LIOTHYRONINE SODIUM tablet
For Healthcare Providers >

Patient Information

Dosing and Administration

• Instruct patients that liothyronine sodium should only be taken as directed by their healthcare provider.
• Instruct patients to notify their healthcare provider should they become pregnant or breastfeeding or are thinking of becoming pregnant, while taking liothyronine sodium.

Important Information

• Inform patients that the liothyronine in liothyronine sodium tablets is intended to replace a hormone that is normally produced by the thyroid gland. Generally replacement therapy is to be taken for life.
• Inform patients that liothyronine sodium should not be used as a primary or adjunctive therapy in a weight control program.
• Instruct patients to notify their healthcare provider if they are taking any other medications, including prescription and over-the-counter preparations.
• Instruct patients to notify their healthcare provider of any other medical conditions, particularly heart disease, diabetes, clotting disorders, and adrenal or pituitary gland problems, as the dose of medications used to control these other conditions may need to be adjusted while taking liothyronine sodium. If patents are taking anticoagulants (blood thinners), their clotting status should be checked frequently.
• Instruct patients to notify their physician or dentist if they are taking liothyronine sodium prior to any surgery.

Adverse Reactions

• Instruct patients to notify their healthcare provider if they experience any of the following symptoms: rapid or irregular heartbeat, chest pain, shortness of breath, leg cramps, headache, nervousness, irritability, sleeplessness, tremors, change in appetite, weight gain or loss, vomiting, diarrhea, excessive sweating, heat intolerance, fever, changes in menstrual periods, hives or skin rash, or any other unusual medical event[seeAdverse Reactions (6)].
• Inform patients that partial hair loss may occur rarely during the first few months of liothyronine sodium therapy; this is usually temporary[seeAdverse Reactions (6)].

This product's label may have been updated. For current full prescribing information, please visit www.greenstonellc.com

LAB-0960-4.0

1. No Title 1572549712
2. No Title 1572551629
3. No Title 1572551679
4. No Title 1572551814
5. No Title 1572552260
6. No Title 1572554005
7. No Title 1572554583
8. Liothyronine Sodium Tablets, Usp
9. No Title 1572449417
10. Liothyronine Sodium 25 Mcg
11. See Full Prescribing Information For Complete Boxed Warning.
12. 2 Dosage And Administration
13. Principal Display Panel - 5 Mcg Tablet Bottle Label
14. Principal Display Panel - 25 Mcg Tablet Bottle Label
15. Principal Display Panel - 50 Mcg Tablet Bottle Label
16. No Title 1572453160
17. Liothyronine Sodium 5 Mcg
18. Boxed Warning
19. Indications & Usage
20. Dosage & Administration
21. Principal Display Panel
22. No Title 1572454129
23. Liothyronine Sodium 50mcg Tablet
24. Highlights Of Prescribing Information
25. Warning: Not For Treatment Of Obesity Or For Weight Losssee Full Prescribing Information For Complete Boxed Warning.
26. Recent Major Changes
27. Indications And Usage
28. Dosage And Administration
29. Dosage Forms And Strengths
30. Contraindications
31. Warnings And Precautions
32. Adverse Reactions
33. Drug Interactions
34. Use In Specific Populations
35. Warning: Not For Treatment Of Obesity Or For Weight Loss
36. 1 Indications And Usage
37. 2 Dosage And Administration
38. 3 Dosage Forms And Strengths
39. 4 Contraindications
40. 5 Warnings And Precautions
41. 6 Adverse Reactions
42. 7 Drug Interactions
43. 8 Use In Specific Populations
44. 10 Overdosage
45. 11 Description
46. 12 Clinical Pharmacology
47. 13 Nonclinical Toxicology
48. 16 How Supplied/storage And Handling
49. Liothyronine Sodium Tablets, Usp 50 Mcg- 90 Tablets Container Label
50. No Title 1572455335
51. Liothyronine Sodium Tablets, Usp 5 Mcg
52. No Title 1572456733
53. Liothyronine Sodium 5mcg
54. Package Label.principal Display Panel
55. No Title 1572457763
56. No Title 1572448756
57. Description
58. Clinical Pharmacology
59. Warnings
60. Precautions
61. Overdosage
62. How Supplied
63. Storage
64. Liothyronine Sodium

No Title 1572549712 ⮝

Distributed by:
Paddock Laboratories, Inc.
Minneapolis, MN 55427

Repackaged By :
Aidarex Pharmaceuticals LLC,
Corona, CA 92880

Rev 11/2008

No Title 1572551629 ⮝

Distributed By Perrigo Minneapolis, MN 55427

60509 1R900 RC J2 Rev 05-14 B

No Title 1572551679 ⮝

Drugs with thyroid hormone activity, alone or together with other therapeutic agents, have been used for the treatment of obesity. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.

No Title 1572551814 ⮝

Drugs with thyroid hormone activity, alone or together with other therapeutic agents, have been used for the treatment of obesity. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.

No Title 1572552260 ⮝

Distributed By Perrigo Minneapolis, MN 55427

60509 1R900 RC J2 Rev 05-14 B

No Title 1572554005 ⮝

Drugs with thyroid hormone activity, alone or together with other therapeutic agents, have been used for the treatment of obesity. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.

No Title 1572554583 ⮝

Drugs with thyroid hormone activity, alone or together with other therapeutic agents, have been used for the treatment of obesity. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.

Liothyronine Sodium Tablets, Usp ⮝

Drugs with thyroid hormone activity, alone or together with other therapeutic agents, have been used for the treatment of obesity. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.

No Title 1572449417 ⮝

The use of thyroid hormones in the therapy of obesity, alone or combined with other drugs, is unjustified and has been shown to be ineffective. Neither is their use justified for the treatment of male or female infertility unless this condition is accompanied by hypothyroidism.

Thyroid hormones should be used with great caution in a number of circumstances where the integrity of the cardiovascular system, particularly the coronary arteries, is suspected. These include patients with angina pectoris or the elderly, in whom there is a greater likelihood of occult cardiac disease. In these patients, liothyronine sodium therapy should be initiated with low doses, with due consideration for its relatively rapid onset of action. Starting dosage of Liothyronine Sodium Tablets, USP is 5 mcg daily, and should be increased by no more than 5 mcg increments at 2-week intervals. When, in such patients, a euthyroid state can only be reached at the expense of an aggravation of the cardiovascular disease, thyroid hormone dosage should be reduced.

Morphologic hypogonadism and nephrosis should be ruled out before the drug is administered. If hypopituitarism is present, the adrenal deficiency must be corrected prior to starting the drug.

Myxedematous patients are very sensitive to thyroid; dosage should be started at a very low level and increased gradually.

Severe and prolonged hypothyroidism can lead to a decreased level of adrenocortical activity commensurate with the lowered metabolic state. When thyroid-replacement therapy is administered, the metabolism increases at a greater rate than adrenocortical activity. This can precipitate adrenocortical insufficiency. Therefore, in severe and prolonged hypothyroidism, supplemental adrenocortical steroids may be necessary. In rare instances the administration of thyroid hormone may precipitate a hyperthyroid state or may aggravate existing hyperthyroidism.

Liothyronine Sodium 25 Mcg ⮝

LIOTHYRONINE SODIUM liothyronine sodium tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:68151-0238(NDC:0574-0222) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Liothyronine Sodium (UNII: GCA9VV7D2N) (liothyronine - UNII:06LU7C9H1V) liothyronine 25 ug

Inactive Ingredients Ingredient Name Strength CALCIUM SULFATE (UNII: WAT0DDB505) CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U) HYPROMELLOSES (UNII: 3NXW29V3WO) TALC (UNII: 7SEV7J4R1U) SILICON DIOXIDE (UNII: ETJ7Z6XBU4)

Product Characteristics Color WHITE Score 2 pieces Shape ROUND Size 7mm Flavor Imprint Code 25;222 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:68151-0238-0 1 in 1 PACKAGE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090097 03/23/2009

Labeler - Carilion Materials Management (079239644)

Registrant - Carilion Materials Management (079239644)

Establishment
Name	Address	ID/FEI	Business Operations
Carilion Materials Management		079239644	REPACK(68151-0238)

Revised: 5/2014 Document Id: 16085835-5a05-4514-8b4d-ee1ec49833a0 34391-3 Set id: fecd164d-1344-4d2f-97a7-ebe972470d2b Version: 2 Effective Time: 20140520 Carilion Materials Management

See Full Prescribing Information For Complete Boxed Warning. ⮝

• Thyroid hormones, including liothyronine sodium, should not be used for the treatment of obesity or for weight loss.
• Doses beyond the range of daily hormonal requirements may produce serious or even life-threatening manifestations of toxicity (6, 7.7, 10).

2 Dosage And Administration ⮝

2.1 General Principles of Dosing

The dose of liothyronine sodium for hypothyroidism or pituitary TSH suppression depends on a variety of factors including: the patient's age, body weight, cardiovascular status, concomitant medical conditions (including pregnancy), concomitant medications, co-administered food and the specific nature of the condition being treated [see Dosage and Administration (2.2, 2.3, 2.4), Warnings and Precautions (5), and Drug Interactions (7)]. Dosing must be individualized to account for these factors and dose adjustments made based on periodic assessment of the patient's clinical response and laboratory parameters [see Dosage and Administration (2.4)].

Administer liothyronine sodium tablets orally once daily.

2.2 Recommended Dosage for Hypothyroidism

Adults

The recommended starting dosage is 25 mcg orally once daily. Increase the dose by 25 mcg daily every 1 or 2 weeks, if needed. The usual maintenance dose is 25 mcg to 75 mcg once daily.

For elderly patients or patients with underlying cardiac disease, start with liothyronine sodium 5 mcg once daily and increase by 5 mcg increments at the recommended intervals.

Serum TSH is not a reliable measure of liothyronine sodium dose adequacy in patients with secondary or tertiary hypothyroidism and should not be used to monitor therapy. Use the serum T3 level to monitor adequacy of therapy in this patient population.

Pediatric Patients

The recommended starting dosage is 5 mcg once daily, with a 5 mcg increase every 3 to 4 days until the desired response is achieved. Infants a few months old may require 20 mcg once daily for maintenance. At 1 year of age, 50 mcg once daily may be required. Above 3 years of age, the full adult dosage may be necessary [see Use in Specific Populations (8.4)].

Newborns (0 to 3 months) at Risk for Cardiac Failure:

Consider a lower starting dose in infants at risk for cardiac failure. Increase the dose as needed based on clinical and laboratory response.

Pediatric Patients at Risk for Hyperactivity:

To minimize the risk of hyperactivity in pediatric patients, start at one-fourth the recommended full replacement dose, and increase on a weekly basis by one-fourth the full recommended replacement dose until the full recommended replacement dose is reached.

Pregnancy

Pre-existing Hypothyroidism:

Thyroid hormone dose requirements may increase during pregnancy. Measure serum TSH and free-T4 as soon as pregnancy is confirmed and, at minimum, during each trimester of pregnancy. In patients with primary hypothyroidism, maintain serum TSH in the trimester-specific reference range. For patients with serum TSH above the normal trimester-specific range, increase the dose of thyroid hormone and measure TSH every 4 weeks until a stable dose is reached and serum TSH is within the normal trimester-specific range. Reduce thyroid hormone dosage to pre-pregnancy levels immediately after delivery and measure serum TSH levels 4 to 8 weeks postpartum to ensure thyroid hormone dose is appropriate.

2.3 Recommended Dosage for TSH Suppression in Well-Differentiated Thyroid Cancer

The dose of liothyronine sodium should target TSH levels within the desired therapeutic range. This may require higher doses, depending on the target level for TSH suppression.

2.4 Recommended Dosage for Thyroid Suppression Test

The recommended dose is 75 mcg to 100 mcg daily for 7 days, with radioactive iodine uptake being determined before and after the 7 day administration of liothyronine sodium. If thyroid function is normal, the radioiodine uptake will drop significantly after treatment. A 50% or greater suppression of uptake indicates a normal thyroid-pituitary axis.

2.5 Switching from Levothyroxine to Liothyronine Sodium

Liothyronine sodium has a rapid onset of action and residual effects of the other thyroid preparation may persist for the first several weeks after initiating liothyronine sodium therapy. When switching a patient to liothyronine sodium, discontinue levothyroxine therapy and initiate liothyronine sodium at a low dosage. Gradually increase the liothyronine sodium dose according to the patient's response.

2.6 Monitoring TSH and Triiodothyronine (T3) Levels

Assess the adequacy of therapy by periodic assessment of laboratory tests and clinical evaluation. Persistent clinical and laboratory evidence of hypothyroidism despite an apparent adequate replacement dose of liothyronine sodium may be evidence of inadequate absorption, poor compliance, drug interactions, or a combination of these factors.

Adults

In adult patients with primary hypothyroidism, monitor serum TSH periodically after initiation of the therapy or any change in dose. To check the immediate response to therapy before the TSH has had a chance to respond or if your patient's status needs to be assessed prior to that point, measurement of total T3 would be most appropriate. In patients on a stable and appropriate replacement dose, evaluate clinical and biochemical response every 6 to 12 months and whenever there is a change in the patient's clinical status.

Pediatrics

In pediatric patients with hypothyroidism, assess the adequacy of replacement therapy by measuring serum TSH and T3 levels. For pediatric patients three years of age and older, the recommended monitoring is every 3 to 12 months thereafter, following dose stabilization until growth and puberty are completed. Poor compliance or abnormal values may necessitate more frequent monitoring. Perform routine clinical examination, including assessment of development, mental and physical growth, and bone maturation, at regular intervals.

While the general aim of therapy is to normalize the serum TSH level, TSH may not normalize in some patients due to in utero hypothyroidism causing a resetting of pituitary-thyroid feedback. Failure of the serum TSH to decrease below 20 IU per liter after initiation of liothyronine sodium therapy may indicate the child is not receiving adequate therapy. Assess compliance, dose of medication administered, and method of administration prior to increasing the dose of liothyronine sodium [see Warnings and Precautions (5.1) and Use in Specific Populations (8.4)].

Secondary and Tertiary Hypothyroidism

Monitor serum T3 levels and maintain in the normal range.

Principal Display Panel - 5 Mcg Tablet Bottle Label ⮝

NDC 59762-1206-1
100 Tablets

GREENSTONE BRAND

liothyronine
sodium tablets

5 mcg

Rx only

Principal Display Panel - 25 Mcg Tablet Bottle Label ⮝

NDC 59762-1207-1
100 Tablets

GREENSTONE BRAND

liothyronine
sodium tablets

25 mcg

Rx only

Principal Display Panel - 50 Mcg Tablet Bottle Label ⮝

NDC 59762-1208-1
100 Tablets

GREENSTONE BRAND

liothyronine
sodium tablets

50 mcg

Rx only

LIOTHYRONINE SODIUM liothyronine sodium tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:59762-1206 Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LIOTHYRONINE SODIUM (UNII: GCA9VV7D2N) (LIOTHYRONINE - UNII:06LU7C9H1V) LIOTHYRONINE 5 ug

Product Characteristics Color WHITE (white to off-white) Score no score Shape ROUND Size 6mm Flavor Imprint Code KPI;115 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:59762-1206-1 100 in 1 BOTTLE; Type 0: Not a Combination Product 02/06/2019

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA AUTHORIZED GENERIC NDA010379 02/06/2019

LIOTHYRONINE SODIUM liothyronine sodium tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:59762-1207 Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LIOTHYRONINE SODIUM (UNII: GCA9VV7D2N) (LIOTHYRONINE - UNII:06LU7C9H1V) LIOTHYRONINE 25 ug

Product Characteristics Color WHITE (white to off-white) Score 2 pieces Shape ROUND Size 7mm Flavor Imprint Code KPI;116 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:59762-1207-1 100 in 1 BOTTLE; Type 0: Not a Combination Product 06/24/2019

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA AUTHORIZED GENERIC NDA010379 06/24/2019

LIOTHYRONINE SODIUM liothyronine sodium tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:59762-1208 Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LIOTHYRONINE SODIUM (UNII: GCA9VV7D2N) (LIOTHYRONINE - UNII:06LU7C9H1V) LIOTHYRONINE 50 ug

Product Characteristics Color WHITE (white to off-white) Score 2 pieces Shape ROUND Size 8mm Flavor Imprint Code KPI;117 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:59762-1208-1 100 in 1 BOTTLE; Type 0: Not a Combination Product 06/24/2019

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA AUTHORIZED GENERIC NDA010379 06/24/2019

Labeler - Greenstone LLC (825560733)

Registrant - Pfizer Inc (113480771)

Establishment
Name	Address	ID/FEI	Business Operations
Peptido GmbH		327335410	API MANUFACTURE(59762-1206, 59762-1207, 59762-1208)

Revised: 10/2019 Document Id: 8d7243a3-9b15-4c20-add5-b0e9a63b43e1 34391-3 Set id: 115a84c2-0126-4dd7-816e-1873875f1e49 Version: 4 Effective Time: 20191007 Greenstone LLC

No Title 1572453160 ⮝

The use of thyroid hormones in the therapy of obesity, alone or combined with other drugs, is unjustified and has been shown to be ineffective. Neither is their use justified for the treatment of male or female infertility unless this condition is accompanied by hypothyroidism.

Thyroid hormones should be used with great caution in a number of circumstances where the integrity of the cardiovascular system, particularly the coronary arteries, is suspected. These include patients with angina pectoris or the elderly, in whom there is a greater likelihood of occult cardiac disease. In these patients, liothyronine sodium therapy should be initiated with low doses, with due consideration for its relatively rapid onset of action. Starting dosage of Liothyronine Sodium Tablets, USP is 5 mcg daily, and should be increased by no more than 5 mcg increments at 2-week intervals. When, in such patients, a euthyroid state can only be reached at the expense of an aggravation of the cardiovascular disease, thyroid hormone dosage should be reduced.

Morphologic hypogonadism and nephrosis should be ruled out before the drug is administered. If hypopituitarism is present, the adrenal deficiency must be corrected prior to starting the drug.

Myxedematous patients are very sensitive to thyroid; dosage should be started at a very low level and increased gradually.

Severe and prolonged hypothyroidism can lead to a decreased level of adrenocortical activity commensurate with the lowered metabolic state. When thyroid-replacement therapy is administered, the metabolism increases at a greater rate than adrenocortical activity. This can precipitate adrenocortical insufficiency. Therefore, in severe and prolonged hypothyroidism, supplemental adrenocortical steroids may be necessary. In rare instances the administration of thyroid hormone may precipitate a hyperthyroid state or may aggravate existing hyperthyroidism.

Liothyronine Sodium 5 Mcg ⮝

LIOTHYRONINE SODIUM liothyronine sodium tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:68151-0237(NDC:0574-0220) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength Liothyronine Sodium (UNII: GCA9VV7D2N) (liothyronine - UNII:06LU7C9H1V) liothyronine 5 ug

Inactive Ingredients Ingredient Name Strength CALCIUM SULFATE (UNII: WAT0DDB505) CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U) HYPROMELLOSES (UNII: 3NXW29V3WO) TALC (UNII: 7SEV7J4R1U) SILICON DIOXIDE (UNII: ETJ7Z6XBU4)

Product Characteristics Color WHITE Score no score Shape ROUND Size 7mm Flavor Imprint Code 5;220 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:68151-0237-0 1 in 1 PACKAGE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090097 03/23/2009

Labeler - Carilion Materials Management (079239644)

Registrant - Carilion Materials Management (079239644)

Establishment
Name	Address	ID/FEI	Business Operations
Carilion Materials Management		079239644	REPACK(68151-0237)

Revised: 5/2014 Document Id: efcddc0e-454b-45e3-b78c-1e9f5a2cdb8a 34391-3 Set id: bc225ead-22b5-444e-9254-01c6250a1175 Version: 2 Effective Time: 20140520 Carilion Materials Management

Boxed Warning ⮝

Drugs with thyroid hormone activity, alone or together with other therapeutic agents, have been used for the treatment of obesity. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.

Indications & Usage ⮝

Thyroid hormone drugs are indicated:
As replacement or supplemental therapy in patients with hypothyroidism of any etiology, except transient hypothyroidism during the recovery phase of subacute thyroiditis. This category includes cretinism, myxedema and ordinary hypothyroidism in patients of any age (pediatric patients, adults, the elderly), or state (including pregnancy); primary hypothyroidism resulting from functional deficiency, primary atrophy, partial or total absence of thyroid gland, or the effects of surgery, radiation, or drugs, with or without the presence of goiter; and secondary (pituitary) or tertiary (hypothalamic) hypothyroidism (see WARNINGS).
As pituitary thyroid-stimulating hormone (TSH) suppressants, in the treatment or prevention of various types of euthyroid goiters, including thyroid nodules, subacute or chronic lymphocytic thyroiditis (Hashimoto s) and multinodular goiter.
As diagnostic agents in suppression tests to differentiate suspected mild hyperthyroidism or thyroid gland autonomy.

Liothyronine sodium tablets can be used in patients allergic to desiccated thyroid or thyroid extract derived from pork or beef.

Dosage & Administration ⮝

The dosage of thyroid hormones is determined by the indication and must in every case be individualized according to patient response and laboratory findings.

Liothyronine sodium tablets are intended for oral administration; once-a-day dosage is recommended. Although liothyronine sodium has a rapid cutoff, its metabolic effects persist for a few days following discontinuance.

Mild Hypothyroidism: Recommended starting dosage is 25 mcg daily. Daily dosage then may be increased by up to 25 mcg every 1 or 2 weeks. Usual maintenance dose is 25 to 75 mcg daily.

The rapid onset and dissipation of action of liothyronine sodium (T3), as compared with levothyroxine sodium (T4), has led some clinicians to prefer its use in patients who might be more susceptible to the untoward effects of thyroid medication. However, the wide swings in serum T3 levels that follow its administration and the possibility of more pronounced cardiovascular side effects tend to counterbalance the stated advantages.

Liothyronine sodium tablets may be used in preference to levothyroxine (T4) during radioisotope scanning procedures, since induction of hypothyroidism in those cases is more abrupt and can be of shorter duration. It may also be preferred when impairment of peripheral conversion of T4 to T3 is suspected.

Myxedema: Recommended starting dosage is 5 mcg daily. This may be increased by 5 to 10 mcg daily every 1 or 2 weeks. When 25 mcg daily is reached, dosage may be increased by 5 to 25 mcg every 1 or 2 weeks until a satisfactory therapeutic response is attained. Usual maintenance dose is 50 to 100 mcg daily.

Myxedema Coma: Myxedema coma is usually precipitated in the hypothyroid patient of long standing by intercurrent illness or drugs such as sedatives and anesthetics and should be considered a medical emergency.

An intravenous preparation of liothyronine sodium is marketed by JONES PHARMA INCORPORATED, under the trade name Triostat for use in myxedema coma/precoma.

Congenital Hypothyroidism: Recommended starting dosage is 5 mcg daily, with a 5 mcg increment every 3 to 4 days until the desired response is achieved. Infants a few months old may require only 20 mcg daily for maintenance. At 1 year, 50 mcg daily may be required. Above 3 years, full adult dosage may be necessary (see PRECAUTIONS, Pediatric Use).

Simple (non-toxic) Goiter: Recommended starting dosage is 5 mcg daily. This dosage may be increased by 5 to 10 mcg daily every 1 or 2 weeks. When 25 mcg daily is reached, dosage may be increased every week or two by 12.5 or 25 mcg. Usual maintenance dosage is 75 mcg daily.

In the elderly or in pediatric patients, therapy should be started with 5 mcg daily and increased only by 5 mcg increments at the recommended intervals.

When switching a patient to Liothyronine Sodium tablets from thyroid, L-thyroxine or thyroglobulin, discontinue the other medication, initiate liothyronine sodium at a low dosage, and increase gradually according to the patient's response. When selecting a starting dosage, bear in mind that this drug has a rapid onset of action, and that residual effects of the other thyroid preparation may persist for the first several weeks of therapy.

Thyroid Suppression Therapy: Administration of thyroid hormone in doses higher than those produced physiologically by the gland results in suppression of the production of endogenous hormone. This is the basis for the thyroid suppression test and is used as an aid in the diagnosis of patients with signs of mild hyperthyroidism in whom baseline laboratory tests appear normal or to demonstrate thyroid gland autonomy in patients with Graves ophthalmopathy. 131I uptake is determined before and after the administration of the exogenous hormone. A 50% or greater suppression of uptake indicates a normal thyroid-pituitary axis and thus rules out thyroid gland autonomy.

Each 5 mcg tablet contains liothyronine sodium equivalent to 5 mcg of liothyronine. Each 25 mcg tablet contains liothyronine sodium equivalent to 25 mcg of liothyronine. Each 50 mcg tablet contains liothyronine sodium equivalent to 50 mcg of liothyronine.

Liothyronine sodium tablets are given in doses of 75 to 100 mcg/day for 7 days, and radioactive iodine uptake is determined before and after administration of the hormone. If thyroid function is under normal control, the radioiodine uptake will drop significantly after treatment. Liothyronine sodium tablets should be administered cautiously to patients in whom there is a strong suspicion of thyroid gland autonomy, in view of the fact that the exogenous hormone effects will be additive to the endogenous source.

Principal Display Panel ⮝

NDC: 51655-122-52

MFG: 42794-020-02

Liothyronine Sodium 50 mcg

30 Tablets

Rx Only

Lot#

Exp. Date:

Each tablet contains liothyroninesodium equivalent to 50 mcg of liothyronine.

Dosage: See prescriber's instructions.

Store between 59-86 degrees F.

Keep out of reach of children.

Medication guide is found at www.fda.gov/drugs/drugsafety/ucm085729

Mfg by Sigmapharm laboratories, LLC Bensalem, PA 19020 Lot#

Repackaged by Northwind Pharmaceuticals, Indianapolis, IN 46256

LIOTHYRONINE SODIUM liothyronine sodium tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:51655-122(NDC:42794-020) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LIOTHYRONINE SODIUM (UNII: GCA9VV7D2N) (LIOTHYRONINE - UNII:06LU7C9H1V) LIOTHYRONINE 50 ug

Product Characteristics Color white Score 2 pieces Shape ROUND Size 8mm Flavor Imprint Code 20 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:51655-122-52 30 in 1 BOTTLE, DISPENSING

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA200295 12/29/2014

Labeler - Northwind Pharmaceuticals (036986393)

Registrant - Northwind Pharmaceuticals (036986393)

Establishment
Name	Address	ID/FEI	Business Operations
Northwind Pharmaceuticals		036986393	repack(51655-122)

Revised: 1/2015 Document Id: 05548cb8-6ee3-47a4-960e-6b2d576240aa 34391-3 Set id: e6c9e50b-d5e6-44b8-a601-82f7baf9b28e Version: 1 Effective Time: 20150122 Northwind Pharmaceuticals

No Title 1572454129 ⮝

Drugs with thyroid hormone activity, alone or together with other therapeutic agents, have been used for the treatment of obesity. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.

Liothyronine Sodium 50mcg Tablet ⮝

LIOTHYRONINE SODIUM liothyronine sodium tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:63629-6391(NDC:42794-019) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LIOTHYRONINE SODIUM (UNII: GCA9VV7D2N) (LIOTHYRONINE - UNII:06LU7C9H1V) LIOTHYRONINE 25 ug

Inactive Ingredients Ingredient Name Strength CALCIUM SULFATE DIHYDRATE (UNII: 4846Q921YM) STARCH, CORN (UNII: O8232NY3SJ) GELATIN, UNSPECIFIED (UNII: 2G86QN327L) MAGNESIUM STEARATE (UNII: 70097M6I30) MANNITOL (UNII: 3OWL53L36A)

Product Characteristics Color white (white to off-white) Score 2 pieces Shape ROUND Size 7mm Flavor Imprint Code 19 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:63629-6391-1 30 in 1 BOTTLE; Type 0: Not a Combination Product 09/17/2015

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA200295 11/30/2012

LIOTHYRONINE SODIUM liothyronine sodium tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:63629-6540(NDC:42794-018) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LIOTHYRONINE SODIUM (UNII: GCA9VV7D2N) (LIOTHYRONINE - UNII:06LU7C9H1V) LIOTHYRONINE 5 ug

Inactive Ingredients Ingredient Name Strength CALCIUM SULFATE DIHYDRATE (UNII: 4846Q921YM) STARCH, CORN (UNII: O8232NY3SJ) GELATIN, UNSPECIFIED (UNII: 2G86QN327L) MAGNESIUM STEARATE (UNII: 70097M6I30) MANNITOL (UNII: 3OWL53L36A)

Product Characteristics Color white (white to off-white) Score no score Shape ROUND Size 6mm Flavor Imprint Code 18 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:63629-6540-1 30 in 1 BOTTLE; Type 0: Not a Combination Product 07/23/2015 01/30/2019 2 NDC:63629-6540-2 90 in 1 BOTTLE; Type 0: Not a Combination Product 07/23/2015 01/30/2019 3 NDC:63629-6540-3 60 in 1 BOTTLE; Type 0: Not a Combination Product 07/23/2015 01/30/2019 4 NDC:63629-6540-4 18 in 1 BOTTLE; Type 0: Not a Combination Product 07/23/2015 01/30/2019 5 NDC:63629-6540-5 28 in 1 BOTTLE; Type 0: Not a Combination Product 07/23/2015 01/30/2019 6 NDC:63629-6540-6 100 in 1 BOTTLE; Type 0: Not a Combination Product 07/23/2015 01/30/2019

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA200295 12/03/2012 01/30/2019

LIOTHYRONINE SODIUM liothyronine sodium tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:63629-8154(NDC:42794-020) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LIOTHYRONINE SODIUM (UNII: GCA9VV7D2N) (LIOTHYRONINE - UNII:06LU7C9H1V) LIOTHYRONINE 50 ug

Product Characteristics Color white (white to off-white) Score 2 pieces Shape ROUND Size 8mm Flavor Imprint Code 20 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:63629-8154-1 30 in 1 BOTTLE; Type 0: Not a Combination Product 12/03/2012 2 NDC:63629-8154-2 60 in 1 BOTTLE; Type 0: Not a Combination Product 06/25/2019

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA200295 12/03/2012

Labeler - Bryant Ranch Prepack (171714327)

Establishment
Name	Address	ID/FEI	Business Operations
Bryant Ranch Prepack		171714327	REPACK(63629-8154, 63629-6391, 63629-6540) , RELABEL(63629-6391, 63629-6540, 63629-8154)

Revised: 8/2019 Document Id: b6d164bc-633a-4e49-a165-0faeb9a5ae7b 34391-3 Set id: 4cb7bf1c-49bd-4ecd-9419-2d035d7488ea Version: 11 Effective Time: 20190807 Bryant Ranch Prepack

Highlights Of Prescribing Information ⮝

These highlights do not include all the information needed to use LIOTHYRONINE SODIUM safely and effectively. See full prescribing information for LIOTHYRONINE SODIUM.

LIOTHYRONINE SODIUM tablets, for oral use
Initial U.S. Approval: 1956

Warning: Not For Treatment Of Obesity Or For Weight Losssee Full Prescribing Information For Complete Boxed Warning.  ⮝

• Thyroid hormones, including liothyronine sodium should not be used for the treatment of obesity or for weight loss.
• Doses beyond the range of daily hormonal requirements may produce serious or even life-threatening manifestations of toxicity ( 6, 7.7, 10)

Recent Major Changes ⮝

Indications and Usage (1.1, 1.2, 1.3)	12/2018
Dosage and Administration (2.1, 2.2, 2.3, 2.4, 2.5, 2.6)	12/2018
Contraindications (4)	12/2018
Warnings and Precautions (5.1, 5.2, 5.3, 5.4, 5.5, 5.6)	12/2018

Indications And Usage ⮝

Liothyronine sodium is an L-triiodothyronine (T3) indicated for:

• Hypothyroidism: As replacement in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism (1.1)
• Pituitary Thyroid-Stimulating Hormone (TSH) Suppression: As an adjunct to surgery and radioiodine therapy in the management of well-differentiated thyroid cancer (1.2)
• Thyroid Suppression Test: As a diagnostic agent in suppression tests to differentiate suspected mild hyperthyroidism or thyroid gland autonomy (1.3)

Limitations of Use:

- Not indicated for suppression of benign thyroid nodules and nontoxic diffuse goiter in iodine-sufficient patients. (1)

- Not indicated for treatment of hypothyroidism during the recovery phase of subacute thyroiditis. (1)

Dosage And Administration ⮝

• Administer liothyronine sodium orally once daily and individual dosage according to patient response and laboratory findings (2.1)
• See full prescribing information for recommended dosage for hypothyroidism (2.2) TSH suppression in well-differentiated thyroid cancer (2.3) and for thyroid suppression test (2.4)
• When switching a patient to liothyronine sodium, discontinue levothyroxine therapy and initiate liothyronine sodium at a low dosage. Gradually increase the dose according to the patient's response (2.5)
• Adequacy of therapy determined with periodic monitoring of TSH and T3 levels as well as clinical status (2.6)

Dosage Forms And Strengths ⮝

Tablets: 5 mcg, 25 mcg, 50 mcg (3)

Contraindications ⮝

Uncorrected adrenal cortical insufficiency (4)

Warnings And Precautions ⮝

• Cardiac adverse reactions in the elderly and in patients with underlying cardiovascular disease: Initiate liothyronine sodium 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 liothyronine sodium 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)

Adverse Reactions ⮝

Most common adverse reactions for liothyronine sodium are primarily those of hyperthyroidism due to therapeutic overdosage: arrhythmias, myocardial infarction, dyspnea, headache, nervousness, irritability, insomnia, tremors, muscle weakness, increased appetite, weight loss, diarrhea, heat intolerance, menstrual irregularities, and skin rash (6)

To report SUSPECTED ADVERSE REACTIONS, contact Greenstone LLC at 1-800-438-1985 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drug Interactions ⮝

See full prescribing information for drugs that affect thyroid hormone pharmacokinetics and metabolism (e.g., absorption, synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to liothyronine sodium (7)

Use In Specific Populations ⮝

Pregnancy may require the use of higher doses of thyroid hormone (2.2, 8.1)

See 17 for PATIENT COUNSELING INFORMATION.

Revised: 10/2019

Warning: Not For Treatment Of Obesity Or For Weight Loss ⮝

• Thyroid hormones, including LIOTHYRONINE SODIUM, either alone or with other therapeutic agents, should not be used for the treatment of obesity or for weight loss.
• In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction.
• Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects [see Adverse Reactions (6), Drug Interactions (7.7), and Overdosage (10)].

1 Indications And Usage ⮝

1.1 Hypothyroidism

Liothyronine sodium is indicated as a replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism.

1.2 Pituitary Thyroid-Stimulating Hormone (TSH) Suppression

Liothyronine sodium is indicated as an adjunct to surgery and radioiodine therapy in the management of well-differentiated thyroid cancer.

1.3 Thyroid Suppression Test

Liothyronine sodium is indicated as a diagnostic agent in suppression tests to differentiate suspected mild hyperthyroidism or thyroid gland autonomy.

Limitations of Use

• Liothyronine sodium is not indicated for suppression of benign thyroid nodules and nontoxic diffuse goiter in iodine-sufficient patients as there are no clinical benefits and overtreatment with liothyronine sodium may induce hyperthyroidism [see Warnings and Precautions (5.4)].
• Liothyronine sodium is not indicated for treatment of hypothyroidism during the recovery phase of subacute thyroiditis.

2 Dosage And Administration ⮝

2.1 General Principles of Dosing

The dose of Liothyronine Sodium Tablets, USP for hypothyroidism or pituitary Thyroid-Stimulating Hormone (TSH) suppression depends on a variety of factors including: the patient's age, body weight, cardiovascular status, concomitant medical conditions (including pregnancy), concomitant medications, co-administered food and the specific nature of the condition being treated [see Dosage and Administration (2.2, 2.3, 2.4), Warnings and Precautions (5), and Drug Interactions (7)] . Dosing must be individualized to account for these factors and dose adjustments made based on periodic assessment of the patient's clinical response and laboratory parameters [see Dosage and Administration (2.4)].

Administer Liothyronine Sodium Tablets, USP orally once daily.

2.2 Recommended Dosage for Hypothyroidism

Adults
The recommended starting dosage is 25 mcg orally once daily. Increase the dose by 25 mcg daily every 1 or 2 weeks, if needed. The usual maintenance dose is 25 mcg to 75 mcg once daily.

For elderly patients or patients with underlying cardiac disease, start with Liothyronine Sodium Tablets, USP 5 mcg once daily and increase by 5 mcg increments at the recommended intervals.

Serum TSH is not a reliable measure of liothyronine sodium dose adequacy in patients with secondary or tertiary hypothyroidism and should not be used to monitor therapy. Use the serum T3 level to monitor adequacy of therapy in this patient population.

Pediatric Patients
The recommended starting dosage is 5 mcg once daily, with a 5 mcg increase every 3 to 4 days until the desired response is achieved. Infants a few months old may require 20 mcg once daily for maintenance. At 1 year of age, 50 mcg once daily may be required. Above 3 years of age, the full adult dosage may be necessary [see Use in Specific Populations (8.4)].

Newborns (0 to 3 months) at Risk for Cardiac Failure:
Consider a lower starting dose in infants at risk for cardiac failure. Increase the dose as needed based on clinical and laboratory response.

Pediatric Patients at Risk for Hyperactivity:
To minimize the risk of hyperactivity in pediatric patients, start at one-fourth the recommended full replacement dose, and increase on a weekly basis by one-fourth the full recommended replacement dose until the full recommended replacement dose is reached.

Pregnancy
Pre-existing Hypothyroidism: Thyroid hormone dose requirements may increase during pregnancy. Measure serum TSH and free-T4 as soon as pregnancy is confirmed and, at minimum, during each trimester of pregnancy. In patients with primary hypothyroidism, maintain serum TSH in the trimester-specific reference range. For patients with serum TSH above the normal trimester-specific range, increase the dose of thyroid hormone and measure TSH every 4 weeks until a stable dose is reached and serum TSH is within the normal trimester-specific range. Reduce thyroid hormone dosage to pre-pregnancy levels immediately after delivery and measure serum TSH levels 4 to 8 weeks postpartum to ensure thyroid hormone dose is appropriate.

2.3 Recommended Dosage for TSH Suppression in Well-Differentiated Thyroid Cancer

The dose of Liothyronine Sodium Tablets, USP should target TSH levels within the desired therapeutic range. This may require higher doses, depending on the target level for TSH suppression.

2.4 Recommended Dosage for Thyroid Suppression Test

The recommended dose is 75 mcg to 100 mcg daily for 7 days, with radioactive iodine uptake being determined before and after the 7 day administration of Liothyronine Sodium Tablets, USP. If thyroid function is normal, the radioiodine uptake will drop significantly after treatment. A 50% or greater suppression of uptake indicates a normal thyroid-pituitary axis.

2.5 Switching from Levothyroxine to Liothyronine Sodium Tablets, USP

Liothyronine sodium has a rapid onset of action and residual effects of the other thyroid preparation may persist for the first several weeks after initiating liothyronine sodium therapy. When switching a patient to Liothyronine Sodium Tablets, USP, discontinue levothyroxine therapy and initiate Liothyronine Sodium Tablets, USP at a low dosage. Gradually increase the liothyronine sodium dose according to the patient's response.

2.6 Monitoring TSH and Triiodothyronine (T3) Levels

Assess the adequacy of therapy by periodic assessment of laboratory tests and clinical evaluation. Persistent clinical and laboratory evidence of hypothyroidism despite an apparent adequate replacement dose of Liothyronine Sodium Tablets, USP may be evidence of inadequate absorption, poor compliance, drug interactions, or a combination of these factors.

Adults
In adult patients with primary hypothyroidism, monitor serum TSH periodically after initiation of the therapy or any change in dose. To check the immediate response to therapy before the TSH has had a chance to respond or if your patient's status needs to be assessed prior to that point, measurement of total T3 would be most appropriate. In patients on a stable and appropriate replacement dose, evaluate clinical and biochemical response every 6 to 12 months and whenever there is a change in the patient's clinical status.

Pediatrics
In pediatric patients with hypothyroidism, assess the adequacy of replacement therapy by measuring serum TSH and T3 levels. For pediatric patients three years of age and older, the recommended monitoring is every 3 to 12 months thereafter, following dose stabilization until growth and puberty are completed. Poor compliance or abnormal values may necessitate more frequent monitoring. Perform routine clinical examination, including assessment of development, mental and physical growth, and bone maturation, at regular intervals.

While the general aim of therapy is to normalize the serum TSH level, TSH may not normalize in some patients due to in utero hypothyroidism causing a resetting of pituitary-thyroid feedback. Failure of the serum TSH to decrease below 20 IU per liter after initiation of liothyronine sodium therapy may indicate the child is not receiving adequate therapy. Assess compliance, dose of medication administered, and method of administration prior to increasing the dose of Liothyronine Sodium Tablets, USP [see Warnings and Precautions (5.1) andUse in Specific Populations (8.4)].

Secondary and Tertiary Hypothyroidism
Monitor serum T3 levels and maintain in the normal range.

3 Dosage Forms And Strengths ⮝

Tablets (round, white to off-white) available as follows:

• 5 mcg: debossed with KPI on one side and 115 on the other side
• 25 mcg: scored on one side and debossed with KPI and 116 on the other side
• 50 mcg: scored on one side and debossed with KPI and 117 on the other side

4 Contraindications ⮝

Liothyronine sodium is contraindicated in patients with uncorrected adrenal insufficiency [see Warnings and Precautions (5.3)].

5 Warnings And Precautions ⮝

5.1 Cardiac Adverse Reactions in the Elderly and in Patients with Underlying Cardiovascular Disease

Overtreatment with thyroid hormone 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 liothyronine sodium 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) and Use in Specific Populations (8.5)].

Monitor for cardiac arrhythmias during surgical procedures in patients with coronary artery disease receiving suppressive liothyronine sodium therapy. Monitor patients receiving concomitant liothyronine sodium and sympathomimetic agents for signs and symptoms of coronary insufficiency. If cardiovascular symptoms develop or worsen, reduce or withhold the liothyronine sodium dose 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 thyroid hormone 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 liothyronine sodium [see Contraindications (4)].

5.4 Prevention of Hyperthyroidism or Incomplete Treatment of Hypothyroidism

Liothyronine sodium has a narrow therapeutic index. Over- or undertreatment with liothyronine sodium may have negative effects on growth and development, cardiovascular function, bone metabolism, reproductive function, cognitive function, emotional state, gastrointestinal function, and on glucose and lipid metabolism. Titrate the dose of liothyronine sodium 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 liothyronine sodium and adjust the dose as necessary [see Drug Interactions (7) and Clinical Pharmacology (12.3)].

5.5 Worsening of Diabetic Control

Addition of thyroid hormone 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 liothyronine sodium [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 thyroid hormone 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 liothyronine sodium that achieves the desired clinical and biochemical response to mitigate against this risk.

6 Adverse Reactions ⮝

Adverse reactions associated with liothyronine sodium therapy are primarily those of hyperthyroidism due to therapeutic overdosage [see Warnings and Precautions (5.4) and Overdosage (10)]. They include the following:

General: fatigue, increased appetite, weight loss, heat intolerance, fever, excessive sweating

Central nervous system: headache, hyperactivity, nervousness, anxiety, irritability, emotional lability, insomnia

Musculoskeletal: tremors, muscle weakness and cramps

Cardiovascular: palpitations, tachycardia, arrhythmias, increased pulse and blood pressure, heart failure, angina, myocardial infarction, cardiac arrest

Respiratory: dyspnea

Gastrointestinal: diarrhea, vomiting, abdominal cramps, elevations in liver function tests

Dermatologic: hair loss, flushing

Endocrine: decreased bone mineral density

Reproductive: menstrual irregularities, impaired fertility

Adverse Reactions in Pediatric Patients

Pseudotumor cerebri and slipped capital femoral epiphysis have been reported in pediatric patients receiving thyroid replacement therapy. Overtreatment may result in craniosynostosis in infants and premature closure of the epiphyses in pediatric patients with resultant compromised adult height.

Hypersensitivity Reactions

Hypersensitivity reactions to inactive ingredients have occurred in patients treated with thyroid hormone products. These include urticaria, pruritus, skin rash, flushing, angioedema, various gastrointestinal symptoms (abdominal pain, nausea, vomiting and diarrhea), fever, arthralgia, serum sickness and wheezing.

7 Drug Interactions ⮝

7.1 Drugs Known to Affect Thyroid Hormone Pharmacokinetics

Many drugs can exert effects on thyroid hormone pharmacokinetics (e.g. absorption, synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to liothyronine sodium (see Tables 1 4).

Table 1: Drugs That May Decrease T3 Absorption (Hypothyroidism)

Potential impact: Concurrent use may reduce the efficacy of liothyronine sodium by binding and delaying or preventing absorption, potentially resulting in hypothyroidism.
Drug or Drug Class	Effect
Bile Acid Sequestrants -Colesevelam -Cholestyramine -Colestipol Ion Exchange Resins -Kayexalate -Sevelamer	Bile acid sequestrants and ion exchange resins are known to decrease thyroid hormones absorption. Administer liothyronine sodium at least 4 hours prior to these drugs or monitor TSH levels.

Table 2: Drugs That May Alter Triiodothyronine (T3) Serum Transport Without Affecting Free Thyroxine (FT4) Concentration (Euthyroidism)

Drug or Drug Class	Effect
Clofibrate Estrogen-containing oral contraceptives Estrogens (oral) Heroin/Methadone 5-Fluorouracil Mitotane Tamoxifen	These drugs may increase serum thyroxine-binding globulin (TBG) concentration.
Androgens/Anabolic Steroids Asparaginase Glucocorticoids Slow-Release Nicotinic Acid	These drugs may decrease serum TBG concentration.
Salicylates (>2 g/day)	Salicylates inhibit binding of T4 and T3 to TBG and transthyretin. An initial increase in serum FT4 is followed by return of FT4 to normal levels with sustained therapeutic serum salicylate concentrations, although total T4 levels may decrease by as much as 30%.
Other drugs: Carbamazepine Furosemide (>80 mg IV) Heparin Hydantoins Non-Steroidal Anti-inflammatory Drugs Fenamates	These drugs may cause protein binding site displacement. Furosemide has been shown to inhibit the protein binding of T4 to TBG and albumin, causing an increased free-T4 fraction in serum. Furosemide competes for T4-binding sites on TBG, prealbumin, and albumin, so that a single high dose can acutely lower the total T4 level. Phenytoin and carbamazepine reduce serum protein binding of thyroid hormones, and total and FT4 may be reduced by 20% to 40%, but most patients have normal serum TSH levels and are clinically euthyroid. Closely monitor thyroid hormone parameters.

Table 3: Drugs That May Alter Hepatic Metabolism of Thyroid hormones

Potential impact: Stimulation of hepatic microsomal drug-metabolizing enzyme activity may cause increased hepatic degradation of thyroid hormones, resulting in increased liothyronine sodium requirements.
Drug or Drug Class	Effect
Phenobarbital Rifampin	Phenobarbital has been shown to reduce the response to thyroxine. Phenobarbital increases L-thyroxine metabolism by inducing uridine 5'-diphospho-glucuronosyltransferase (UGT) and leads to a lower T4 serum levels. Changes in thyroid status may occur if barbiturates are added or withdrawn from patients being treated for hypothyroidism. Rifampin has been shown to accelerate the metabolism of thyroid hormones.

Table 4: Drugs That May Decrease Conversion of T4 to T3

Potential impact: Administration of these enzyme inhibitors decreases the peripheral conversion of T4 to T3, leading to decreased T3 levels. However, serum T4 levels are usually normal but may occasionally be slightly increased.
Drug or Drug Class	Effect
Beta-adrenergic antagonists (e.g., Propranolol >160 mg/day)	In patients treated with large doses of propranolol (>160 mg/day), T3 and T4 levels change, TSH levels remain normal, and patients are clinically euthyroid. Actions of particular beta-adrenergic antagonists may be impaired when a hypothyroid patient is converted to the euthyroid state.
Glucocorticoids (e.g., Dexamethasone 4 mg/day)	Short-term administration of large doses of glucocorticoids may decrease serum T3 concentrations by 30% with minimal change in serum T4 levels. However, long-term glucocorticoid therapy may result in slightly decreased T3 and T4 levels due to decreased TBG production (see above).
Other drugs: Amiodarone	Amiodarone inhibits peripheral conversion of levothyroxine (T4) to triiodothyronine (T3) and may cause isolated biochemical changes (increase in serum free-T4, and decreased or normal free-T3) in clinically euthyroid patients.

7.2 Antidiabetic Therapy

Addition of liothyronine sodium therapy in patients with diabetes mellitus may worsen glycemic control and result in increased antidiabetic agent or insulin requirements. Carefully monitor glycemic control, especially when liothyronine sodium is started, changed, or discontinued [see Warnings and Precautions (5.5)].

7.3 Oral Anticoagulants

Liothyronine sodium increases the response to oral anticoagulant therapy. Therefore, a decrease in the dose of anticoagulant may be warranted with correction of the hypothyroid state or when the liothyronine sodium dose is increased. Closely monitor coagulation tests to permit appropriate and timely dosage adjustments.

7.4 Digitalis Glycosides

Liothyronine sodium may reduce the therapeutic effects of digitalis glycosides. Serum digitalis glycoside levels may be decreased when a hypothyroid patient becomes euthyroid, necessitating an increase in the dose of digitalis glycosides.

7.5 Antidepressant Therapy

Concurrent use of tricyclic (e.g., amitriptyline) or tetracyclic (e.g., maprotiline) antidepressants and liothyronine sodium may increase the therapeutic and toxic effects of both drugs, possibly due to increased receptor sensitivity to catecholamines. Toxic effects may include increased risk of cardiac arrhythmias and central nervous system stimulation. Liothyronine sodium may accelerate the onset of action of tricyclics. Administration of sertraline in patients stabilized on liothyronine sodium may result in increased liothyronine sodium requirements.

7.6 Ketamine

Concurrent use of ketamine and liothyronine sodium may produce marked hypertension and tachycardia. Closely monitor blood pressure and heart rate in these patients.

7.7 Sympathomimetics

Concurrent use of sympathomimetics and liothyronine sodium may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.

7.8 Tyrosine-Kinase Inhibitors

Concurrent use of tyrosine-kinase inhibitors such as imatinib may cause hypothyroidism. Closely monitor TSH levels in such patients.

7.9 Drug-Laboratory Test Interactions

Consider changes in TBG concentration when interpreting T4 and T3 values. Measure and evaluate unbound (free) hormone in this circumstance. Pregnancy, infectious hepatitis, estrogens, estrogen-containing oral contraceptives, and acute intermittent porphyria increase TBG concentrations. Nephrosis, severe hypoproteinemia, severe liver disease, acromegaly, androgens and corticosteroids decrease TBG concentration. Familial hyper- or hypo-thyroxine binding globulinemias have been described, with the incidence of TBG deficiency approximating 1 in 9000.

8 Use In Specific Populations ⮝

8.1 Pregnancy

Risk Summary

Experience with liothyronine use in pregnant women, including data from post-marketing studies, have not reported increased rates of major birth defects or miscarriages (see Data). There are risks to the mother and fetus associated with untreated hypothyroidism in pregnancy. Since TSH levels may increase during pregnancy, TSH should be monitored and liothyronine sodium dosage adjusted during pregnancy (see Clinical Considerations). There are no animal studies conducted with liothyronine during pregnancy. Liothyronine sodium should not be discontinued during pregnancy and hypothyroidism diagnosed during pregnancy should be promptly treated.

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

Clinical Considerations

Disease-associated maternal and/or embryo/fetal risk

Maternal hypothyroidism during pregnancy is associated with a higher rate of complications, including spontaneous abortion, gestational hypertension, pre-eclampsia, stillbirth, and premature delivery. Untreated maternal hypothyroidism may have an adverse effect on fetal neurocognitive development.

Dose adjustments during pregnancy and the postpartum period

Pregnancy may increase liothyronine sodium requirements. Serum TSH levels should be monitored and the liothyronine sodium dosage adjusted during pregnancy. Since postpartum TSH levels are similar to preconception values, the liothyronine sodium dosage should return to the pre-pregnancy dose immediately after delivery [see Dosage and Administration (2.3)].

Data

Human Data

Liothyronine is approved for use as a replacement therapy for hypothyroidism. Data from post-marketing studies have not reported increased rates of fetal malformations, miscarriages, or other adverse maternal or fetal outcomes associated with liothyronine use in pregnant women.

8.2 Lactation

Risk Summary

Limited published studies report that liothyronine is present in human milk. However, there is insufficient information to determine the effects of liothyronine on the breastfed infant and no available information on the effects of liothyronine on milk production. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for liothyronine sodium and any potential adverse effects on the breastfed infant from liothyronine sodium or from the underlying maternal condition.

8.4 Pediatric Use

The initial dose of liothyronine sodium varies with age and body weight. Dosing adjustments are based on an assessment of the individual patient's clinical and laboratory parameters [see Dosage and Administration (2.3, 2.4)].

In pediatric patients in whom a diagnosis of permanent hypothyroidism has not been established, discontinue thyroid hormone for a trial period, but only after the child is at least 3 years of age. Obtain serum TSH, T4, and T3 levels at the end of the trial period, and use laboratory test results and clinical assessments to guide diagnosis and treatment, if warranted [see Dosage and Administration (2.6)].

Congenital Hypothyroidism [see Dosage and Administration (2.2, 2.6)]

Rapid restoration of normal serum T4 concentrations is essential for preventing the adverse effects of congenital hypothyroidism on intellectual development as well as on overall physical growth and maturation. Therefore, initiate thyroid hormone immediately upon diagnosis. Thyroid hormone is generally continued for life in these patients.

Closely monitor infants during the first 2 weeks of thyroid hormone therapy for cardiac overload, arrhythmias, and aspiration from avid suckling.

Closely monitor patients to avoid undertreatment or overtreatment. Undertreatment may have deleterious effects on intellectual development and linear growth. Overtreatment is associated with craniosynostosis in infants, may adversely affect the tempo of brain maturation, and may accelerate the bone age and result in premature epiphyseal closure and compromised adult stature [see Dosage and Administration (2.6) and Adverse Reactions (6)].

Acquired Hypothyroidism in Pediatric Patients

Closely monitor patients to avoid undertreatment and overtreatment. Undertreatment may result in poor school performance due to impaired concentration and slowed mentation and in reduced adult height. Overtreatment may accelerate the bone age and result in premature epiphyseal closure and compromised adult stature.

Treated children may manifest a period of catch-up growth, which may be adequate in some cases to normalize adult height. In children with severe or prolonged hypothyroidism, catch-up growth may not be adequate to normalize adult height [see Adverse Reactions (6)].

8.5 Geriatric Use

Because of the increased prevalence of cardiovascular disease among the elderly, initiate liothyronine sodium at less than the full replacement dose [see Dosage and Administration (2.3) and Warnings and Precautions (5.1)]. Atrial arrhythmias can occur in elderly patients. Atrial fibrillation is the most common of the arrhythmias observed with thyroid hormone overtreatment in the elderly.

10 Overdosage ⮝

The signs and symptoms of overdosage are those of hyperthyroidism [see Warnings and Precautions (5.4) and Adverse Reactions (6)]. In addition, confusion and disorientation may occur. Cerebral embolism, seizure, shock, coma, and death have been reported. Symptoms may not necessarily be evident or may not appear until several days after ingestion.

Reduce the liothyronine sodium dose or temporarily discontinued 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.

11 Description ⮝

Liothyronine sodium tablets contain the active ingredient, liothyronine (L-triiodothyronine or LT3), a synthetic form of a thyroid hormone liothyronine in sodium salt form. It is chemically designated as L-Tyrosine, O-(4-hydroxy-3-iodophenyl)-3,5-diiodo-, monosodium salt. The molecular formula, molecular weight and structural formula of liothyronine sodium are given below.

C15H11I3NNaO4 M.W.672.96

Liothyronine sodium tablets contain liothyronine sodium equivalent to liothyronine in 5 mcg, 25 mcg, and 50 mcg. Inactive ingredients consist of calcium sulfate, corn starch, gelatin, stearic acid, sucrose and talc.

12 Clinical Pharmacology ⮝

12.1 Mechanism of Action

Thyroid hormones exert their physiologic actions through control of DNA transcription and protein synthesis. Triiodothyronine (T3) and L-thyroxine (T4) diffuse into the cell nucleus and bind to thyroid receptor proteins attached to DNA. This hormone nuclear receptor complex activates gene transcription and synthesis of messenger RNA and cytoplasmic proteins.

The physiological actions of thyroid hormones are produced predominantly by T3, the majority of which (approximately 80%) is derived from T4 by deiodination in peripheral tissues.

12.2 Pharmacodynamics

The onset of activity of liothyronine sodium occurs within a few hours. Maximum pharmacologic response occurs within 2 or 3 days.

12.3 Pharmacokinetics

Absorption

T3 is almost totally absorbed, 95 percent in 4 hours. The hormones contained in the natural preparations are absorbed in a manner similar to the synthetic hormones.

Distribution

Liothyronine sodium (T3) is not firmly bound to serum protein. The higher affinity of levothyroxine (T4) for both thyroid-binding globulin and thyroid-binding prealbumin as compared to triiodothyronine (T3) partially explains the higher serum levels and longer half-life of the former hormone. Both protein-bound hormones exist in reverse equilibrium with minute amounts of free hormone, the latter accounting for the metabolic activity.

Elimination

Metabolism

The major pathway of thyroid hormone metabolism is through sequential deiodination. Approximately 80% of circulating T3 is derived from peripheral T4 by monodeiodination. The liver is the major site of degradation for both T4 and T3. T3 is further deiodinated to diiodothyronine. Thyroid hormones are also metabolized via conjugation with glucuronides and sulfates and excreted directly into the bile and gut where they undergo enterohepatic recirculation.

Excretion

Thyroid hormones are primarily eliminated by the kidneys. A portion of the conjugated hormone reaches the colon unchanged and is eliminated in the feces. The biological half-life is about 2-1/2 days.

13 Nonclinical Toxicology ⮝

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Animal studies have not been performed to evaluate the carcinogenic potential, mutagenic potential or effects on fertility of liothyronine sodium.

16 How Supplied/storage And Handling ⮝

Liothyronine sodium tablets (round, white to off-white) are supplied as follows:

Strength	Tablet Markings	NDC bottles of 100
5 mcg	Debossed with KPI on one side and 115 on the other side	59762-1206-1
25 mcg	Scored on one side and debossed with KPI and 116 on the other side	59762-1207-1
50 mcg	Scored on one side and debossed with KPI and 117 on the other side	59762-1208-1

Store between 15 C and 30 C (59 F and 86 F).

Liothyronine Sodium Tablets, Usp 50 Mcg- 90 Tablets Container Label ⮝

LIOTHYRONINE SODIUM liothyronine sodium tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:42291-417(NDC:42794-018) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LIOTHYRONINE SODIUM (UNII: GCA9VV7D2N) (LIOTHYRONINE - UNII:06LU7C9H1V) LIOTHYRONINE 5 ug

Inactive Ingredients Ingredient Name Strength CALCIUM SULFATE DIHYDRATE (UNII: 4846Q921YM) STARCH, CORN (UNII: O8232NY3SJ) GELATIN (UNII: 2G86QN327L) MAGNESIUM STEARATE (UNII: 70097M6I30) MANNITOL (UNII: 3OWL53L36A)

Product Characteristics Color white (white to off-white) Score no score Shape ROUND Size 6mm Flavor Imprint Code 18 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:42291-417-90 90 in 1 BOTTLE; Type 0: Not a Combination Product 10/11/2018

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA200295 10/11/2018

LIOTHYRONINE SODIUM liothyronine sodium tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:42291-418(NDC:42794-019) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LIOTHYRONINE SODIUM (UNII: GCA9VV7D2N) (LIOTHYRONINE - UNII:06LU7C9H1V) LIOTHYRONINE 25 ug

Inactive Ingredients Ingredient Name Strength CALCIUM SULFATE DIHYDRATE (UNII: 4846Q921YM) STARCH, CORN (UNII: O8232NY3SJ) GELATIN (UNII: 2G86QN327L) MAGNESIUM STEARATE (UNII: 70097M6I30) MANNITOL (UNII: 3OWL53L36A)

Product Characteristics Color white (white to off-white) Score 2 pieces Shape ROUND Size 7mm Flavor Imprint Code 19 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:42291-418-90 90 in 1 BOTTLE; Type 0: Not a Combination Product 10/11/2018

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA200295 10/11/2018

LIOTHYRONINE SODIUM liothyronine sodium tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:42291-419(NDC:42794-020) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LIOTHYRONINE SODIUM (UNII: GCA9VV7D2N) (LIOTHYRONINE - UNII:06LU7C9H1V) LIOTHYRONINE 50 ug

Product Characteristics Color white (white to off-white) Score 2 pieces Shape ROUND Size 8mm Flavor Imprint Code 20 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:42291-419-90 90 in 1 BOTTLE; Type 0: Not a Combination Product 10/11/2018

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA200295 10/11/2018

Labeler - AvKARE, Inc (796560394)

Revised: 8/2019 Document Id: 90a35e48-2c7d-6669-e053-2a95a90a1bff 34391-3 Set id: 77f9f96f-7895-723b-e053-2a91aa0a0d59 Version: 2 Effective Time: 20190821 AvKARE, Inc

No Title 1572455335 ⮝

Drugs with thyroid hormone activity, alone or together with other therapeutic agents, have been used for the treatment of obesity. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.

Liothyronine Sodium Tablets, Usp 5 Mcg ⮝

Liothyronine Sodium Tablets, USP 5 mcg Container Label

Repackaged by:
Aidarex Pharmaceuticals, LLC
Corona, CA 92880

NDC 53217-0361

Sigmapharm Laboratories, LLC

Liothyronine Sodium Tablets, USP

5 mcg

Rx Only

53217-0361_LIOTHYRONINE-SOD_5McG

LIOTHYRONINE SODIUM liothyronine sodium tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:53217-361(NDC:42794-018) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LIOTHYRONINE SODIUM (UNII: GCA9VV7D2N) (LIOTHYRONINE - UNII:06LU7C9H1V) LIOTHYRONINE 5 ug

Inactive Ingredients Ingredient Name Strength CALCIUM SULFATE DIHYDRATE (UNII: 4846Q921YM) STARCH, CORN (UNII: O8232NY3SJ) GELATIN (UNII: 2G86QN327L) MAGNESIUM STEARATE (UNII: 70097M6I30) MANNITOL (UNII: 3OWL53L36A)

Product Characteristics Color WHITE (white to off-white) Score no score Shape ROUND Size 6mm Flavor Imprint Code 18 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:53217-361-30 30 in 1 BOTTLE; Type 0: Not a Combination Product 01/11/2018

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA200295 01/11/2018

Labeler - Aidarex Pharmaceuticals LLC (801503249)

Revised: 8/2018 Document Id: 4851a1c6-ffc2-45fe-a849-4e8c4c5eca3c 34391-3 Set id: 818ae20e-9909-41ec-a0a9-4b6e9e86e794 Version: 1 Effective Time: 20180820 Aidarex Pharmaceuticals LLC

No Title 1572456733 ⮝

Drugs with thyroid hormone activity, alone or together with other therapeutic agents, have been used for the treatment of obesity. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.

Liothyronine Sodium 5mcg ⮝

Drugs with thyroid hormone activity, alone or together with other therapeutic agents, have been used for the treatment of obesity. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.

WARNINGS

Drugs with thyroid hormone activity, alone or together with other therapeutic agents, have been used for the treatment of obesity. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.

Thyroid hormone drugs are natural or synthetic preparations containing tetraiodothyronine (T4, levothyroxine) sodium or triiodothyronine (T3, liothyronine) sodium or both. T4 and T3 are produced in the human thyroid gland by the iodination and coupling of the amino acid tyrosine. T4 contains four iodine atoms and is formed by the coupling of two molecules of diiodotyrosine (DIT). T3 contains three atoms of iodine and is formed by the coupling of one molecule of DIT with one molecule of monoiodotyrosine (MIT). Both hormones are stored in the thyroid colloid as thyroglobulin.

Thyroid hormone preparations belong to two categories: (1) natural hormonal preparations derived from animal thyroid, and (2) synthetic preparations. Natural preparations include desiccated thyroid and thyroglobulin. Desiccated thyroid is derived from domesticated animals that are used for food by man (either beef or hog thyroid), and thyroglobulin is derived from thyroid glands of the hog. The United States Pharmacopeia (USP) has standardized the total iodine content of natural preparations. Thyroid USP contains not less than (NLT) 0.17 percent and not more than (NMT) 0.23 percent iodine, and thyroglobulin contains not less than (NLT) 0.7 percent of organically bound iodine. Iodine content is only an indirect indicator of true hormonal biologic activity.

Liothyronine Sodium Tablets, USP contain liothyronine (L-triiodothyronine or LT3), a synthetic form of a natural thyroid hormone, and is available as the sodium salt.

The structural and empirical formulas and molecular weight of liothyronine sodium are given below.

[Chemical Structure]

Twenty-five mcg of liothyronine is equivalent to approximately 1 grain of desiccated thyroid or thyroglobulin and 0.1 mg of L-thyroxine.

Each round, white Liothyronine Sodium Tablet, USP contains liothyronine sodium equivalent to liothyronine as follows: 5 mcg debossed 5 and 220; 25 mcg scored and debossed 25 and 222; 50 mcg scored and debossed 50 and 223. Inactive ingredients consist of calcium sulfate, microcrystalline cellulose, hypromellose, talc, and colloidal silicon dioxide.

The mechanisms by which thyroid hormones exert their physiologic action are not well understood. These hormones enhance oxygen consumption by most tissues of the body, increase the basal metabolic rate and the metabolism of carbohydrates, lipids and proteins. Thus, they exert a profound influence on every organ system in the body and are of particular importance in the development of the central nervous system.

Pharmacokinetics

Since liothyronine sodium (T3) is not firmly bound to serum protein, it is readily available to body tissues. The onset of activity of liothyronine sodium is rapid, occurring within a few hours. Maximum pharmacologic response occurs within 2 or 3 days, providing early clinical response. The biological half-life is about 2-1/2 days.

T3 is almost totally absorbed, 95 percent in 4 hours. The hormones contained in the natural preparations are absorbed in a manner similar to the synthetic hormones.

Liothyronine sodium has a rapid cutoff of activity which permits quick dosage adjustment and facilitates control of the effects of overdosage, should they occur.

The higher affinity of levothyroxine (T4) for both thyroid-binding globulin and thyroid-binding prealbumin as compared to triiodothyronine (T3) partially explains the higher serum levels and longer half-life of the former hormone. Both protein-bound hormones exist in reverse equilibrium with minute amounts of free hormone, the latter accounting for the metabolic activity.

Thyroid hormone drugs are indicated:

As replacement or supplemental therapy in patients with hypothyroidism of any etiology, except transient hypothyroidism during the recovery phase of subacute thyroiditis. This category includes cretinism, myxedema and ordinary hypothyroidism in patients of any age (pediatric patients, adults, the elderly), or state (including pregnancy); primary hypothyroidism resulting from functional deficiency, primary atrophy, partial or total absence of thyroid gland, or the effects of surgery, radiation, or drugs, with or without the presence of goiter; and secondary (pituitary) or tertiary (hypothalamic) hypothyroidism (see WARNINGS).
As pituitary thyroid-stimulating hormone (TSH) suppressants, in the treatment or prevention of various types of euthyroid goiters, including thyroid nodules, subacute or chronic lymphocytic thyroiditis (Hashimoto's) and multinodular goiter.
As diagnostic agents in suppression tests to differentiate suspected mild hyperthyroidism or thyroid gland autonomy.

Liothyronine Sodium Tablets, USP can be used in patients allergic to desiccated thyroid or thyroid extract derived from pork or beef.

Thyroid hormone preparations are generally contraindicated in patients with diagnosed but as yet uncorrected adrenal cortical insufficiency, untreated thyrotoxicosis and apparent hypersensitivity to any of their active or extraneous constituents. There is no well-documented evidence from the literature, however, of true allergic or idiosyncratic reactions to thyroid hormone.

The use of thyroid hormones in the therapy of obesity, alone or combined with other drugs, is unjustified and has been shown to be ineffective. Neither is their use justified for the treatment of male or female infertility unless this condition is accompanied by hypothyroidism.

Thyroid hormones should be used with great caution in a number of circumstances where the integrity of the cardiovascular system, particularly the coronary arteries, is suspected. These include patients with angina pectoris or the elderly, in whom there is a greater likelihood of occult cardiac disease. In these patients, liothyronine sodium therapy should be initiated with low doses, with due consideration for its relatively rapid onset of action. Starting dosage of Liothyronine Sodium Tablets, USP is 5 mcg daily, and should be increased by no more than 5 mcg increments at 2-week intervals. When, in such patients, a euthyroid state can only be reached at the expense of an aggravation of the cardiovascular disease, thyroid hormone dosage should be reduced.

Morphologic hypogonadism and nephrosis should be ruled out before the drug is administered. If hypopituitarism is present, the adrenal deficiency must be corrected prior to starting the drug.

Myxedematous patients are very sensitive to thyroid; dosage should be started at a very low level and increased gradually.

Severe and prolonged hypothyroidism can lead to a decreased level of adrenocortical activity commensurate with the lowered metabolic state. When thyroid-replacement therapy is administered, the metabolism increases at a greater rate than adrenocortical activity. This can precipitate adrenocortical insufficiency. Therefore, in severe and prolonged hypothyroidism, supplemental adrenocortical steroids may be necessary. In rare instances the administration of thyroid hormone may precipitate a hyperthyroid state or may aggravate existing hyperthyroidism.

General

Thyroid hormone therapy in patients with concomitant diabetes mellitus or insipidus or adrenal cortical insufficiency aggravates the intensity of their symptoms. Appropriate adjustments of the various therapeutic measures directed at these concomitant endocrine diseases are required.

The therapy of myxedema coma requires simultaneous administration of glucocorticoids.

Hypothyroidism decreases and hyperthyroidism increases the sensitivity to oral anticoagulants. Prothrombin time should be closely monitored in thyroid-treated patients on oral anticoagulants and dosage of the latter agents adjusted on the basis of frequent prothrombin time determinations. In infants, excessive doses of thyroid hormone preparations may produce craniosynostosis.

Information for the Patient

Patients on thyroid hormone preparations and parents of pediatric patients on thyroid therapy should be informed that:

Replacement therapy is to be taken essentially for life, with the exception of cases of transient hypothyroidism, usually associated with thyroiditis, and in those patients receiving a therapeutic trial of the drug.
They should immediately report during the course of therapy any signs or symptoms of thyroid hormone toxicity, e.g., chest pain, increased pulse rate, palpitations, excessive sweating, heat intolerance, nervousness, or any other unusual event.
In case of concomitant diabetes mellitus, the daily dosage of antidiabetic medication may need readjustment as thyroid hormone replacement is achieved. If thyroid medication is stopped, a downward readjustment of the dosage of insulin or oral hypoglycemic agent may be necessary to avoid hypoglycemia. At all times, close monitoring of urinary glucose levels is mandatory in such patients.
In case of concomitant oral anticoagulant therapy, the prothrombin time should be measured frequently to determine if the dosage of oral anticoagulants is to be readjusted.
Partial loss of hair may be experienced by pediatric patients in the first few months of thyroid therapy, but this is usually a transient phenomenon and later recovery is usually the rule.

Laboratory Tests

Treatment of patients with thyroid hormones requires the periodic assessment of thyroid status by means of appropriate laboratory tests besides the full clinical evaluation. The TSH suppression test can be used to test the effectiveness of any thyroid preparation, bearing in mind the relative insensitivity of the infant pituitary to the negative feedback effect of thyroid hormones. Serum T4 levels can be used to test the effectiveness of all thyroid medications except products containing liothyronine sodium. When the total serum T4 is low but TSH is normal, a test specific to assess unbound (free) T4 levels is warranted. Specific measurements of T4 and T3 by competitive protein binding or radioimmunoassay are not influenced by blood levels of organic or inorganic iodine and have essentially replaced older tests of thyroid hormone measurements, i.e., PBI, BEI and T4 by column.

Drug Interactions

Oral Anticoagulants

Thyroid hormones appear to increase catabolism of vitamin K-dependent clotting factors. If oral anticoagulants are also being given, compensatory increases in clotting factor synthesis are impaired. Patients stabilized on oral anticoagulants who are found to require thyroid replacement therapy should be watched very closely when thyroid is started. If a patient is truly hypothyroid, it is likely that a reduction in anticoagulant dosage will be required. No special precautions appear to be necessary when oral anticoagulant therapy is begun in a patient already stabilized on maintenance thyroid replacement therapy.

Insulin or Oral Hypoglycemics

Initiating thyroid replacement therapy may cause increases in insulin or oral hypoglycemic requirements. The effects seen are poorly understood and depend upon a variety of factors such as dose and type of thyroid preparations and endocrine status of the patient. Patients receiving insulin or oral hypoglycemics should be closely watched during initiation of thyroid replacement therapy.

Cholestyramine

Cholestyramine binds both T4 and T3 in the intestine, thus impairing absorption of these thyroid hormones. In vitro studies indicate that the binding is not easily removed. Therefore, 4 to 5 hours should elapse between administration of cholestyramine and thyroid hormones.

Estrogen, Oral Contraceptives

Estrogens tend to increase serum thyroxine-binding globulin (TBg). In a patient with a nonfunctioning thyroid gland who is receiving thyroid replacement therapy, free levothyroxine may be decreased when estrogens are started thus increasing thyroid requirements. However, if the patient's thyroid gland has sufficient function, the decreased free thyroxine will result in a compensatory increase in thyroxine output by the thyroid. Therefore, patients without a functioning thyroid gland who are on thyroid replacement therapy may need to increase their thyroid dose if estrogens or estrogen-containing oral contraceptives are given.

Tricyclic Antidepressants

Use of thyroid products with imipramine and other tricyclic antidepressants may increase receptor sensitivity and enhance antidepressant activity; transient cardiac arrhythmias have been observed. Thyroid hormone activity may also be enhanced.

Digitalis

Thyroid preparations may potentiate the toxic effects of digitalis. Thyroid hormonal replacement increases metabolic rate, which requires an increase in digitalis dosage.

Ketamine

When administered to patients on a thyroid preparation, this parenteral anesthetic may cause hypertension and tachycardia. Use with caution and be prepared to treat hypertension, if necessary.

Vasopressors

Thyroxine increases the adrenergic effect of catecholamines such as epinephrine and norepinephrine. Therefore, injection of these agents into patients receiving thyroid preparations increases the risk of precipitating coronary insufficiency, especially in patients with coronary artery disease. Careful observation is required.

Drug/Laboratory Test Interactions

The following drugs or moieties are known to interfere with laboratory tests performed in patients on thyroid hormone therapy: androgens, corticosteroids, estrogens, oral contraceptives containing estrogens, iodine-containing preparations and the numerous preparations containing salicylates.

Changes in TBg concentration should be taken into consideration in the interpretation of T4 and T3values. In such cases, the unbound (free) hormone should be measured. Pregnancy, estrogens and estrogen-containing oral contraceptives increase TBg concentrations. TBg may also be increased during infectious hepatitis. Decreases in TBg concentrations are observed in nephrosis, acromegaly and after androgen or corticosteroid therapy. Familial hyper- or hypo-thyroxine-binding-globulinemias have been described. The incidence of TBg deficiency approximates 1 in 9000. The binding of thyroxine by thyroxine-binding prealbumin (TBPA) is inhibited by salicylates.
Medicinal or dietary iodine interferes with all in vivo tests of radioiodine uptake, producing low uptakes which may not be reflective of a true decrease in hormone synthesis.
The persistence of clinical and laboratory evidence of hypothyroidism in spite of adequate dosage replacement indicates either poor patient compliance, poor absorption, excessive fecal loss, or inactivity of the preparation. Intracellular resistance to thyroid hormone is quite rare.

Carcinogenesis, Mutagenesis and Impairment of Fertility

A reportedly apparent association between prolonged thyroid therapy and breast cancer has not been confirmed and patients on thyroid for established indications should not discontinue therapy. No confirmatory long-term studies in animals have been performed to evaluate carcinogenic potential, mutagenicity, or impairment of fertility in either males or females.

Pregnancy

Category A

Thyroid hormones do not readily cross the placental barrier. The clinical experience to date does not indicate any adverse effect on fetuses when thyroid hormones are administered to pregnant women. On the basis of current knowledge, thyroid replacement therapy to hypothyroid women should not be discontinued during pregnancy.

Nursing Mothers

Minimal amounts of thyroid hormones are excreted in human milk. Thyroid is not associated with serious adverse reactions and does not have a known tumorigenic potential. However, caution should be exercised when thyroid is administered to a nursing woman.

Geriatric Use

Clinical studies of liothyronine sodium did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Pediatric Use

Pregnant mothers provide little or no thyroid hormone to the fetus. The incidence of congenital hypothyroidism is relatively high (1:4000) and the hypothyroid fetus would not derive any benefit from the small amounts of hormone crossing the placental barrier. Routine determinations of serum T4and/or TSH is strongly advised in neonates in view of the deleterious effects of thyroid deficiency on growth and development.

Treatment should be initiated immediately upon diagnosis and maintained for life, unless transient hypothyroidism is suspected, in which case, therapy may be interrupted for 2 to 8 weeks after the age of 3 years to reassess the condition. Cessation of therapy is justified in patients who have maintained a normal TSH during those 2 to 8 weeks.

Adverse reactions, other than those indicative of hyperthyroidism because of therapeutic overdosage, either initially or during the maintenance period are rare (see OVERDOSAGE).

In rare instances, allergic skin reactions have been reported with Liothyronine Sodium Tablets, USP.

Signs and Symptoms

Headache, irritability, nervousness, sweating, arrhythmia (including tachycardia), increased bowel motility and menstrual irregularities. Angina pectoris or congestive heart failure may be induced or aggravated. Shock may also develop. Massive overdosage may result in symptoms resembling thyroid storm. Chronic excessive dosage will produce the signs and symptoms of hyperthyroidism.

Treatment Of Overdosage

Dosage should be reduced or therapy temporarily discontinued if signs and symptoms of overdosage appear. Treatment may be reinstituted at a lower dosage. In normal individuals, normal hypothalamic-pituitary-thyroid axis function is restored in 6 to 8 weeks after thyroid suppression.

Treatment of acute massive thyroid hormone overdosage is aimed at reducing gastrointestinal absorption of the drugs and counteracting central and peripheral effects, mainly those of increased sympathetic activity. Vomiting may be induced initially if further gastrointestinal absorption can reasonably be prevented and barring contraindications such as coma, convulsions, or loss of the gagging reflex. Treatment is symptomatic and supportive. Oxygen may be administered and ventilation maintained. Cardiac glycosides may be indicated if congestive heart failure develops. Measures to control fever, hypoglycemia, or fluid loss should be instituted if needed. Antiadrenergic agents, particularly propranolol, have been used advantageously in the treatment of increased sympathetic activity. Propranolol may be administered intravenously at a dosage of 1 to 3 mg over a 10-minute period or orally, 80 to 160 mg/day, especially when no contraindications exist for its use.

The dosage of thyroid hormones is determined by the indication and must in every case be individualized according to patient response and laboratory findings.

Liothyronine Sodium Tablets, USP are intended for oral administration; once-a-day dosage is recommended. Although liothyronine sodium has a rapid cutoff, its metabolic effects persist for a few days following discontinuance.

Mild Hypothyroidism

Recommended starting dosage is 25 mcg daily. Daily dosage then may be increased by up to 25 mcg every 1 or 2 weeks. Usual maintenance dose is 25 to 75 mcg daily.

The rapid onset and dissipation of action of liothyronine sodium (T3), as compared with levothyroxine sodium (T4), has led some clinicians to prefer its use in patients who might be more susceptible to the untoward effects of thyroid medication. However, the wide swings in serum T3 levels that follow its administration and the possibility of more pronounced cardiovascular side effects tend to counterbalance the stated advantages.

Liothyronine Sodium Tablets, USP may be used in preference to levothyroxine (T4) during radioisotope scanning procedures, since induction of hypothyroidism in those cases is more abrupt and can be of shorter duration. It may also be preferred when impairment of peripheral conversion of T4 to T3 is suspected.

Myxedema

Recommended starting dosage is 5 mcg daily. This may be increased by 5 to 10 mcg daily every 1 or 2 weeks. When 25 mcg daily is reached, dosage may be increased by 5 to 25 mcg every 1 or 2 weeks until a satisfactory therapeutic response is attained. Usual maintenance dose is 50 to 100 mcg daily.

Myxedema Coma

Myxedema coma is usually precipitated in the hypothyroid patient of long standing by intercurrent illness or drugs such as sedatives and anesthetics and should be considered a medical emergency.

An intravenous preparation of liothyronine sodium is marketed under the trade name Triostat for use in myxedema coma/precoma.

Congenital Hypothyroidism

Recommended starting dosage is 5 mcg daily, with a 5 mcg increment every 3 to 4 days until the desired response is achieved. Infants a few months old may require only 20 mcg daily for maintenance. At 1 year, 50 mcg daily may be required. Above 3 years, full adult dosage may be necessary (see PRECAUTIONS, PEDIATRIC USE).

Simple (non-toxic) Goiter

Recommended starting dosage is 5 mcg daily. This dosage may be increased by 5 to 10 mcg daily every 1 or 2 weeks. When 25 mcg daily is reached, dosage may be increased every week or two by 12.5 or 25 mcg. Usual maintenance dosage is 75 mcg daily.

In the elderly or in pediatric patients, therapy should be started with 5 mcg daily and increased only by 5 mcg increments at the recommended intervals.

When switching a patient to Liothyronine Sodium Tablets, USP from thyroid, L-thyroxine or thyroglobulin, discontinue the other medication, initiate Liothyronine Sodium Tablets, USP at a low dosage, and increase gradually according to the patient's response. When selecting a starting dosage, bear in mind that this drug has a rapid onset of action, and that residual effects of the other thyroid preparation may persist for the first several weeks of therapy.

Thyroid Suppression Therapy

Administration of thyroid hormone in doses higher than those produced physiologically by the gland results in suppression of the production of endogenous hormone. This is the basis for the thyroid suppression test and is used as an aid in the diagnosis of patients with signs of mild hyperthyroidism in whom baseline laboratory tests appear normal or to demonstrate thyroid gland autonomy in patients with Graves' ophthalmopathy. 131I uptake is determined before and after the administration of the exogenous hormone. A 50% or greater suppression of uptake indicates a normal thyroid-pituitary axis and thus rules out thyroid gland autonomy.

Liothyronine Sodium Tablets, USP are given in doses of 75 to 100 mcg/day for 7 days, and radioactive iodine uptake is determined before and after administration of the hormone. If thyroid function is under normal control, the radioiodine uptake will drop significantly after treatment. Liothyronine Sodium Tablets, USP should be administered cautiously to patients in whom there is a strong suspicion of thyroid gland autonomy, in view of the fact that the exogenous hormone effects will be additive to the endogenous source.

Rx Only

Liothyronine Sodium Tablets, USP, 5 mcg, are white to off-white, round, flat, debossed "5" over "220" on one side and plain on the other

Liothyronine Sodium Tablets, USP, 25 mcg, are white to off-white, round, flat, debossed "25" above the score and "222" below the score on one side and plain on the other

Liothyronine Sodium Tablets, USP, 50 mcg, are white to off-white, round, flat, debossed "50" above the score and "223" below the score on one side and plain on the other

Store at 20 to 25 C (68 to 77 F)
[see USP Controlled Room Temperature]

LIOTHYRONINE SODIUM liothyronine sodium tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:61919-239(NDC:0574-0220) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LIOTHYRONINE SODIUM (UNII: GCA9VV7D2N) (LIOTHYRONINE - UNII:06LU7C9H1V) LIOTHYRONINE 5 ug

Inactive Ingredients Ingredient Name Strength TALC (UNII: 7SEV7J4R1U) SILICON DIOXIDE (UNII: ETJ7Z6XBU4) CELLULOSE, MICROCRYSTALLINE (UNII: OP1R32D61U) HYPROMELLOSES (UNII: 3NXW29V3WO) CALCIUM SULFATE, UNSPECIFIED FORM (UNII: WAT0DDB505)

Product Characteristics Color white Score no score Shape ROUND Size 7mm Flavor Imprint Code 5;220 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:61919-239-30 30 in 1 BOTTLE; Type 0: Not a Combination Product 10/30/2017

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA090097 10/30/2017

Labeler - DIRECT RX (079254320)

Registrant - DIRECT RX (079254320)

Establishment
Name	Address	ID/FEI	Business Operations
DIRECT RX		079254320	repack(61919-239)

Revised: 10/2017 Document Id: 5ccacb47-6349-6143-e053-2991aa0ac066 34391-3 Set id: 5ccacb47-6348-6143-e053-2991aa0ac066 Version: 1 Effective Time: 20171030 DIRECT RX

Package Label.principal Display Panel ⮝

NDC: 51655-641-52

MFG: 42794-019-02

Liothyronine Sodium 25 mcg

30 Tablets

Rx Only

Lot#

Exp. Date:

Each tablet contains liothyronine sodium equivalent to 25 mcg of liothyronine

Dosage: See prescriber's instructions.

Store between 59-86 degrees.

Keep out of the reach of children.

Medication guide is found at fda.gov/drugs/drugsafety/ucm085729

Mfg by Sigmapharm Laboratories, LLC Bensalem, PA 19020

Repackaged by Northwind Pharmaceuticals, Indianapolis, IN 46256

LIOTHYRONINE SODIUM liothyronine sodium tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:51655-641(NDC:42794-019) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LIOTHYRONINE SODIUM (UNII: GCA9VV7D2N) (LIOTHYRONINE - UNII:06LU7C9H1V) LIOTHYRONINE 25 ug

Product Characteristics Color white Score 2 pieces Shape ROUND Size 7mm Flavor Imprint Code 19 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:51655-641-52 30 in 1 BOTTLE, DISPENSING

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA200295 11/12/2014

Labeler - Northwind Pharmaceuticals, LLC (036986393)

Registrant - Northwind Pharmaceuticals, LLC (036986393)

Establishment
Name	Address	ID/FEI	Business Operations
Northwind Pharmaceuticals, LLC		036986393	repack(51655-641)

Revised: 11/2014 Document Id: 868fd6e1-2f35-441c-8a23-4d215a486c54 34391-3 Set id: 2efef22c-799a-4825-a0a6-7287ef01fdbd Version: 1 Effective Time: 20141112 Northwind Pharmaceuticals, LLC

No Title 1572457763 ⮝

Distributed by:
Paddock Laboratories, Inc.
Minneapolis, MN 55427

Repackaged By :
Aidarex Pharmaceuticals LLC,
Corona, CA 92880

Rev 11/2008

No Title 1572448756 ⮝

Drugs with thyroid hormone activity, alone or together with other therapeutic agents, have been used for the treatment of obesity. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.

Description ⮝

Thyroid hormone drugs are natural or synthetic preparations containing tetraiodothyronine (T4, levothyroxine) sodium or triiodothyronine (T3, liothyronine) sodium or both. T4 and T3 are produced in the human thyroid gland by the iodination and coupling of the amino acid tyrosine. T4 contains four iodine atoms and is formed by the coupling of two molecules of diiodotyrosine (DIT). T3 contains three atoms of iodine and is formed by the coupling of one molecule of DIT with one molecule of monoiodotyrosine (MIT). Both hormones are stored in the thyroid colloid as thyroglobulin.

Thyroid hormone preparations belong to two categories: (1) natural hormonal preparations derived from animal thyroid, and (2) synthetic preparations. Natural preparations include desiccated thyroid and thyroglobulin. Desiccated thyroid is derived from domesticated animals that are used for food by man (either beef or hog thyroid), and thyroglobulin is derived from thyroid glands of the hog. The United States Pharmacopeia (USP) has standardized the total iodine content of natural preparations. Thyroid USP contains not less than (NLT) 0.17 percent and not more than (NMT) 0.23 percent iodine, and thyroglobulin contains not less than (NLT) 0.7 percent of organically bound iodine. Iodine content is only an indirect indicator of true hormonal biologic activity.

Liothyronine sodium tablets contain liothyronine (L-triiodothyronine or LT3), a synthetic form of a natural thyroid hormone, and is available as the sodium salt.

L-Tyrosine, O-(4-hydroxy-3-iodophenyl)-3,5-diiodo-,monosodium salt

Twenty-five mcg liothyronine is equivalent to approximately 1 grain of desiccated thyroid or thyroglobulin and 0.1 mg of L-thyroxine.

Inactive ingredients consist of calcium sulfate dihydrate, corn starch, gelatin, magnesium stearate and mannitol.

Clinical Pharmacology ⮝

The mechanisms by which thyroid hormones exert their physiologic action are not well understood. These hormones enhance oxygen consumption by most tissues of the body, increase the basal metabolic rate and the metabolism of carbohydrates, lipids and proteins. Thus, they exert a profound influence on every organ system in the body and are of particular importance in the development of the central nervous system.

Pharmacokinetics

Since liothyronine sodium (T3) is not firmly bound to serum protein, it is readily available to body tissues. The onset of activity of liothyronine sodium is rapid, occurring within a few hours. Maximum pharmacologic response occurs within 2 or 3 days, providing early clinical response. The biological half-life is about 2-1/2 days.

T3 is almost totally absorbed, 95 percent in 4 hours. The hormones contained in the natural preparations are absorbed in a manner similar to the synthetic hormones.

Liothyronine sodium has a rapid cutoff of activity which permits quick dosage adjustment and facilitates control of the effects of overdosage, should they occur.

The higher affinity of levothyroxine (T4) for both thyroid-binding globulin and thyroid-binding prealbumin as compared to triiodothyronine (T3) partially explains the higher serum levels and longer half-life of the former hormone. Both protein-bound hormones exist in reverse equilibrium with minute amounts of free hormone, the latter accounting for the metabolic activity.

Warnings ⮝

Drugs with thyroid hormone activity, alone or together with other therapeutic agents, have been used for the treatment of obesity. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life-threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects.

The use of thyroid hormones in the therapy of obesity, alone or combined with other drugs, is unjustified and has been shown to be ineffective. Neither is their use justified for the treatment of male or female infertility unless this condition is accompanied by hypothyroidism.

Thyroid hormones should be used with great caution in a number of circumstances where the integrity of the cardiovascular system, particularly the coronary arteries, is suspected. These include patients with angina pectoris or the elderly, in whom there is a greater likelihood of occult cardiac disease. In these patients, liothyronine sodium therapy should be initiated with low doses, with due consideration for its relatively rapid onset of action. Starting dosage of liothyronine sodium tablets is 5 mcg daily, and should be increased by no more than 5 mcg increments at 2-week intervals. When, in such patients, a euthyroid state can only be reached at the expense of an aggravation of the cardiovascular disease, thyroid hormone dosage should be reduced.

Morphologic hypogonadism and nephrosis should be ruled out before the drug is administered. If hypopituitarism is present, the adrenal deficiency must be corrected prior to starting the drug.

Myxedematous patients are very sensitive to thyroid; dosage should be started at a very low level and increased gradually.

Severe and prolonged hypothyroidism can lead to a decreased level of adrenocortical activity commensurate with the lowered metabolic state. When thyroid-replacement therapy is administered, the metabolism increases at a greater rate than adrenocortical activity. This can precipitate adrenocortical insufficiency. Therefore, in severe and prolonged hypothyroidism, supplemental adrenocortical steroids may be necessary. In rare instances the administration of thyroid hormone may precipitate a hyperthyroid state or may aggravate existing hyperthyroidism.

Precautions ⮝

General - Thyroid hormone therapy in patients with concomitant diabetes mellitus or insipidus or adrenal cortical insufficiency aggravates the intensity of their symptoms. Appropriate adjustments of the various therapeutic measures directed at these concomitant endocrine diseases are required.

The therapy of myxedema coma requires simultaneous administration of glucocorticoids.

Hypothyroidism decreases and hyperthyroidism increases the sensitivity to oral anticoagulants. Prothrombin time should be closely monitored in thyroid-treated patients on oral anticoagulants and dosage of the latter agents adjusted on the basis of frequent prothrombin time determinations. In infants, excessive doses of thyroid hormone preparations may produce craniosynostosis.

Information for the Patient - Patients on thyroid hormone preparations and parents of pediatric patients on thyroid therapy should be informed that:

Replacement therapy is to be taken essentially for life, with the exception of cases of transient hypothyroidism, usually associated with thyroiditis, and in those patients receiving a therapeutic trial of the drug.
They should immediately report during the course of therapy any signs or symptoms of thyroid hormone toxicity, e.g., chest pain, increased pulse rate, palpitations, excessive sweating, heat intolerance, nervousness, or any other unusual event.
In case of concomitant diabetes mellitus, the daily dosage of antidiabetic medication may need readjustment as thyroid hormone replacement is achieved. If thyroid medication is stopped, a downward readjustment of the dosage of insulin or oral hypoglycemic agent may be necessary to avoid hypoglycemia. At all times, close monitoring of urinary glucose levels is mandatory in such patients.
In case of concomitant oral anticoagulant therapy, the prothrombin time should be measured frequently to determine if the dosage of oral anticoagulants is to be readjusted.
Partial loss of hair may be experienced by pediatric patients in the first few months of thyroid therapy, but this is usually a transient phenomenon and later recovery is usually the rule.

Laboratory Tests - Treatment of patients with thyroid hormones requires the periodic assessment of thyroid status by means of appropriate laboratory tests besides the full clinical evaluation. The TSH suppression test can be used to test the effectiveness of any thyroid preparation, bearing in mind the relative insensitivity of the infant pituitary to the negative feedback effect of thyroid hormones. Serum T4 levels can be used to test the effectiveness of all thyroid medications except products containing liothyronine sodium. When the total serum T4 is low but TSH is normal, a test specific to assess unbound (free) T4 levels is warranted. Specific measurements of T4 and T3 by competitive protein binding or radioimmunoassay are not influenced by blood levels of organic or inorganic iodine and have essentially replaced older tests of thyroid hormone measurements, i.e., PBI, BEI and T4 by column.

Drug Interactions

Oral Anticoagulants - Thyroid hormones appear to increase catabolism of vitamin K-dependent clotting factors. If oral anticoagulants are also being given, compensatory increases in clotting factor synthesis are impaired. Patients stabilized on oral anticoagulants who are found to require thyroid replacement therapy should be watched very closely when thyroid is started. If a patient is truly hypothyroid, it is likely that a reduction in anticoagulant dosage will be required. No special precautions appear to be necessary when oral anticoagulant therapy is begun in a patient already stabilized on maintenance thyroid replacement therapy.

Insulin or Oral Hypoglycemics - Initiating thyroid replacement therapy may cause increases in insulin or oral hypoglycemic requirements. The effects seen are poorly understood and depend upon a variety of factors such as dose and type of thyroid preparations and endocrine status of the patient. Patients receiving insulin or oral hypoglycemics should be closely watched during initiation of thyroid replacement therapy.

Cholestyramine - Cholestyramine binds both T4 and T3 in the intestine, thus impairing absorption of these thyroid hormones. In vitro studies indicate that the binding is not easily removed. Therefore, 4 to 5 hours should elapse between administration of cholestyramine and thyroid hormones.

Estrogen, Oral Contraceptives - Estrogens tend to increase serum thyroxine-binding globulin (TBg). In a patient with a nonfunctioning thyroid gland who is receiving thyroid replacement therapy, free levothyroxine may be decreased when estrogens are started thus increasing thyroid requirements. However, if the patient s thyroid gland has sufficient function, the decreased free thyroxine will result in a compensatory increase in thyroxine output by the thyroid. Therefore, patients without a functioning thyroid gland who are on thyroid replacement therapy may need to increase their thyroid dose if estrogens or estrogen-containing oral contraceptives are given.

Tricyclic Antidepressants - Use of thyroid products with imipramine and other tricyclic antidepressants may increase receptor sensitivity and enhance antidepressant activity; transient cardiac arrhythmias have been observed. Thyroid hormone activity may also be enhanced.

Digitalis - Thyroid preparations may potentiate the toxic effects of digitalis. Thyroid hormonal replacement increases metabolic rate, which requires an increase in digitalis dosage.

Ketamine - When administered to patients on a thyroid preparation, this parenteral anesthetic may cause hypertension and tachycardia. Use with caution and be prepared to treat hypertension, if necessary.

Vasopressors - Thyroxine increases the adrenergic effect of catecholamines such as epinephrine and norepinephrine. Therefore, injection of these agents into patients receiving thyroid preparations increases the risk of precipitating coronary insufficiency, especially in patients with coronary artery disease. Careful observation is required.

Drug/Laboratory Test Interactions - The following drugs or moieties are known to interfere with laboratory tests performed in patients on thyroid hormone therapy: androgens, corticosteroids, estrogens, oral contraceptives containing estrogens, iodine-containing preparations and the numerous preparations containing salicylates.

Changes in TBg concentration should be taken into consideration in the interpretation of T4 and T3 values. In such cases, the unbound (free) hormone should be measured. Pregnancy, estrogens and estrogen-containing oral contraceptives increase TBg concentrations. TBg may also be increased during infectious hepatitis. Decreases in TBg concentrations are observed in nephrosis, acromegaly and after androgen or corticosteroid therapy. Familial hyper- or hypothyroxine-binding-globulinemias have been described. The incidence of TBg deficiency approximates 1 in 9000. The binding of thyroxine by thyroxine-binding prealbumin (TBPA) is inhibited by salicylates.
Medicinal or dietary iodine interferes with all in vivo tests of radioiodine uptake, producing low uptakes which may not be reflective of a true decrease in hormone synthesis.
The persistence of clinical and laboratory evidence of hypothyroidism in spite of adequate dosage replacement indicates either poor patient compliance, poor absorption, excessive fecal loss, or inactivity of the preparation. Intracellular resistance to thyroid hormone is quite rare.

Carcinogenesis, Mutagenesis and Impairment of Fertility - A reportedly apparent association between prolonged thyroid therapy and breast cancer has not been confirmed and patients on thyroid for established indications should not discontinue therapy. No confirmatory long-term studies in animals have been performed to evaluate carcinogenic potential, mutagenicity, or impairment of fertility in either males or females.

Pregnancy - Category A. Thyroid hormones do not readily cross the placental barrier. The clinical experience to date does not indicate any adverse effect on fetuses when thyroid hormones are administered to pregnant women. On the basis of current knowledge, thyroid replacement therapy to hypothyroid women should not be discontinued during pregnancy.

Nursing Mothers - Minimal amounts of thyroid hormones are excreted in human milk. Thyroid is not associated with serious adverse reactions and does not have a known tumorigenic potential. However, caution should be exercised when thyroid is administered to a nursing woman.

Geriatric Use - Clinical studies of liothyronine sodium did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Pediatric Use - Pregnant mothers provide little or no thyroid hormone to the fetus. The incidence of congenital hypothyroidism is relatively high (1:4000) and the hypothyroid fetus would not derive any benefit from the small amounts of hormone crossing the placental barrier. Routine determinations of serum T4 and/or TSH is strongly advised in neonates in view of the deleterious effects of thyroid deficiency on growth and development.

Treatment should be initiated immediately upon diagnosis and maintained for life, unless transient hypothyroidism is suspected, in which case, therapy may be interrupted for 2 to 8 weeks after the age of 3 years to reassess the condition. Cessation of therapy is justified in patients who have maintained a normal TSH during those 2 to 8 weeks.

Overdosage ⮝

Signs and Symptoms - Headache, irritability, nervousness, sweating, arrhythmia (including tachycardia), increased bowel motility and menstrual irregularities. Angina pectoris or congestive heart failure may be induced or aggravated. Shock may also develop. Massive overdosage may result in symptoms resembling thyroid storm. Chronic excessive dosage will produce the signs and symptoms of hyperthyroidism.

Treatment Of Overdosage - Dosage should be reduced or therapy temporarily discontinued if signs and symptoms of overdosage appear. Treatment may be reinstituted at a lower dosage. In normal individuals, normal hypothalamic-pituitary-thyroid axis function is restored in 6 to 8 weeks after thyroid suppression.

Treatment of acute massive thyroid hormone overdosage is aimed at reducing gastrointestinal absorption of the drugs and counteracting central and peripheral effects, mainly those of increased sympathetic activity. Vomiting may be induced initially if further gastrointestinal absorption can reasonably be prevented and barring contraindications such as coma, convulsions, or loss of the gagging reflex. Treatment is symptomatic and supportive. Oxygen may be administered and ventilation maintained. Cardiac glycosides may be indicated if congestive heart failure develops. Measures to control fever, hypoglycemia, or fluid loss should be instituted if needed. Antiadrenergic agents, particularly propranolol, have been used advantageously in the treatment of increased sympathetic activity. Propranolol may be administered intravenously at a dosage of 1 to 3 mg over a 10-minute period or orally, 80 to 160 mg/day, especially when no contraindications exist for its use.

How Supplied ⮝

Each 5 mcg tablet contains liothyronine sodium equivalent to 5 mcg of liothyronine. Each 25 mcg tablet contains liothyronine sodium equivalent to 25 mcg of liothyronine. Each 50 mcg tablet contains liothyronine sodium equivalent to 50 mcg of liothyronine.

5 mcg - Round, white to off-white color tablets debossed on one side and 18 on the other side.

Store between 15 and 30 C (59 and 86 F).

Repackaged by
Aidarex Pharmaceuticals, LLC
Corona, CA 92880

Manufactured by:

Sigmapharm Laboratories, LLC

Bensalem, PA 19020

OS020-05 REV.0118

Storage ⮝

Store between 15 and 30 C (59 and 86 F). Manufactured by: Sigmapharm Laboratories, LLC Bensalem, PA 19020

Liothyronine Sodium ⮝

LIOTHYRONINE SODIUM liothyronine sodium tablet

Product Information Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:50090-3131(NDC:42794-018) Route of Administration ORAL

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength LIOTHYRONINE SODIUM (UNII: GCA9VV7D2N) (LIOTHYRONINE - UNII:06LU7C9H1V) LIOTHYRONINE 5 ug

Inactive Ingredients Ingredient Name Strength CALCIUM SULFATE DIHYDRATE (UNII: 4846Q921YM) STARCH, CORN (UNII: O8232NY3SJ) GELATIN, UNSPECIFIED (UNII: 2G86QN327L) MAGNESIUM STEARATE (UNII: 70097M6I30) MANNITOL (UNII: 3OWL53L36A)

Product Characteristics Color white (white to off-white) Score no score Shape ROUND Size 6mm Flavor Imprint Code 18 Contains

Packaging # Item Code Package Description Marketing Start Date Marketing End Date 1 NDC:50090-3131-0 100 in 1 BOTTLE; Type 0: Not a Combination Product 09/05/2017 2 NDC:50090-3131-1 90 in 1 BOTTLE; Type 0: Not a Combination Product 03/12/2018

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date ANDA ANDA200295 12/03/2012

Labeler - A-S Medication Solutions (830016429)

Establishment
Name	Address	ID/FEI	Business Operations
A-S Medication Solutions		830016429	RELABEL(50090-3131) , REPACK(50090-3131)

Revised: 7/2018 Document Id: 9f93052a-02bd-44a5-a384-a521f1abb842 34391-3 Set id: db65bcd8-e9c9-4095-9975-03be1f443823 Version: 6 Effective Time: 20180726 A-S Medication Solutions