 mL in 1 VIAL; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA21218911/19/2021
    ISOPROTERENOL HYDROCHLORIDE 
    isoproterenol hydrochloride injection, solution
    Product Information
    Product TypeHUMAN PRESCRIPTION DRUGItem Code (Source)NDC: 23155-661
    Route of AdministrationINTRAVENOUS
    Active Ingredient/Active Moiety
    Ingredient NameBasis of StrengthStrength
    ISOPROTERENOL HYDROCHLORIDE (UNII: DIA2A74855) (ISOPROTERENOL - UNII:L628TT009W) ISOPROTERENOL HYDROCHLORIDE0.2 mg  in 1 mL
    Inactive Ingredients
    Ingredient NameStrength
    EDETATE DISODIUM (UNII: 7FLD91C86K) 0.2 mg  in 1 mL
    SODIUM CHLORIDE (UNII: 451W47IQ8X) 7 mg  in 1 mL
    TRISODIUM CITRATE DIHYDRATE (UNII: B22547B95K) 2.07 mg  in 1 mL
    ANHYDROUS CITRIC ACID (UNII: XF417D3PSL) 2.5 mg  in 1 mL
    WATER (UNII: 059QF0KO0R)  
    HYDROCHLORIC ACID (UNII: QTT17582CB)  
    SODIUM HYDROXIDE (UNII: 55X04QC32I)  
    Packaging
    #Item CodePackage DescriptionMarketing Start DateMarketing End Date
    1NDC: 23155-661-4110 in 1 CARTON11/19/2021
    1NDC: 23155-661-315 mL in 1 VIAL; Type 0: Not a Combination Product
    2NDC: 23155-661-425 in 1 CARTON11/19/2021
    2NDC: 23155-661-315 mL in 1 VIAL; Type 0: Not a Combination Product
    Marketing Information
    Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
    ANDAANDA21218911/19/2021
    Labeler - Heritage Pharmaceuticals Inc. d/b/a Avet Pharmaceuticals Inc. (780779901)
    Registrant - AVET LIFESCIENCES PRIVATE LIMITED (853181664)
    Establishment
    NameAddressID/FEIBusiness Operations
    Emcure Pharmaceuticals Limited675467924ANALYSIS(23155-660, 23155-661) , MANUFACTURE(23155-660, 23155-661) , PACK(23155-660, 23155-661) , LABEL(23155-660, 23155-661)
    • © 2024 FDA.report
    This site is not affiliated with or endorsed by the FDA.