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Metoprolol Injection

Last Updated: June 29, 2018
Status: Current

Products Affected - Description
    • Metoprolol injection, Baxter (formerly Claris), 1 mg/mL, 5 mL vial, 10 count, NDC 36000-0033-10
    • Metoprolol injection, Hikma, 1 mg/mL, 10 mL vial, 10 count, NDC 00143-9660-10
    • Metoprolol injection, Hikma, 1 mg/mL, 5 mL vial, 25 count, NDC 00143-9873-25
    • Metoprolol injection, Mylan Institutional, 1 mg/mL, 5 mL vial, 10 count, NDC 25021-0303-05
    • Metoprolol injection, Pfizer, 1 mg/mL, 5 mL Carpuject syringe, 3 count, NDC 00409-1778-35
    • Metoprolol injection, Pfizer, 1 mg/mL, 5 mL ampule, 12 count, NDC 00409-2285-05
    • Metoprolol injection, Pfizer, 1 mg/mL, 5 mL vial, 10 count, NDC 00409-1778-05
Reason for the Shortage
    • Alvogen has metoprolol injection available.[1]
    • American Regent has had metoprolol injection on long-term back order for several years.[2]
    • Athenex has metoprolol injection available.[3]
    • Claris did not provide a reason for the shortage.[4]
    • Fresenius Kabi has metoprolol injection on shortage due to increased demand.[5]
    • Mylan Institutional acquired metoprolol injection from Sagent. They discontinued metoprolol injection in March 2018.[6]
    • Pfizer has metoprolol injection on shortage due to manufacturing delays.[7]
    • West-Ward has metoprolol injection available.[8]
Available Products
    • Metoprolol injection, Alvogen, 1 mg/mL, 5 mL vial, 10 count, NDC 47781-0587-17
    • Metoprolol injection, Athenex, 1 mg/mL, 5 mL vial, 10 count, NDC 70860-0300-05
    • Metoprolol injection, Fresenius Kabi, 1 mg/mL, 5 mL vial, 10 count, NDC 63323-0660-05

Estimated Resupply Dates

    • Baxter (formerly Claris) has metoprolol 1 mg/mL 5 mL vials on back order and the company cannot estimate a release date.[4]
    • Pfizer has metoprolol 1 mg/mL 5 mL ampules and 1 mg/mL 5 mL Carpuject syringes on back order and the company estimates a release date of 2019. The 1 mg/mL 5 mL vials are available in limited supply.[7]
    • West-Ward has metoprolol 1 mg/mL 5 mL vials on allocation. The 1 mg/mL 10 mL vials are on back order and the company estimates a release date of July 2018.[8]

Implications for Patient Care

    • Beta-adrenergic blockers act on beta-1 and beta-2 adrenergic receptors to decrease chronotropy and inotropy within the heart (beta-1) and to oppose peripheral vasodilation (beta-2). Beta-1 selective agents (eg, atenolol, metoprolol) act only upon the heart and may be preferred over non-selective agents in asthmatic patients because beta-2 blockade increases airway resistance. Chronic administration reduces heart rate and blood pressure. [9-11]
    • Beta-adrenergic blockers may initially increase peripheral resistance due to unopposed alpha-adrenergic effects. However, peripheral resistance does not increase when starting labetalol, which blocks both beta and alpha-adrenergic receptors.[9-11]
    • Metoprolol injection is labeled to treat early acute myocardial infarction. It is used off-label for the short-term management of hypertension in patients unable to take oral medications, and to treat unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI), and supraventricular tachyarrhythmias.[9-11]

Safety

    • Dosing differs between the individual intravenous beta-adrenergic blockers. Use caution when switching between different agents.

Alternative Agents & Management

    • Table 1 compares the available intravenous beta-adrenergic blockers.
    • Table 2 lists potential alternatives for specific clinical situations. Drugs with different mechanisms of action may be used for certain indications.
    Table 1. Comparison of Intravenous Beta-Adrenergic Blockers9-11
    Agent Receptor antagonist activity Half-life (hours) Lipid solubility Administration
    Esmolol Beta-1 0.15 Low Continuous intravenous infusion.
    Labetalol Alpha-1, Beta-1, Beta-2 5.5 to 8 Moderate Slow intravenous injection or continuous intravenous infusion.
    Metoprolol Beta-1 3 to 7 Moderate Rapid intravenous push, or over 1 or 2 minutes.
    Propranolol Beta-1, Beta-2 2 to 3 High Slow intravenous push, at a maximum rate of 1 mg/min.

    Table 2. Alternatives to Intravenous Beta-Adrenergic Blockers in Specific Clinical Situations9-15
    Situation Alternatives and Dosing Comments
    Acute myocardial infarction, early treatment9-12 Esmolol: Load with 500 mcg/kg intravenous over 1 minute, then infuse 50 mcg/kg/min for 4 minutes. If inadequate response after 5 minutes, continue intravenous infusion at 50 mcg/kg/min, or may increase rate by increments of 50 mcg/kg/min at intervals of > 4 minutes, up to a maximum of 300 mcg/kg/min or until systolic blood pressure is less than 90 mm Hg. Start therapy with an oral beta-adrenergic blocker as soon as possible.

    Metoprolol: 5 mg rapid intravenous push, then repeat dose every 2 to 5 minutes for a total of 3 doses (15 mg total dose). Within 15 minutes of the last intravenous dose, start metoprolol 25 to 50 mg orally every 6 hours for 48 hours, then increase to 100 mg orally twice daily thereafter.
    Consider conserving intravenous beta-adrenergic blockers for those patients most likely to benefit from their use.

    Dilute esmolol to a final concentration of < 10 mg/mL before infusion (ie, 2.5 g/250 mL or 5 g/500 mL).

    Discontinue intravenous beta-adrenergic blockers for heart rate < 50 beats per minute or systolic blood pressure < 90 mm Hg.

    Begin oral therapy only in patients who tolerate intravenous beta-adrenergic blockers.
    Unstable angina or non-ST-segment elevation myocardial infarction in patients at high risk for ischemic events9-14 Esmolol: Load with 500 mcg/kg intravenous over 2 to 3 minutes, then start continuous infusion at 50 mcg/kg/min. Increase infusion rate by 50 mcg/kg/min every 10 to 15 minutes as needed to reach target heart rate, up to a maximum of 300 mcg/kg/min.

    Metoprolol: 5 mg intravenous push over 1 to 2 minutes, then repeat dose every 5 minutes for a total of 3 doses (15 mg total dose). Within 15 minutes of the last intravenous dose, start metoprolol 25 to 50 mg orally every 6 hour for 48 hours, then increase to 100 mg orally twice daily thereafter.

    Propranolol: Give 0.5 to 1 mg intravenous initially. Within 1 to 2 hours of the intravenous loading dose, start propranolol 40 to 80 mg orally every 6 to 8 hours.
    Consider conserving intravenous beta-adrenergic blockers for those patients most likely to benefit from their use.

    Dilute esmolol to a final concentration of < 10 mg/mL before infusion (ie, 2.5 g/250 mL or 5 g/500 mL).

    Target resting heart rate is 50 to 60 beats per minute.

    Discontinue intravenous beta-adrenergic blockers for heart rate < 50 beats per minute or systolic blood pressure < 90 mm Hg.

    Begin oral therapy only in patients who tolerate intravenous beta-adrenergic blockers.
    Hypertensive emergency9-10,15 Enalaprilat: 1.25 to 5 mg slow intravenous push every 6 hours. In patients taking diuretics, give 0.625 mg initially; may increase to 1.25 mg for second dose if needed.

    Esmolol: Load with 500 mcg/kg intravenous over 1 minute, then infuse 50 to 100 mcg/kg/min for 4 minutes. May repeat loading dose or increase infusion rate to a maximum of 300 mcg/kg/min.

    Hydralazine: 10 to 20 mg intravenous or intramuscular. May repeat every 4 to 6 hours as needed. May increase to 40 mg/dose if needed.

    Labetalol: 10 to 20 mg slow intravenous push, then 40 to 80 mg intravenous every 10 minutes as needed to reduce blood pressure, up to a maximum dose of 300 mg. May also give 0.5 to 2 mg/min by continuous intravenous infusion, up to a maximum dose of 300 mg.

    Metoprolol: 1.25 to 5 mg intravenous every 6 to 12 hours.
    In stable patients, the goal is to reduce blood pressure 25% within 1 hour, then further reduce to 160/100 to 160/110 mm Hg in the next 2 to 6 hours.

    The hypotensive effects of intramuscular hydralazine are delayed compared with intravenous administration.

    Hydralazine injection may have unpredictable and prolonged antihypertensive effects.

    Dilute esmolol to a final concentration of < 10 mg/mL before infusion (ie, 2.5 g/250 mL or 5 g/500 mL).

References

    1. Alvogen. Customer Service (personal communications). November 14, 2017; and February 6, 2018.
    2. American Regent (website). November 7, 2017; March 9, and June 27, 2018.
    3. Athenex. Customer Service (personal communications). November 13, 2017; and May 11, 2018.
    4. Claris. Customer Service (personal communications). November 6, 2017; and March 9, 2018.
    5. Fresenius Kabi. Customer Service (personal communications). November 3, December 15 and 22, 2017; February 5, March 9, April 6, May 10 and 25, and June 28, 2018.
    6. Mylan. Customer Service (personal communications). November 6, 2017; and April 11, 2018.
    7. Pfizer. Customer Service (personal communications and website). November 6, December 20, 2017; January 5, February 6, March 9, April 10, May 11 and 25, and June 29, 2018.
    8. West-Ward. Customer Service (personal communications). November 2 and November 30, December 14, 2017; February 7 and 28, April 11, May 9 and 23, and June 27, 2018.
    9. Lexicomp Online, Lexi-Drugs. Hudson, Ohio: Lexi-Comp, Inc.; November 7, 2017.
    10. DRUGDEX System (electronic version). Truven Health Analytics, Greenwood Village, CO. Available at: http://www.micromedexsolutions.com/ (Accessed. November 7, 2017).
    11. Baughman VL, Golembiewski J, Gonzales JP, Alvarez W Jr. Anesthesiology & Critical Care Drug Handbook. 10th ed. Hudson, OH: Lexi-Comp, Inc; 2011.
    12. O'Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2013; 61(4): e78-140.
    13. Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine. J Am Coll Cardiol. Aug 14 2007;50(7):e1-e157.
    14. Wright RS, Anderson JL, Adams CD, Bridges CR, Casey DE Jr, et al; American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. 2011 ACCF/AHA focused update incorporated into the ACC/AHA 2007 Guidelines for the Management of Patients with Unstable Angina/Non-ST-Elevation Myocardial Infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines developed in collaboration with the American Academy of Family Physicians, Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons. J Am Coll Cardiol. 2011;57(19):e215-e367.
    15. James PA, Oparil S, Carter BL, et al. 2014 Evidence-Based Guidelines for the Management of High Blood Pressure in Adults. Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2014; 311 (5): 507-520.

Updated

Updated June 29, 2018 by Michelle Wheeler, PharmD, Drug Information Specialist. Created November 7, 2017 by Michelle Wheeler, PharmD, Drug Information Specialist. Copyright 2018, Drug Information Service, University of Utah, Salt Lake City, UT.

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