WARNINGS AND PRECAUTIONS SECTION

Highlight: * Cardiac adverse reactions in the elderly and in patients with underlying cardiovascular disease: Initiate levothyroxine sodium tablets at less than the full replacement dose because of the increased risk of cardiac adverse reactions, including atrial fibrillation. (2.3, 5.1, 8.5)

• Myxedema coma: Do not use oral thyroid hormone drug products to treat myxedema coma. (5.2)
• Acute adrenal crisis in patients with concomitant adrenal insufficiency: Treat with replacement glucocorticoids prior to initiation of levothyroxine sodium tablets treatment. (5.3)
• Prevention of hyperthyroidism or incomplete treatment of hypothyroidism: Proper dose titration and careful monitoring is critical to prevent the persistence of hypothyroidism or the development of hyperthyroidism. (5.4)
• Worsening of diabetic control: Therapy in patients with diabetes mellitus may worsen glycemic control and result in increased antidiabetic agent or insulin requirements. Carefully monitor glycemic control after starting, changing, or discontinuing thyroid hormone therapy. (5.5)
• Decreased bone mineral density associated with thyroid hormone over-replacement: Over-replacement can increase bone resorption and decrease bone mineral density. Give the lowest effective dose. (5.6)

5 WARNINGS AND PRECAUTIONS

5.1 Cardiac Adverse Reactions in the Elderly and in Patients with

Underlying Cardiovascular Disease

Over-treatment with levothyroxine may cause an increase in heart rate, cardiac wall thickness, and cardiac contractility and may precipitate angina or arrhythmias, particularly in patients with cardiovascular disease and in elderly patients. Initiate levothyroxine sodium tablets therapy in this population at lower doses than those recommended in younger individuals or in patients without cardiac disease [see Dosage and Administration (2.3), Use in Specific Populations (8.5)].

Monitor for cardiac arrhythmias during surgical procedures in patients with coronary artery disease receiving suppressive levothyroxine sodium tablets therapy. Monitor patients receiving concomitant levothyroxine sodium tablets and sympathomimetic agents for signs and symptoms of coronary insufficiency.

If cardiac symptoms develop or worsen, reduce the levothyroxine sodium tablets dose or withhold for one week and restart at a lower dose.

5.2 Myxedema Coma

Myxedema coma is a life-threatening emergency characterized by poor circulation and hypometabolism, and may result in unpredictable absorption of levothyroxine sodium from the gastrointestinal tract. Use of oral thyroid hormone drug products is not recommended to treat myxedema coma. Administer thyroid hormone products formulated for intravenous administration to treat myxedema coma.

5.3 Acute Adrenal Crisis in Patients with Concomitant Adrenal Insufficiency

Thyroid hormone increases metabolic clearance of glucocorticoids. Initiation of thyroid hormone therapy prior to initiating glucocorticoid therapy may precipitate an acute adrenal crisis in patients with adrenal insufficiency. Treat patients with adrenal insufficiency with replacement glucocorticoids prior to initiating treatment with levothyroxine sodium tablets [see Contraindications (4)].

5.4 Prevention of Hyperthyroidism or Incomplete Treatment of Hypothyroidism

Levothyroxine sodium tablets have a narrow therapeutic index. Over-or undertreatment with levothyroxine sodium tablets may have negative effects on growth and development, cardiovascular function, bone metabolism, reproductive function, cognitive function, emotional state, gastrointestinal function, and glucose and lipid metabolism. Titrate the dose of levothyroxine sodium tablets carefully and monitor response to titration to avoid these effects [see Dosage and Administration (2.4)]. Monitor for the presence of drug or food interactions when using levothyroxine sodium tablets and adjust the dose as necessary [see Drug Interactions (7.9) and Clinical Pharmacology (12.3)].

5.5 Worsening of Diabetic Control

Addition of levothyroxine therapy in patients with diabetes mellitus may worsen glycemic control and result in increased antidiabetic agent or insulin requirements. Carefully monitor glycemic control after starting, changing, or discontinuing levothyroxine sodium tablets [see Drug Interactions (7.2)].

5.6 Decreased Bone Mineral Density Associated with Thyroid Hormone Over-

Replacement

Increased bone resorption and decreased bone mineral density may occur as a result of levothyroxine over-replacement, particularly in post-menopausal women. The increased bone resorption may be associated with increased serum levels and urinary excretion of calcium and phosphorous, elevations in bone alkaline phosphatase, and suppressed serum parathyroid hormone levels. Administer the minimum dose of levothyroxine sodium tablets that achieves the desired clinical and biochemical response to mitigate this risk.

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OVERDOSAGE SECTION

10 OVERDOSAGE

The signs and symptoms of overdosage are those of hyperthyroidism [see Warnings and Precautions (5) and Adverse Reactions (6)]. In addition, confusion and disorientation may occur. Cerebral embolism, shock, coma, and death have been reported. Seizures occurred in a 3-year-old child ingesting 3.6 mg of levothyroxine. Symptoms may not necessarily be evident or may not appear until several days after ingestion of levothyroxine sodium.

Reduce the levothyroxine sodium tablets dose or discontinue temporarily if signs or symptoms of overdosage occur. Initiate appropriate supportive treatment as dictated by the patient’s medical status.

For current information on the management of poisoning or overdosage, contact the National Poison Control Center at 1-800-222-1222 or www.poison.org.

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NONCLINICAL TOXICOLOGY SECTION

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Standard animal studies have not been performed to evaluate the carcinogenic potential, mutagenic potential or effects on fertility of levothyroxine.

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HOW SUPPLIED SECTION

16 HOW SUPPLIED/STORAGE AND HANDLING

Levothyroxine sodium tablets, USP are available containing 25 mcg, 50 mcg, 75 mcg, 88 mcg, 100 mcg, 112 mcg, 125 mcg, 137 mcg, 150 mcg, 175 mcg, 200 mcg or 300 mcg of levothyroxine sodium, USP. They are available as follows:

The 25 mcg tablets are orange color, capsule shaped, biconvex tablets, plain on one side and debossed “score line 1” on the other side.

NDC 31722-284-30 bottles of 30 tablets
NDC 31722-284-90 bottles of 90 tablets
NDC 31722-284-01 bottles of 100 tablets
NDC 31722-284-10 bottles of 1000 tablets

The 50 mcg tablets are white color, capsule shaped, biconvex tablets, plain on one side and debossed “score line 2” on the other side.

NDC 31722-285-30 bottles of 30 tablets
NDC 31722-285-90 bottles of 90 tablets
NDC 31722-285-01 bottles of 100 tablets
NDC 31722-285-10 bottles of 1000 tablets

The 75 mcg tablets are violet color, capsule shaped, biconvex tablets, plain on one side and debossed “score line 3” on the other side.

NDC 31722-286-30 bottles of 30 tablets
NDC 31722-286-90 bottles of 90 tablets
NDC 31722-286-01 bottles of 100 tablets
NDC 31722-286-10 bottles of 1000 tablets

The 88 mcg tablets are olive color, capsule shaped, biconvex tablets, plain on one side and debossed “score line 4” on the other side.

NDC 31722-287-30 bottles of 30 tablets
NDC 31722-287-90 bottles of 90 tablets
NDC 31722-287-01 bottles of 100 tablets
NDC 31722-287-10 bottles of 1000 tablets

The 100 mcg tablets are yellow color, capsule shaped, biconvex tablets, plain on one side and debossed “score line 5” on the other side.

NDC 31722-288-30 bottles of 30 tablets
NDC 31722-288-90 bottles of 90 tablets
NDC 31722-288-01 bottles of 100 tablets
NDC 31722-288-10 bottles of 1000 tablets

The 112 mcg tablets are rose color, capsule shaped, biconvex tablets, plain on one side and debossed “score line 6” on the other side.

NDC 31722-289-30 bottles of 30 tablets
NDC 31722-289-90 bottles of 90 tablets
NDC 31722-289-01 bottles of 100 tablets
NDC 31722-289-10 bottles of 1000 tablets

The 125 mcg tablets are gray color, capsule shaped, biconvex tablets, plain on one side and debossed “score line 7” on the other side.

NDC 31722-290-30 bottles of 30 tablets
NDC 31722-290-90 bottles of 90 tablets
NDC 31722-290-01 bottles of 100 tablets
NDC 31722-290-10 bottles of 1000 tablets

The 137 mcg tablets are turquoise color, capsule shaped, biconvex tablets, plain on one side and debossed “score line 8” on the other side.

NDC 31722-291-30 bottles of 30 tablets
NDC 31722-291-90 bottles of 90 tablets
NDC 31722-291-01 bottles of 100 tablets
NDC 31722-291-10 bottles of 1000 tablets

The 150 mcg tablets are blue color, capsule shaped, biconvex tablets, plain on one side and debossed “score line 9” on the other side.

NDC 31722-292-30 bottles of 30 tablets
NDC 31722-292-90 bottles of 90 tablets
NDC 31722-292-01 bottles of 100 tablets
NDC 31722-292-10 bottles of 1000 tablets

The 175 mcg tablets are lilac color, capsule shaped, biconvex tablets, plain on one side and debossed “1 score line 0” on the other side.

NDC 31722-293-30 bottles of 30 tablets
NDC 31722-293-90 bottles of 90 tablets
NDC 31722-293-01 bottles of 100 tablets
NDC 31722-293-10 bottles of 1000 tablets

The 200 mcg tablets are pink color, capsule shaped, biconvex tablets, plain on one side and debossed “1 score line 1” on the other side.

NDC 31722-294-30 bottles of 30 tablets
NDC 31722-294-90 bottles of 90 tablets
NDC 31722-294-01 bottles of 100 tablets
NDC 31722-294-10 bottles of 1000 tablets

The 300 mcg tablets are green color, capsule shaped, biconvex tablets, plain on one side and debossed “1 score line 2” on the other side.

NDC 31722-295-30 bottles of 30 tablets
NDC 31722-295-90 bottles of 90 tablets
NDC 31722-295-01 bottles of 100 tablets
NDC 31722-295-10 bottles of 1000 tablets

Storage Conditions

Store at USP controlled room temperature 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C and 30°C (59°F to 86°F) [see USP controlled room temperature]. Levothyroxine sodium tablets should be protected from light and moisture.

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