Atenolol Injection

03 April 2008

Products Affected - Description

Atenolol 0.5 mg/mL injection (Tenormin), AstraZeneca
10 mL ampul, package of 5 (NDC 00310-0108-10) - discontinued

Esmolol hydrochloride 10 mg/mL injection
10 mL single dose vial, package of 10 (NDC 00574-0862-01), Paddock Laboratories - discontinued

Esmolol hydrochloride 250 mg/mL injection (Brevibloc), Baxter
10 mL ampul (NDC 10019-0025-73) - discontinued
10 mL ampul, package of 10 (NDC 10019-0025-18) - discontinued

Labetalol hydrochloride 5 mg/mL injection, Baxter
20 mL multiple dose vial (NDC 10019-0210-02) - discontinued
40 mL multiple dose vial (NDC 10019-0210-04) - discontinued

Metoprolol tartrate 1 mg/mL injection
5 mL ampul, package of 10 (NDC 00781-3070-95), Sandoz -old NDC, discontinued

Reason for the Shortage

Atenolol

• AstraZeneca has discontinued Tenormin injection.^1,2

Esmolol hydrochloride

• Paddock discontinued esmolol injection in 2007 for undisclosed reasons.³
• Baxter discontinued esmolol 250 ml/mL injection in August 2007 because of the risk of medication errors with this concentration.^{4, 5}
• Bedford did not provide a reason for the shortage.⁶

Labetalol hydrochloride

• Baxter has discontinued labetalol injection.⁵
• Akorn will not give a reason for the shortage.⁷

Metoprolol tartrate

• Bedford, Sandoz, Novartis, and Hospira did not provide a reason for the shortage.^6,8-10

Estimated Resupply Dates

Atenolol

• AstraZeneca has discontinued Tenormin injection.^1,2
• There are no other suppliers of atenolol injection.

Esmolol hydrochloride

• APP (formerly Abraxis) has esmolol 10 mg/mL injection available in 10 mL vials, package of 25 (NDC 63323-0652-10).¹¹
• Baxter has discontinued the Brevibloc 250 mg/mL 10 mL ampul. The company has esmolol 10 mg/mL injection available in 10 mL vials, package of 25 (NDC 00641-2965-45). Baxter also has Brevibloc 10 mg/mL injection available in 10 mL vials, package of 100 (NDC 10019-0115-01) and 250 mL premixed bags (NDC 10019-0055-61). Brevibloc 20 mg/mL injection is available in 5 mL vials, package of 50 (NDC 10019-0085-01) and 100 mL premixed bags (NDC 10019-0075-87).⁵
• Bedford's product is available.⁶

Labetalol hydrochloride

• Apotex has 4 mL single dose vials, package of 10 (NDC 60505-0717-00) available.¹²
• Akorn has 40 mL vials available (NDC 17478-0420-40). The 20 mL vials are on back order with no release date.⁷
• Bedford and Hospira have labetalol injection available in all presentations.^6,9

Metoprolol tartrate

• Bedford currently has 5 mL vials available in packages of 10 (NDC 55390-0073-10).⁶
• Sandoz has 5 mL vials (NDC 00781-3071-95) available.⁸
• Hospira's 5 mL ampuls (NDC 00409-2285-05) and 5 mL Carpuject (NDC 00409-1778-35) are available.⁹
• Novartis has Lopressor 5 mL ampuls available (NDC 00078-0400-01).¹⁰

Propranolol hydrochloride

• Propranolol hydrochloride 1 mg/mL injection is not affected by this shortage.
• APP (formerly Abraxis) has available 1 mL single-dose vials (NDC 63323-0604-01) with short-dating (6 months).¹¹
• Bedford has available 1 mL single dose vials, package of 10 (NDC 55390-0003-10).⁶
• Baxter has Inderal injection available in 1 mL ampuls, package of 10 (NDC 10019-0145-01).⁵

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 (e.g., 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.¹³
• 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.¹³

Atenolol

• Atenolol injection is labeled to treat early acute myocardial infarction. It is also 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.^14-16

Esmolol hydrochloride

• Esmolol injection is labeled to control ventricular rate in supraventricular tachyarrhythmias (eg, atrial fibrillation/flutter, noncompensatory sinus tachycardia), and to treat intraoperative or postoperative tachycardia or hypertension. It is used off-label for the short-term management of hypertension in patients unable to take oral medications, and to treat early acute myocardial infarction, UA, and NSTEMI.^16-18

Labetalol hydrochloride

• Labetalol injection is labeled to treat hypertensive emergency. It is also used off-label for the short-term management of hypertension in patients unable to take oral medications, and to produce controlled hypotension during anesthesia.^15,16,19

Metoprolol tartrate

• 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 UA, NSTEMI, and supraventricular tachyarrhythmias.^15,16,20,21

Propranolol hydrochloride

• Propranolol injection is labeled to treat arrhythmias which are life-threatening or occur during anesthesia, including supraventricular tachyarrhythmias, ventricular tachycardias, tachyarrhythmias associated with digitalis overdose, and resistant tachyarrhythmias associated with catecholamine excess. It is also used off-label to treat UA and NSTEMI.^22-24

Safety

• Dosing differs between the individual IV beta-adrenergic blockers. Use caution when switching between agents.
• Do not administer concentrated esmolol injection. Dilute to less than or equal to 10 mg/mL prior to infusion.¹⁸
• Lamictal (lamotrigine) and labetalol are sound-alike/look-alike drugs. Glaxo-SmithKline, the manufacturer of Lamictal, has reported dispensing errors with these agents.¹⁹

Alternative Agents & Management

• Table 1 compares the available IV beta-adrenergic blockers.
• Table 2 lists potential alternatives for specific clinical situations. Drugs with different mechanisms of action may be used for certain indications.
• IV beta-adrenergic blockers have been included in the primary treatment regimen for early management of UA or NSTEMI.²⁴ These agents decrease myocardial oxygen demand and cardiac workload. Early studies demonstrated significant mortality benefits associated with early use of these agents. The 2007 American College of Cardiology (ACC)/American Heart Association (AHA) UA/NSTEMI guidelines state that there is evidence for net risk with IV beta-adrenergic blockers in hemodynamically unstable patients. In relatively stable patients at low risk for shock, IV beta-adrenergic blockers may provide benefit. Currently, ACC and AHA recommend starting oral beta-adrenergic blockers within 24 hours of presentation in patients with no contraindications to therapy. The guidelines also recommend against IV beta-adrenergic blockers in patients with evidence of a low-output state, increased risk of cardiogenic shock, signs of heart failure, or relative contraindications (active asthma, PR interval > 0.24 seconds, reactive airway disease, or second or third degree heart block).²⁴

Related Shortages

• Esmolol Injection— Resolved
• Labetalol Injection— Resolved
• Metoprolol Injection— Resolved
• Metoprolol Tablets
• Propranolol Long-Acting Capsules— Resolved

References

1. AstraZeneca. Customer Service (personal communication). January 7, 2008.
2. AstraZeneca. Discontinuation of Tenormin injection (written communication). January 24, 2008.
3. Paddock Laboratories. Customer Service (personal communication). January 9, 2008.
4. Medical Affairs. Dear Healthcare Professional Letter. Available on-line at: http://www.fda.gov/downloads/Drugs/DrugSafety/DrugShortages/ucm086036.pdf. Accessed June 24, 2009. New Providence, NJ: Baxter Healthcare Corporation; August 20, 2007.
5. Baxter. Customer Service (personal communications). September 4 and 17, October 11, November 21, and December 11, 2007; and January 9 and 24, February 25, and April 3, 2008.
6. Bedford Laboratories. Customer Service (personal communications). September 4 and 17, October 11, November 2, 6, 12, 21, and 26, and December 4, 13, 17, and 26, 2007; and January 7, 9, 14, 24, and 29, February 11, March 4, 10, and 25, and April 3, 2008.
7. Akorn. Customer Service (personal communications). September 4 and 17, October 11, November 21, and December 11, 2007; and January 7 and 29, 2008.
8. Sandoz. Customer Service (personal communications). November 6, 12, and 21, and December 4, 13, 17, and 26, 2007; and January 7, 14, and 29, February 11, and March 10 and 25, 2008.
9. Hospira. Customer Service (personal communications). September 4 and 17, October 11, November 2 and 21, and December 4, 11, 13, 17, and 26, 2007; and January 7, 11, and 29, February 11, and March 10 and 25, 2008.
10. Novartis. Customer Service (personal communication). January 8 and 29, February 11, and March 4, 10, and 25, 2008.
11. APP Pharmaceuticals (formerly Abraxis Pharmaceutical Products). Customer Service (personal communication). January 9, 10, and 24, February 25, and April 3, 2008.
12. Apotex. Customer Service (personal communications). September 4 and 17, October 11 and 24, November 21, and December 11, 2007; and January 7 and 29, 2008.
13. Beta-adrenergic blocking agents. In: Novak KK, ed. Drug Facts and Comparisons. St. Louis, MO: Wolters Kluwer Health; 2007:467-479b.
14. Atenolol. In: McEvoy GK, ed. AHFS 2007 Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1818-1825.
15. Beta-adrenergic Blocking Agents (Systemic). In: Anon, ed. USP DI Volume 1. Drug Information for the Healthcare Professional. 27th ed. Greenwood Village, CO: Micromedex Thomson Healthcare; 2007:546-563.
16. Lacy CF, Armstrong LL, Goldman MP, Lance LL. Drug Information Handbook. Hudson, OH: Lexi-Comp, Inc; 2007.
17. Esmolol hydrochloride injection. Product information. Bedford, OH: Bedford Laboratories; 2004 June.
18. Esmolol hydrochloride. In: McEvoy GK, ed. AHFS 2007 Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1831-1837.
19. Labetalol hydrochloride. In: McEvoy GK, ed. AHFS 2007 Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1838-1845.
20. Metoprolol succinate, Metoprolol tartrate. In: McEvoy GK, ed. AHFS 2007 Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1845-1854.
21. Lopressor (metoprolol tartrate tablets, USP and metoprolol tartrate injection, USP). Product information. East Hanover, NJ: Novartis Pharmaceuticals Corporation; 2006 May.
22. Propranolol hydrochloride. In: McEvoy GK, ed. AHFS 2007 Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1861-1869.
23. Propranolol hydrochloride injection. Product information. Bedford, OH: Bedford Laboratories; 2006 September.
24. 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.
25. Adrenoreceptor Antagonist Drugs. In: Katzung BG, ed. Basic and Clinical Pharmacology. Stamford, CT: Appleton & Lange; 1998:136-151.
26. Enalaprilat / Enalapril maleate. In: McEvoy GK, ed. AHFS 2007 Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1933-1944.
27. Hydralazine hydrochloride. In: McEvoy GK, ed. AHFS 2007 Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2007:1736-1740.
28. Chobanian AV, Bakris GL, Black HR, et al, National Heart Lung and Blood Institute, National High Blood Pressure Education Program. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. Available at http://www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf. Accessed January 9, 2008. Bethesda, MD: National Institutes of Health; 2004.
29. Donnelly AJ, Baughman VL, Gonzales JP, Tomsik EA. Anesthesiology & Critical Care Drug Handbook. 6th ed. Hudson, OH: Lexi-Comp, Inc; 2005.

Updated

Updated April 3, 2008, by Erin R. Fox, Pharm.D., Drug Information Specialist. Created January 10, 2008, by Thomas M. Sanders, Pharm.D., Drug Information Specialty Resident, and M. Christina Beckwith, PharmD, Drug Information Specialist. Copyright 2008, Drug Information Service, University of Utah, Salt Lake City, UT.

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