Prescription Drug Name:

Levothyroxine Sodium Tablets, USP

ID:

5fdbfca5-67c9-358e-e053-2991aa0a4eb4

Code:

34391-3

DESCRIPTION


id: 5fdbfca5-67ad-358e-e053-2991aa0a4eb4
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3

Levothyroxine Sodium Tablets, USP contain synthetic crystalline L-3,3′,5,5′-tetraiodothyronine sodium salt [levothyroxine (T
4) sodium]. Synthetic T
4 is identical to that produced in the human thyroid gland. Levothyroxine (T
4) sodium has an empirical formula of C
15H
10I
4N NaO
4 • H
2O, molecular weight of 798.86 g/mol (anhydrous), and structural formula as shown:

CLINICAL PHARMACOLOGY


id: 5fdbfca5-67af-358e-e053-2991aa0a4eb4
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1

Thyroid hormone synthesis and secretion is regulated by the hypothalamic-pituitary-thyroid axis. Thyrotropin-releasing hormone (TRH) released from the hypothalamus stimulates secretion of thyrotropin-stimulating hormone, TSH, from the anterior pituitary. TSH, in turn, is the physiologic stimulus for the synthesis and secretion of thyroid hormones, L-thyroxine (T
4) and L-triiodothyronine (T
3), by the thyroid gland. Circulating serum T
3 and T
4 levels exert a feedback effect on both TRH and TSH secretion. When serum T
3 and T
4 levels increase, TRH and TSH secretion decrease. When thyroid hormone levels decrease, TRH and TSH secretion increase. The mechanisms by which thyroid hormones exert their physiologic actions are not completely understood, but it is thought that their principal effects are exerted through control of DNA transcription and protein synthesis. T
3 and T
4 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. Thyroid hormones regulate multiple metabolic processes and play an essential role in normal growth and development, and normal maturation of the central nervous system and bone. The metabolic actions of thyroid hormones include augmentation of cellular respiration and thermogenesis, as well as metabolism of proteins, carbohydrates and lipids. The protein anabolic effects of thyroid hormones are essential to normal growth and development. The physiologic actions of thyroid hormones are produced predominately by T
3, the majority of which (approximately 80%) is derived from T
4 by deiodination in peripheral tissues. Levothyroxine, at doses individualized according to patient response, is effective as replacement or supplemental therapy in hypothyroidism of any etiology, except transient hypothyroidism during the recovery phase of subacute thyroiditis. Levothyroxine is also effective in the suppression of pituitary TSH secretion in the treatment or prevention of various types of euthyroid goiters, including thyroid nodules, Hashimoto’s thyroiditis, multinodular goiter and, as adjunctive therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer (see
INDICATIONS AND USAGE, PRECAUTIONS, DOSAGE AND ADMINISTRATION ).

INDICATIONS AND USAGE


id: 5fdbfca5-67b1-358e-e053-2991aa0a4eb4
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9

Levothyroxine sodium is used for the following indications:
Hypothyroidism
 – As replacement or supplemental therapy in congenital or acquired hypothyroidism of any etiology, except transient hypothyroidism during the recovery phase of subacute thyroiditis. Specific indications include: primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) hypothyroidism and subclinical hypothyroidism. Primary hypothyroidism may result from functional deficiency, primary atrophy, partial or total congenital absence of the thyroid gland, or from the effects of surgery, radiation, or drugs, with or without the presence of goiter.
Pituitary TSH Suppression
 – In the treatment or prevention of various types of euthyroid goiters (see
WARNINGS and
PRECAUTIONS ), including thyroid nodules (see
WARNINGS and
PRECAUTIONS ), subacute or chronic Iymphocytic thyroiditis (Hashimoto’s thyroiditis), multinodular goiter (see
WARNINGS and
PRECAUTIONS ), and, as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer.

CONTRAINDICATIONS


id: 5fdbfca5-67b2-358e-e053-2991aa0a4eb4
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3

Levothyroxine is contraindicated in patients with untreated subclinical (suppressed serum TSH level with normal T
3 and T
4 levels) or overt thyrotoxicosis of any etiology and in patients with acute myocardial infarction. Levothyroxine is contraindicated in patients with uncorrected adrenal insufficiency since thyroid hormones may precipitate an acute adrenal crisis by increasing the metabolic clearance of glucocorticoids (see
PRECAUTIONS ). Levothyroxine Sodium Tablets, USP is contraindicated in patients with hypersensitivity to any of the inactive ingredients in Levothyroxine Sodium Tablets, USP. (See
DESCRIPTION, Inactive Ingredients ).

ADVERSE REACTIONS


id: 5fdbfca5-67c4-358e-e053-2991aa0a4eb4
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4

Adverse reactions associated with levothyroxine therapy are primarily those of hyperthyroidism due to therapeutic overdosage (see
PRECAUTIONS and
OVERDOSAGE ). 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;
Cardiovascular:
 palpitations, tachycardia, arrhythmias, increased pulse and blood pressure, heart failure, angina, myocardial infarction, cardiac arrest;
Respiratory:
 dyspnea;
Gastrointestinal:
 diarrhea, vomiting, abdominal cramps and elevation in liver function tests;
Dermatologic:
 hair loss; flushing;
Endocrine:
 decreased bone mineral density;
Reproductive:
 menstrual irregularities, impaired fertility. Pseudotumor cerebri and slipped capital femoral epiphysis have been reported in children receiving levothyroxine therapy. Overtreatment may result in craniosynostosis in infants and premature closure of the epiphyses in children with resultant compromised height. Seizures have been reported rarely with the institution of levothyroxine therapy. Inadequate levothyroxine dosage will produce or fail to ameliorate the signs and symptoms of hypothyroidism. Hypersensitivity reactions to inactive ingredients have occurred in patients treated with thyroid hormone products. These include urticaria, pruritus, skin rash, flushing, angioedema, various Gl symptoms (abdominal pain, nausea, vomiting and diarrhea), fever, arthralgia, serum sickness and wheezing. Hypersensitivity to levothyroxine itself is not known to occur.

OVERDOSAGE


id: 5fdbfca5-67c5-358e-e053-2991aa0a4eb4
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5

The signs and symptoms of overdosage are those of hyperthyroidism (see
PRECAUTIONS and
ADVERSE REACTIONS ). In addition, confusion and disorientation may occur. Cerebral embolism, shock, coma, and death have been reported. Seizures have occurred in a child ingesting 18 mg of levothyroxine. Symptoms may not necessarily be evident or may not appear until several days after ingestion of levothyroxine sodium. Treatment of Overdosage Levothyroxine sodium should be reduced in dose or temporarily discontinued if signs or symptoms of overdosage occur. Acute Massive Overdosage – This may be a life-threatening emergency, therefore, symptomatic and supportive therapy should be instituted immediately. If not contraindicated (e.g., by seizures, coma, or loss of the gag reflex), the stomach should be emptied by emesis or gastric lavage to decrease gastrointestinal absorption. Activated charcoal or cholestyramine may also be used to decrease absorption. Central and peripheral increased sympathetic activity may be treated by administering β-receptor antagonists, e.g., propranolol, provided there are no medical contraindications to their use. Provide respiratory support as needed; control congestive heart failure and arrhythmia; control fever, hypoglycemia, and fluid loss as necessary. Large doses of antithyroid drugs (e.g., methimazole or propylthiouracil) followed in one to two hours by large doses of iodine may be given to inhibit synthesis and release of thyroid hormones. Glucocorticoids may be given to inhibit the conversion of T
4 to T
3. Plasmapheresis, charcoal hemoperfusion and exchange transfusion have been reserved for cases in which continued clinical deterioration occurs despite conventional therapy. Because T
4 is highly protein bound, very little drug will be removed by dialysis.

DOSAGE AND ADMINISTRATION


id: 5fdbfca5-67c6-358e-e053-2991aa0a4eb4
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7

General Principles: The goal of replacement therapy is to achieve and maintain a clinical and biochemical euthyroid state. The goal of suppressive therapy is to inhibit growth and/or function of abnormal thyroid tissue. The dose of Levothyroxine Sodium Tablets, USP that is adequate to achieve these goals depends on a variety of factors including the patient’s age, body weight, cardiovascular status, concomitant medical conditions, including pregnancy, concomitant medications, and the specific nature of the condition being treated (see
WARNINGS and
PRECAUTIONS ). Hence, the following recommendations serve only as dosing guidelines. Dosing must be individualized and adjustments made based on periodic assessment of the patient’s clinical response and laboratory parameters (see
PRECAUTIONS, Laboratory Tests ). Levothyroxine Sodium Tablets, USP should be taken in the morning on an empty stomach, at least one-half hour to one hour before any food is eaten. Levothyroxine Sodium Tablets, USP should be taken at least 4 hours apart from drugs that are known to interfere with its absorption (see
PRECAUTIONS, Drug Interactions ). Due to the long half-life of levothyroxine, the peak therapeutic effect at a given dose of levothyroxine sodium may not be attained for 4-6 weeks. Caution should be exercised when administering Levothyroxine Sodium Tablets, USP to patients with underlying cardiovascular disease, to the elderly, and to those with concomitant adrenal insufficiency (see
PRECAUTIONS ). Specific Patient Populations: Hypothyroidism in Adults and in Children in Whom Growth and Puberty are Complete (see
WARNINGS and
PRECAUTIONS, Laboratory Tests ). Therapy may begin at full replacement doses in otherwise healthy individuals less than 50 years old and in those older than 50 years who have been recently treated for hyperthyroidism or who have been hypothyroid for only a short time (such as a few months). The average full replacement dose of levothyroxine sodium is approximately 1.7 mcg/kg/day (e.g.,
100-125 mcg/day for a 70 kg adult). Older patients may require less than 1 mcg/kg/day. Levothyroxine sodium doses greater than 200 mcg/day are seldom required. An inadequate response to daily doses ≥ 300 mcg/day is rare and may indicate poor compliance, malabsorption, and/or drug interactions. For most patients older than 50 years or for patients under 50 years of age with underlying cardiac disease, an initial starting dose of
25-50 mcg/day of levothyroxine sodium is recommended, with gradual increments in dose at 6-8 week intervals, as needed. The recommended starting dose of levothyroxine sodium in elderly patients with cardiac disease is
12.5-25 mcg/day, with gradual dose increments at 4-6 week intervals. The levothyroxine sodium dose is generally adjusted in 12.5-25 mcg increments until the patient with primary hypothyroidism is clinically euthyroid and the serum TSH has normalized. In patients with severe hypothyroidism, the recommended initial levothyroxine sodium dose is
12.5-25 mcg/day with increases of 25 mcg/day every 2-4 weeks, accompanied by clinical and laboratory assessment, until the TSH level is normalized. In patients with secondary (pituitary) or tertiary (hypothalamic) hypothyroidism, the levothyroxine sodium dose should be titrated until the patient is clinically euthyroid and the serum free-T
4 level is restored to the upper half of the normal range. Pediatric Dosage – Congenital or Acquired Hypothyroidism (see
PRECAUTIONS, Laboratory Tests ) General Principles In general, levothyroxine therapy should be instituted at full replacement doses as soon as possible. Delays in diagnosis and institution of therapy may have deleterious effects on the child’s intellectual and physical growth and development. Undertreatment and overtreatment should be avoided (see
PRECAUTIONS, Pediatric Use ). Levothyroxine Sodium Tablets, USP may be administered to infants and children who cannot swallow intact tablets by crushing the tablet and suspending the freshly crushed tablet in a small amount (5-10 mL or 1-2 teaspoons) of water. This suspension can be administered by spoon or dropper.
DO NOT STORE THE SUSPENSION. Foods that decrease absorption of levothyroxine, such as soybean infant formula, should not be used for administering levothyroxine sodium tablets. (see
PRECAUTIONS, Drug-Food Interactions ). Newborns The recommended starting dose of levothyroxine sodium in newborn infants is
10-15 mcg/kg/day. A lower starting dose (e.g., 25 mcg/day) should be considered in infants at risk for cardiac failure, and the dose should be increased in 4-6 weeks as needed based on clinical and laboratory response to treatment. In infants with very low (< 5 mcg/dL) or undetectable serum T
4 concentrations, the recommended initial starting dose is
50 mcg/day of levothyroxine sodium. Infants and Children Levothyroxine therapy is usually initiated at full replacement doses, with the recommended dose per body weight decreasing with age (see
TABLE 3). However, in children with chronic or severe hypothyroidism, an initial dose of
25 mcg/day of levothyroxine sodium is recommended with increments of 25 mcg every 2-4 weeks until the desired effect is achieved. Hyperactivity in an older child can be minimized if the starting dose is one-fourth of the recommended full replacement dose, and the dose is then increased on a weekly basis by an amount equal to one-fourth the full-recommended replacement dose until the full recommended replacement dose is reached.

Table 3: Levothyroxine Sodium Dosing Guidelines for Pediatric Hypothyroidism
a. The dose should be adjusted based on clinical response and laboratory parameters (see 
PRECAUTlONS, Laboratory Tests and
Pediatric Use ).
AGE Daily Dose Per Kg Body Weight
a
0-3 months  10-15 mcg/kg/day
3-6 months  8-10 mcg/kg/day
6-12 months  6-8 mcg/kg/day
1-5 years  5-6 mcg/kg/day
6-12 years  4-5 mcg/kg/day
>12 years but growth and puberty incomplete 2-3 mcg/kg/day 
Growth and puberty complete  1.7 mcg/kg/day
Pregnancy- Pregnancy may increase levothyroxine requirements (see
PREGNANCY ). Subclinical Hypothyroidism- If this condition is treated, a lower levothyroxine sodium dose (e.g.,
1 mcg/kg/day) than that used for full replacement may be adequate to normalize the serum TSH level. Patients who are not treated should be monitored yearly for changes in clinical status and thyroid laboratory parameters. TSH Suppression in Well-differentiated Thyroid Cancer and Thyroid Nodules- The target level for TSH suppression in these conditions has not been established with controlled studies. In addition, the efficacy of TSH suppression for benign nodular disease is controversial. Therefore, the dose of Levothyroxine Sodium Tablets, USP used for TSH suppression should be individualized based on the specific disease and the patient being treated. In the treatment of well differentiated (papillary and follicular) thyroid cancer, levothyroxine is used as an adjunct to surgery and radioiodine therapy. Generally, TSH is suppressed to <0.1 mU/L, and this usually requires a levothyroxine sodium dose of
greater than 2 mcg/kg/day. However, in patients with high-risk tumors, the target level for TSH suppression may be <0.01 mU/L. In the treatment of benign nodules and nontoxic multinodular goiter, TSH is generally suppressed to a higher target (e.g., 0.1-0.5 mU/L for nodules and 0.5-1.0 mU/L for multinodular goiter) than that used for the treatment of thyroid cancer. Levothyroxine sodium is contraindicated if the serum TSH is already suppressed due to the risk of precipitating overt thyrotoxicosis (see
CONTRAINDICATIONS, WARNINGS and
PRECAUTIONS ). Myxedema Coma – Myxedema coma is a life-threatening emergency characterized by poor circulation and hypometabolism, and may result in unpredictable absorption of levothyroxine sodium from the gastrointestinal tract. Therefore, oral thyroid hormone drug products are not recommended to treat this condition. Thyroid hormone products formulated for intravenous administration should be administered.

HOW SUPPLIED


id: 5fdbfca5-67c7-358e-e053-2991aa0a4eb4
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5

Levothyroxine Sodium Tablets, USP are round, color coded, partial bisected tablets debossed with JSP and ID Number:

Strength (mcg) Color NDC# for bottles of 100 NDC# for bottles of 1000
 25  Peach  NDC 0527-1341-01  NDC 0527-1341 -10
 50  White  NDC 0527-1342-01  NDC 0527-1342 -10
 75  Purple  NDC 0527-1343-01  NDC 0527-1343 -10
 88  Olive  NDC 0527-1344-01  NDC 0527-1344 -10
 100  Yellow  NDC 0527-1345-01  NDC 0527-1345 -10
 112  Rose  NDC 0527-1346-01  NDC 0527-1346 -10
 125  Tan  NDC 0527-1347-01  NDC 0527-1347 -10
 137  Blue  NDC 0527-1638-01  NDC 0527-1638 -10
 150  Lt. Blue  NDC 0527-1349-01  NDC 0527-1349 -10
 175  Lilac  NDC 0527-1350-01  NDC 0527-1350 -10
 200  Pink  NDC 0527-1351-01  NDC 0527-1351 -10
 300  Green  NDC 0527-1352-01  NDC 0527-1352 -10
STORAGE CONDITIONS 20°C to 25°C (68°F to 77°F) with excursions between 15°C to 30°C (59°F to 86°F) Rx only Manufactured for:

Lannett Company, Inc.

Philadelphia, PA 19136 Manufactured by:

Jerome Stevens Pharmaceuticals, Inc.

Bohemia, NY 11716 Rev. 10/07 MG #18326