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Isoproterenol: Drug information

Isoproterenol: Drug information
(For additional information see "Isoproterenol: Patient drug information" and see "Isoproterenol: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Isuprel [DSC]
Pharmacologic Category
  • Beta1/Beta2 Agonist
Dosing: Adult

Note: Patients may exhibit dose-dependent vasodilation due to unopposed beta2-agonism elicited by isoproterenol.

Bradyarrhythmias, AV nodal block: Continuous IV infusion: Usual range: 2 to 10 mcg/minute; titrate to patient response (AHA [Neumar 2010]).

Cardiogenic shock due to bradycardia (off-label use): Continuous IV infusion: 2 to 20 mcg/minute (AHA [van Diepen 2017]).

Provocation during tilt table testing for syncope (off-label use): Continuous IV infusion: Initial: 1 mcg/minute; increase as necessary based on response; maximum dose: 5 mcg/minute (Benditt 1996; Brignole 2004). Note: Timing of initiation and dose adjustment during test may be institution-specific.

Provocation of ventricular arrhythmias in suspected arrhythmogenic right ventricular cardiomyopathy (off-label use): 45 mcg/minute for 3 minutes (regardless of initial heart rate) followed by evaluation for arrhythmia. Note: Perform test after withdrawing beta-blockers, calcium channel blockers, and other antiarrhythmic agents for at least 5 half-lives (Denis 2014).

Torsade de pointes (refractory) (off-label use): Continuous IV infusion: Usual range: 2 to 10 mcg/minute; titrate to patient response (AHA [Neumar 2010]; AHA/ACC/HRS [Al-Khatib 2017]).

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Pediatric

(For additional information see "Isoproterenol: Pediatric drug information")

Note: Patients may exhibit dose-dependent vasodilation due to unopposed beta2-agonism elicited by isoproterenol.

Bradycardia, severe; AV nodal block: Limited data available: Infants, Children, and Adolescents: Continuous IV infusion: 0.05 to 0.5 mcg/kg/minute; titrate to effect; doses as high as 2 mcg/kg/minute may be needed in some patients (Park 2014); usual adult range: 2 to 10 mcg/minute (AHA [Neumar 2010])

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer’s labeling.

Dosing: Older Adult

Refer to adult dosing.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution, Injection, as hydrochloride:

Isuprel: 0.2 mg/mL (1 mL [DSC], 5 mL [DSC]) [contains disodium edta]

Generic: 0.2 mg/mL (1 mL, 5 mL)

Solution, Injection, as hydrochloride [preservative free]:

Generic: 0.2 mg/mL (1 mL, 5 mL)

Generic Equivalent Available: US

Yes

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Injection, as hydrochloride:

Generic: 0.2 mg/mL (1 mL, 5 mL)

Administration: Adult

IV: IV infusion administration requires the use of an infusion pump.

Administration: Pediatric

Parenteral: Administer by continuous IV infusion; requires the use of an infusion pump

Usual Infusion Concentrations: Adult

IV infusion: 1 mg in 100 mL (10 mcg/mL), 1 mg in 500 mL (2 mcg/mL), or 4 mg in 250 mL (16 mcg/mL) of D5W or NS

Usual Infusion Concentrations: Pediatric

IV infusion: 20 mcg/mL

Use: Labeled Indications

Manufacturer’s labeled indications (see "Note"): Mild or transient episodes of heart block that do not require electric shock or pacemaker therapy; serious episodes of heart block and Adams-Stokes attacks (except when caused by ventricular tachycardia or fibrillation); cardiac arrest until electric shock or pacemaker therapy is available; bronchospasm during anesthesia; adjunct to fluid and electrolyte replacement therapy and other drugs and procedures in the treatment of hypovolemic or septic shock and low cardiac output states (eg, decompensated heart failure, cardiogenic shock)

Note: The use of isoproterenol in advanced cardiac life support (ACLS) has largely been supplanted by the use of other adrenergic agents (eg, epinephrine and dopamine). The use of isoproterenol for bronchospasm during anesthesia and cardiogenic, hypovolemic, or septic shock is no longer recommended. See Off-label Use for more appropriate, yet unlabeled, uses.

Use: Off-Label: Adult

Bradycardia (significant hemodynamic compromise); Cardiogenic shock; Provocation during tilt table testing for syncope; Provocation of ventricular arrhythmias in suspected arrhythmogenic right ventricular cardiomyopathy; Short QT-syndrome and ventricular tachycardia/ventricular fibrillation storm; Torsades de pointes

Medication Safety Issues
Sound-alike/look-alike issues:

Isuprel may be confused with Disophrol, Isordil

High alert medication:

The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drugs which have a heightened risk of causing significant patient harm when used in error.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Frequency not defined.

Cardiovascular: Adams-Stokes syndrome, angina pectoris, flushing, hypertension, hypotension, pallor, palpitations, paradoxical bradycardia (with tilt table testing), tachyarrhythmia, ventricular arrhythmia, ventricular premature contractions

Central nervous system: Dizziness, headache, nervousness, restlessness, seizure (Adams-Stokes)

Dermatologic: Diaphoresis

Endocrine & metabolic: Hypokalemia, increased serum glucose

Gastrointestinal: Nausea, vomiting

Neuromuscular & skeletal: Tremor, weakness

Ophthalmic: Blurred vision

Respiratory: Dyspnea, pulmonary edema

Contraindications

Angina, preexisting ventricular arrhythmias, tachyarrhythmias; cardiac glycoside intoxication

Warnings/Precautions

Disease-related concerns:

• Cardiovascular disease: Use with caution in patients with cardiovascular disease (eg, coronary artery disease); may increase myocardial oxygen demand resulting in ischemia.

• Diabetes: Use with caution in patients with diabetes mellitus; may transiently increase blood glucose levels.

• Distributive shock: Avoid use in patients with distributive shock; may reduce systemic vascular resistance (SVR) further resulting in hemodynamic compromise.

• Hyperthyroidism: Use with caution in patients with hyperthyroidism; may induce thyroid storm in susceptible individuals.

Special populations:

• Elderly: Use with caution in the elderly.

Dosage form specific issues:

• Sulfites: Contains sulfites; may cause allergic reaction in susceptible individuals.

Other warnings/precautions:

• Appropriate use: Use with extreme caution; not currently a treatment of choice. Excessive or prolonged use may result in decreased effectiveness.

Warnings: Additional Pediatric Considerations

Isoproterenol is not recommended for treatment of bronchospasm. In children with refractory asthma, continuous isoproterenol infusion was associated with myocardial necrosis, congestive heart failure, further clinical deterioration, and death in some cases. The risk of cardiac toxicity was observed to be increased by concomitant corticosteroids or methylxanthines, acidosis, or hypoxemia; monitor patients closely (vital signs, ECG, cardiac enzymes) with therapy.

Metabolism/Transport Effects

Substrate of COMT

Drug Interactions

AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Cocaine (Topical): May enhance the hypertensive effect of Sympathomimetics. Management: Consider alternatives to use of this combination when possible. Monitor closely for substantially increased blood pressure or heart rate and for any evidence of myocardial ischemia with concurrent use. Risk D: Consider therapy modification

COMT Inhibitors: May increase the serum concentration of COMT Substrates. Risk C: Monitor therapy

Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Risk C: Monitor therapy

Guanethidine: May enhance the arrhythmogenic effect of Sympathomimetics. Guanethidine may enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy

Inhalational Anesthetics: May enhance the arrhythmogenic effect of Isoproterenol. Risk X: Avoid combination

Kratom: May enhance the adverse/toxic effect of Sympathomimetics. Risk X: Avoid combination

Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Risk D: Consider therapy modification

Ozanimod: May enhance the hypertensive effect of Sympathomimetics. Risk C: Monitor therapy

Solriamfetol: Sympathomimetics may enhance the hypertensive effect of Solriamfetol. Sympathomimetics may enhance the tachycardic effect of Solriamfetol. Risk C: Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy

Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Theophylline Derivatives: Isoproterenol may decrease the serum concentration of Theophylline Derivatives. Risk C: Monitor therapy

Pregnancy Considerations

Animal reproduction studies have not been conducted by the manufacturer. Use of isoproterenol may interfere with uterine contractions at term (Mahon 1967).

Breastfeeding Considerations

It is not known if isoproterenol is present in breast milk. The manufacturer recommends that caution be exercised when administering isoproterenol to breastfeeding women.

Monitoring Parameters

ECG, heart rate, respiratory rate, arterial blood gas, arterial blood pressure, CVP; serum glucose, serum potassium, serum magnesium

Mechanism of Action

Stimulates beta1- and beta2-receptors resulting in relaxation of bronchial, GI, and uterine smooth muscle, increased heart rate and contractility, vasodilation of peripheral vasculature

Pharmacokinetics

Onset of action: IV: Immediate

Duration: IV: 10-15 minutes

Metabolism: Via conjugation in many tissues including hepatic and pulmonary

Half-life elimination: 2.5-5 minutes

Excretion: Urine (primarily as sulfate conjugates)

Pricing: US

Solution (Isoproterenol HCl Injection)

0.2 mg/mL (per mL): $40.80 - $264.00

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Brand Names: International
  • Aleudrina (ES);
  • Antasthmin (AT);
  • Asmadren (NO);
  • Bellasthman Medihaler (DE);
  • Dyspnoesan (NL);
  • Erydin (DK);
  • Euspiran (CZ);
  • Ingelan (AT, DE);
  • Isolin (IN);
  • Isomel (IE);
  • Isomenyl (JP);
  • Isoprenalin (NO, SE);
  • Isoprenalina Cloridrato (IT);
  • Isoprenalinhydrochlorid-Braun (LU);
  • Isuprel (HU, KW, LU);
  • Isuprel HCl (BE, FR, HK, KR, TH);
  • Isuprel Inj (AU, NZ);
  • Isupril (JO);
  • Kattwilon N (DE);
  • Medihaler-Iso (GB, LU, NL, PT);
  • Min-I-Jet Isoprenaline (GB);
  • Novodrin (DE);
  • Proterenal (AR);
  • Proternol L (TW);
  • Saventrine (AE, FI, GB, GR, IE, SG);
  • Sedansol Iso (JP);
  • Sooner (JP)


For country abbreviations used in Lexicomp (show table)

REFERENCES

  1. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS guideline for management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society [published online October 30, 2017]. Circulation. doi: 10.1161/CIR.0000000000000549. [PubMed 29084731]
  2. Almquist A, Goldenberg IF, Milstein S, et al, “Provocation of Bradycardia and Hypotension by Isoproterenol and Upright Posture in Patients With Unexplained Syncope,” N Engl J Med, 1989, 320(6):346-51. [PubMed 2913492]
  3. Benditt DG, Ferguson DW, Grubb BP, et al, “Tilt Table Testing for Assessing Syncope. American College of Cardiology,” J Am Coll Cardiol, 1996, 28(1):263-75. [PubMed 8752825]
  4. Brignole M, Alboni P, Benditt DG, et al, “Guidelines on Management (Diagnosis and Treatment) of Syncope – Update 2004,” Europace, 2004, 6(6):467-537. [PubMed 15519256]
  5. Castilla M, Jerez M, Llácer M, Martinez S. Anaesthetic management in a neonate with congenital complete heart block. Paediatr Anaesth. 2004;14(2):172-175. [PubMed 14962334]
  6. Denis A, Sacher F, Derval N, et al. Diagnostic value of isoproterenol testing in arrhythmogenic right ventricular cardiomyopathy. Circ Arrhythm Electrophysiol. 2014;7(4):590-597. [PubMed 24970294]
  7. Eichenwald EC, Hansen AR, Martin CR, eds. Cloherty and Stark's Manual of Neonatal Care. 8th ed. Lippincott William and Wilkins; 2017.
  8. Field JM, Hazinski MF, Sayre MR, et al, “Part 1: Executive Summary: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care,” Circulation, 2010, 122 (18 Suppl 3):640-56. [PubMed 20956217]
  9. Isoproterenol Hydrochloride [prescribing information]. Vernon Hills, IL: Nexus Pharmaceuticals Inc; April 2017.
  10. Isuprel (isoproterenol) [prescribing information]. Bridgewater, NJ: Valeant Pharmaceuticals North America LLC; August 2016.
  11. Keren A, Tzivoni D, Gavish D, et al, "Etiology, Warning Signs and Therapy of Torsade de Pointes. A Study of 10 Patients," Circulation, 1981, 64(6):1167-74. [PubMed 7296791]
  12. Mahon WA, Reid DW, and Day RA, "The in vivo Effects of Beta Adrenergic Stimulation and Blockade on the Human Uterus at Term," J Pharmacol Exp Ther, 1967, 156(1):178-85. [PubMed 6023594]
  13. Matsubara S, Morimatsu Y, Shiraishi H, et al. Fetus with heart failure due to congenital atrioventricular block treated by maternally administered ritodrine. Arch Gynecol Obstet. 2008;278(1):85-88. [PubMed 18066569]
  14. Morillo CA1, Klein GJ, Zandri S, Yee R. Diagnostic accuracy of a low-dose isoproterenol head-up tilt protocol. Am Heart J. 1995;129(5):901-906. [PubMed 7732979]
  15. Neumar RW, Otto CW, Link MS, et al. Part 8: Adult Advanced Cardiovascular Life Support: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010;122(18 suppl 3):7297-67. doi: 10.1161/CIRCULATIONAHA.110.970988.
  16. Park, MK. Park's Pediatric Cardiology for Practitioners. 6th ed. Philadelphia, PA: Elsevier Health Sciences; 2014.
  17. Passman R, Kadish A. Polymorphic ventricular tachycardia, long Q-T syndrome, and torsades de pointes. Med Clin North Am. 2001;85(2):321-341. [PubMed 11233951]
  18. Sinclair-Pingel J, Grisso AG, Hargrove FR, Wright L. Implementation of standardized concentrations for continuous infusions using a computerized provider Order Entry System [published correction appears in Hosp Pharm. 2007;42:84-85]. Hosp Pharm. 2006;41(11):1102-1106.
  19. van Diepen S, Katz JN, Albert NM, et al; American Heart Association Council on Clinical Cardiology; Council on Cardiovascular and Stroke Nursing; Council on Quality of Care and Outcomes Research; Mission: Lifeline. Contemporary management of cardiogenic shock: a scientific statement from the American Heart Association. Circulation. 2017;136(16):e232-e268. doi:10.1161/CIR.0000000000000525. [PubMed 28923988]
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