Bulletin

Levothyroxine Injection

05 November 2009

Products Affected - Description

Levothyroxine sodium lyophilized powder for injection, Bedford Laboratories
200 mcg vial (NDC 55390-0880-10)
500 mcg vial (NDC 55390-0881-10)

Reason for the Shortage

Levothyroxine injection is on a nationwide back order due to increased demand for product.^1,2

Estimated Resupply Dates

Bedford has both the 200 mcg vial and the 500 mcg vial on back order with no release date.¹
APP has available the 200 mcg vial (NDC 63323-0247-10) and 500 mcg vial (NDC 63323-0248-10).²

Implications for Patient Care

Levothyroxine (T₄, tetraiodothyronine) is used for thyroid replacement therapy in patients with hypothyroidism. Injectable levothyroxine may be used in patients needing rapid thyroid replacement (e.g., myxedema coma). Oral levothyroxine is not recommended in patients with myxedema coma due to unpredictable absorption. Levothyroxine is usually preferred over liothyronine (T₃, triiodothyronine) for long-term use.^3-6
Levothyroxine injection is used off-label in brain-dead organ donors to preserve cardiac function prior to organ harvest.^7-9
The Food and Drug Administration (FDA) considers this product to be medically necessary and is working with the manufacturers to ensure ongoing availability.¹⁰
During this shortage, consider using oral levothyroxine products whenever possible. Consider reserving levothyroxine injection for use in patients with myxedema coma and for organ preservation in brain-dead organ donors.

Safety

Use caution when switching between administration routes. The dose of levothyroxine differs significantly by route and by indication.^3,4
Use caution when switching between levothyroxine and liothyronine. Recommended doses differ for these agents.^3-6

Alternative Agents & Management

There are no alternative injectable levothyroxine products.
Liothyronine (T₃, triiodothyronine) injection may be used IV for thyroid replacement therapy, in myxedema coma, or for organ preservation in brain dead organ donors.^5,6,9,11-12 However, liothyronine is usually not preferred for long-term use. Liothyronine has a more rapid onset and shorter duration of action than levothyroxine. Serum T₃ concentrations vary widely during liothyronine therapy, which may increase the risk of serious cardiac adverse effects.^5,6
Table 1 compares the pharmacokinetics of levothyroxine and liothyronine.
Table 2 lists the usual adult dose of levothyroxine and liothyronine for selected indications.

Table 1. Comparison of Levothyroxine and Liothyronine^3-6

Characteristic	Levothyroxine (T₄)	Liothyronine (T₃)
Oral Bioavailability	40-80% (erratic)	95%
Administration Routes	Oral, IV, intramuscular	Oral, IV Do not give intramuscularly or subcutaneously.
Time to Onset of Action	Oral: 3-5 days IV: 6-8 hours	IV: 2-4 hours
Time to Peak Effect	IV: 24 hours	2-3 days
Half-Life	6-7 days	1-2 days

Table 2. Usual Adult Dose of Levothyroxine and Liothyronine for Selected Indications^3-9,11,12

Route/Use	Levothyroxine (T₄)	Liothyronine (T₃)
Oral Administration
Mild Hypothyroidism^3-6	100 mcg/day orally initially, then titrate to response every 6-8 weeks. Maintenance dose usually ranges 100-200 mcg/day. Patients < 50 years with cardiac disease: 25-50 mcg/day orally initially, then titrate by 12.5-25 mcg/day every 6-8 weeks. Patients > 50 years without cardiac disease: 25-50 mcg/day orally initially, then titrate by 12.5-25 mcg/day every 6-8 weeks. Patients > 50 years with cardiac disease: 12.5-25 mcg/day orally initially, then titrate by 12.5-25 mcg/day every 4-8 weeks.	25 mcg/day orally initially, then titrate by 12.5-25 mcg/day every 1-2 weeks (maximum: 100 mcg/day). Maintenance dose usually ranges 25-75 mcg/day. Elderly patients: 5 mcg/day orally initially, then may titrate up by 5 mcg/day every 1-2 weeks. Patients with cardiac disease: 5 mcg/day orally initially, then may titrate up by 5 mcg/day every 1-2 weeks.
Severe Hypothyroidism^3-6	12.5-25 mcg/day orally initially, then titrate by 25 mcg/day every 2-8 weeks. Elderly patients: consider dosage reduction.	5 mcg/day orally initially, then may titrate up by 5-10 mcg/day every 1-2 weeks. Maintenance dose usually ranges 50-100 mcg/day. Elderly patients: consider dosage reduction.
Myxedema Coma^3-6	Not recommended.	5 mcg/day orally initially, then titrate by 5-10 mcg/day every 1-2 weeks. After reaching 25 mcg/day, may titrate by 5-25 mcg/day every 1-2 weeks. Maintenance dose usually ranges 50-100 mcg/day. Elderly patients: consider dosage reduction.
IV Administration
Mild Hypothyroidism^3-6	Give 50% of the oral dose initially. Maintenance dose usually ranges 50-100 mcg IV daily.	No recommendation.
Severe Hypothyroidism^3-6	Give 50% of the oral dose initially. Maintenance dose usually ranges 50-100 mcg IV daily.	No recommendation.
Myxedema Coma^3-6	100-500 mcg IV initially, followed by 100-300 mcg IV the next day if needed. Elderly patients: consider dosage reduction. Patients with cardiac disease: consider dosage reduction.	25-50 mcg IV initially. Wait at least 4 hours, but no more than 12 hours, before giving additional doses. Mortality may improve with administration of at least 65 mcg/day. Patients with known or suspected cardiac disease: 10-20 mcg IV initially. Wait at least 4 hours, but no more than 12 hours, before giving additional doses.
Preserve cardiac function in brain dead organ donors prior to organ harvest^7-9,11,12	20 mcg IV bolus, followed by 10 mcg/hour by continuous IV infusion. Give in combination with methylprednisolone 2 gram IV X1 and insulin 20 units IV X1.	4 mcg IV bolus, followed by 3 mcg/hour by continuous IV infusion. Give in combination with methylprednisolone 15 mg/kg IV X1, vasopressin IV (1 unit bolus, then 0.5-4 unit/hour by continuous IV infusion). May also give insulin 1 unit/hour by continuous IV infusion.

Related Shortages

References

Bedford Laboratories. Customer Service (personal communications). November 30, and December 7, 14, 18, and 20, 2007; and January 14, February 4 and 21, March 19 and 21, April 8, June 24, July 9, August 19, October 1, November 3, December 1, 15, and 23, 2008, January 22, March 2, April 13, May 18, July 13, September 21, and November 3, 2009.
APP (American Pharmaceutical Partners, formerly Abraxis). Customer Service (personal communications). November 30, and December 7, 14, and 18, 2007; and January 14, February 4 and 21, March 6 and 19, April 8, June 24, July 9, August 19, October 1, November 3, December 1, 15, and 23, 2008, January 22, March 2, April 13 and 17, May 18, July 13, September 21, and November 3, 2009.
Levothyroxine sodium. In: AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2007:3242-3245.
Levothyroxine. In: Drug Information Handbook. 15th ed. Hudson, OH: Lexi-Comp Inc; 2007: 1007-1010.
Liothyronine sodium. In: AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists; 2007:3246-3247.
Liothyronine sodium. In: Drug Information Handbook. 15th ed. Hudson, OH: Lexi-Comp Inc; 2007: 1020-1021.
Salim A, Martin M, Brown C, et al. Using thyroid hormone in brain-dead donors to maximize the number of organs available for transplantation. Clin Transplant. 2007;21(3):405-409.
Salim A, Vassiliu P, Velmahos GC, et al. The role of thyroid hormone administration in potential organ donors. Arch Surg. 2001;136(12):1377-1380.
Novitzky D, Cooper DK, Rosendale JD, Kauffman HM. Hormonal therapy of the brain-dead organ donor: experimental and clinical studies. Transplantation. 2006;82(11):1396-1401.
Food and Drug Administration (FDA). Center for Drug Evaluation and Research (CDER) Drug Shortage Program (personal communication). January 17, 2008.
Rosendale JD, Kauffman HM, McBride MA, et al. Aggressive pharmacologic donor management results in more transplanted organs. Transplantation. 2003;75(4):482-487.
Rosendale JD, Kauffman HM, McBride MA, et al. Hormonal resuscitation yields more transplanted hearts, with improved early function. Transplantation. 2003;75(8):1336-1341.

Updated

Updated November 5, 2009 by Leslie Jensen, Pharm.D., Drug Information Specialist. Created December 7, 2007 by M. Christina Beckwith, Pharm.D., Drug Information Specialist. Copyright 2009, Drug Information Service, University of Utah, Salt Lake City, UT.

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