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LEVOTHYROXINE SODIUM  tablet
[REMEDYREPACK INC. ]


Category DEA Schedule Marketing Status
HUMAN PRESCRIPTION DRUG LABEL Abbreviated New Drug Application
Drug Label Sections

DESCRIPTION

DESCRIPTIONLevothyroxine sodium tablets, USP contains synthetic crystalline L-3,3222,5,5222-tetraiodothyronine sodium salt [levothyroxine (T4)sodium]. Synthetic T4 is identical to that produced in the human thyroid gland.Levothyroxine (T4) sodium has an empirical formula of C15H10I4N NaO4 x H2O, molecular weight of 798.86 g/mol (anhydrous), andstructural formula as shown:

INACTIVE INGREDIENT

Inactive IngredientsMagnesium Stearate, NF; Microcrystalline Cellulose, NF; Colloidal Silicone Dioxide, NF; Sodium Starch Glycolate, NF. Thefollowing are the color additives by tablet strength:Strength (mcg) Color Additive(s)
25 FD&C Yellow No. 6 Aluminum Lake
50 None
75 FD&C Blue No. 2
88 FD&C Blue No. 1 D&C Yellow No. 10 Aluminum Lake D&C Red No. 30 Aluminum Lake
100 D&C Yellow No. 10 D&C Red Lake Blend (D&C Red No. 27 D&C Red No. 30
112 D&C Red No. 27 D&C Red No. 30 FD&C Yellow No. 6 FD&C Red No. 40 FD&C Blue FD&C Blue No. 1
150 FD&C Blue No. 2
175 D&C Red No. 27 D&C Red No. 30 FD&C Blue No. 1
200 D&C Yellow No. 10 D&C Red No. 27
300D&C Yellow No. 10 FD&C Yellow No. 6 FD&C Blue No. 1 Meets USP Dissolution Test 2

CLINICAL PHARMACOLOGY

CLINICAL PHARMACOLOGY 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 (T4) and L-triiodothyronine (T3), by the thyroid gland. Circulating serum T3 and T4 levels exert a feedback effect on both TRH and TSH secretion. When serum T3 and T4 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. T3 and 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. 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 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. 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, and DOSAGE AND ADMINISTRATION).

PRECAUTIONS

PRECAUTIONS General Levothyroxine has a narrow therapeutic index. Regardless of the indication for use, careful dosage titration is necessary to avoid the consequences of over- or under-treatment. These consequences include, among others, effects on growth and development, cardiovascular function, bone metabolism, reproductive function, cognitive function, emotional state, gastrointestinal function, and on glucose and lipid metabolism. Many drugs interact with levothyroxine sodium necessitating adjustments in dosing to maintain therapeutic response (see Drug Interactions ). Effects on Bone Mineral Density In women, long-term levothyroxine sodium therapy has been associated with increased bone resorption, thereby decreasing bone mineral density, especially in post-menopausal women on greater than replacement doses or in women who are receiving suppressive doses of levothyroxine sodium. 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. Therefore, it is recommended that patients receiving levothyroxine sodium be given the minimum dose necessary to achieve the desired clinical and biochemical response. Patients with Underlying Cardiovascular Disease Exercise caution when administering levothyroxine to patients with cardiovascular disorders and to the elderly in whom there is an increased risk of occult cardiac disease. In these patients, levothyroxine therapy should be initiated at lower doses than those recommended in younger individuals or in patients without cardiac disease (see WARNINGS, PRECAUTIONS - Geriatric Use, and DOSAGE AND ADMINISTRATION). If cardiac symptoms develop or worsen, the levothyroxine dose should be reduced or withheld for one week and then cautiously restarted at a lower dose. Overtreatment with levothyroxine sodium may have adverse cardiovascular effects such as an increase in heart rate, cardiac wall thickness, and cardiac contractility and may precipitate angina or arrhythmias. Patients with coronary artery disease who are receiving levothyroxine therapy should be monitored closely during surgical procedures, since the possibility of precipitating cardiac arrhythmias may be greater in those treated with levothyroxine. Concomitant administration of levothyroxine and sympathomimetic agents to patients with coronary artery disease may precipitate coronary insufficiency. Patients with Nontoxic Diffuse Goiter or Nodular Thyroid Disease Exercise caution when administering levothyroxine to patients with nontoxic diffuse goiter or nodular thyroid disease in order to prevent precipitation of thyrotoxicosis (see WARNINGS ). If the serum TSH is already suppressed, levothyroxine sodium should not be administered (see CONTRAINDICATIONS ). Associated Endocrine Disorders Hypothalamic/pituitary hormone deficiencies In patients with secondary or tertiary hypothyroidism, additional hypothalamic/pituitary hormone deficiencies should be considered, and, if diagnosed, treated (see PRECAUTIONS - Autoimmune polyglandular syndrome for adrenal insufficiency). Autoimmune polyglandular syndrome Occasionally, chronic autoimmune thyroiditis may occur in association with other autoimmune disorders such as adrenal insufficiency, pernicious anemia, and insulin-dependent diabetes mellitus. Patients with concomitant adrenal insufficiency should be treated with replacement glucocorticoids prior to initiation of treatment with levothyroxine sodium. Failure to do so may precipitate an acute adrenal crisis when thyroid hormone therapy is initiated, due to increased metabolic clearance of glucocorticoids by thyroid hormone. Patients with diabetes mellitus may require upward adjustments of their antidiabetic therapeutic regimens when treated with levothyroxine (see PRECAUTIONS - Drug Interactions).

PHARMACOKINETICS

Pharmacokinetics Absorption Absorption of orally administered T4 from the gastrointestinal (GI) tract ranges from 40% to 80%. The majority of the levothyroxine dose is absorbed from the jejunum and upper ileum. The relative bioavailability of SYNTHROID tablets, compared to an equal nominal dose of oral levothyroxine sodium solution, is approximately 93%. T4 absorption is increased by fasting, and decreased in malabsorption syndromes and by certain foods such as soybean infant formula. Dietary fiber decreases bioavailability of T4. Absorption may also decrease with age. In addition, many drugs and foods affect T4 absorption (see PRECAUTIONS - Drug Interactions and Drug-Food Interactions ). Distribution Circulating thyroid hormones are greater than 99% bound to plasma proteins, including thyroxine-binding globulin (TBG), thyroxine-binding prealbumin (TBPA), and albumin (TBA), whose capacities and affinities vary for each hormone. The higher affinity of both TBG and TBPA for T4 partially explains the higher serum levels, slower metabolic clearance, and longer half-life of T4 compared to T3. Protein-bound thyroid hormones exist in reverse equilibrium with small amounts of free hormone. Only unbound hormone is metabolically active. Many drugs and physiologic conditions affect the binding of thyroid hormones to serum proteins (see PRECAUTIONS - Drug Interactions and Drug-Laboratory Test Interactions). Thyroid hormones do not readily cross the placental barrier (see PRECAUTIONS - Pregnancy). Metabolism T4 is slowly eliminated (see Table 1). The major pathway of thyroid hormone metabolism is through sequential deiodination. Approximately eighty-percent of circulating T3 is derived from peripheral T4 by monodeiodination. The liver is the major site of degradation for both T4 and T3, with T4 deiodination also occurring at a number of additional sites, including the kidney and other tissues. Approximately 80% of the daily dose of T4 is deiodinated to yield equal amounts of T3 and reverse T3 (rT3). T3 and rT3 are 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. Elimination Thyroid hormones are primarily eliminated by the kidneys. A portion of the conjugated hormone reaches the colon unchanged and is eliminated in the feces. Approximately 20% of T4 is eliminated in the stool. Urinary excretion of T4 decreases with age.

DRUG INTERACTIONS

Drug Interactions Many drugs 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 SYNTHROID. In addition, thyroid hormones and thyroid status have varied effects on the pharmacokinetics and actions of other drugs. A listing of drug-thyroidal axis interactions is contained in Table 2. The list of drug-thyroidal axis interactions in Table 2 may not be comprehensive due to the introduction of new drugs that interact with the thyroidal axis or the discovery of previously unknown interactions. The prescriber should be aware of this fact and should consult appropriate reference sources (e.g., package inserts of newly approved drugs, medical literature) for additional information if a drug-drug interaction with levothyroxine is suspected.

PREGNANCY

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 SYNTHROID 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 to either 0.5 or 1.0 mU/L) 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).

WARNINGS

Levothyroxine sodium should not be used in the treatment of male or female infertility unless this condition is associated with hypothyroidism. In patients with nontoxic diffuse goiter or nodular thyroid disease, particularly the elderly or those with underlying cardiovascular disease, levothyroxine sodium therapy is contraindicated if the serum TSH level is already suppressed due to the risk of precipitating overt thyrotoxicosis (see CONTRAINDICATIONS). If the serum TSH level is not suppressed, SYNTHROID should be used with caution in conjunction with careful monitoring of thyroid function for evidence of hyperthyroidism and clinical monitoring for potential associated adverse cardiovascular signs and symptoms of hyperthyroidism.

CONTRAINDICATIONS

CONTRAINDICATIONS Levothyroxine is contraindicated in patients with untreated subclinical (suppressed serum TSH level with normal T3 and T4 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). SYNTHROID is contraindicated in patients with hypersensitivity to any of the inactive ingredients in SYNTHROID tablets (See DESCRIPTION - Inactive Ingredients ).

GERIATRIC USE

Geriatric Use, andDOSAGE AND ADMINISTRATION).
If cardiac symptoms developor worsen, the levothyroxine dose should be reduced or withheld for one week and then cautiously restarted at a lower dose.
Overtreatment with levothyroxine sodium may have adverse cardiovascular effects such as an increase in heart rate, cardiac wallthickness, and cardiac contractility and may precipitate angina or arrhythmias. Patients with coronary artery disease who arereceiving levothyroxine therapy should be monitored closely during surgical procedures, since the possibility of precipitating cardiacarrhythmias may be greater in those treated with levothyroxine. Concomitant administration of levothyroxine and sympathomimeticagents to patients with coronary artery disease may precipitate coronary insufficiency.Patients with nontoxic diffuse goiter or nodular thyroid disease- Exercise caution when administering levothyroxine to patientswith nontoxic diffuse goiter or nodular thyroid disease in order to prevent precipitation of thyrotoxicosis (seeWARNINGS).
If theserum TSH is already suppressed, levothyroxine sodium should not be administered (seeCONTRAINDICATIONS).
Associated endocrine disordersHypothalamic/pituitary hormone deficiencies- In patients with secondary or tertiary hypothyroidism, additional hypothalamic/pituitary hormone deficiencies should be considered, and, if diagnosed, treated (seePRECAUTIONS, Autoimmune polyglandularsyndrome for adrenal insufficiency). Autoimmune polyglandular syndromeOccasionally, chronic autoimmune thyroiditis may occur in association with other autoimmune disorders such as adrenalinsufficiency, pernicious anemia, and insulin-dependent diabetes mellitus.
Patients with concomitant adrenal insufficiency should betreated with replacement glucocorticoids prior to initiation of treatment with levothyroxine sodium. Failure to do so may precipitatean acute adrenal crisis when thyroid hormone therapy is initiated, due to increased metabolic clearance of glucocorticoids by thyroid page 4 of 12 hormone. Patients with diabetes mellitus may require upward adjustments of their antidiabetic therapeutic regimens when treated withlevothyroxine (seePRECAUTIONS, Drug Interactions).Other associated medical conditionsInfants with congenital hypothyroidism appear to be at increased risk for other congenital anomalies, with cardiovascular anomalies(pulmonary stenosis, atrial septal defect, and ventricular septal defect) being the most common association.

INFORMATION FOR PATIENTS

Information for PatientsPatients should be informed of the following information to aid in the safe and effective use of Levothyroxine sodium tablets, USP:
1.Notify your physician if you are allergic to any foods or medicines, are pregnant or intend to become pregnant, are breast-feedingor are taking any other medications, including prescription and over-the-counter preparations.
2.Notify your physician of any other medical conditions you may have, particularly heart disease, diabetes, clotting disorders, andadrenal or pituitary gland problems. Your dose of medications used to control these other conditions may need to be adjustedwhile you are taking Levothyroxine sodium tablets, USP. If you have diabetes, monitor your blood and/or urinary glucose levelsas directed by your physician and immediately report any changes to your physician. If you are taking anticoagulants (bloodthinners), your clotting status should be checked frequently.
3.Use Levothyroxine sodium tablets, USP only as prescribed by your physician. Do not discontinue or change the amount you takeor how often you take it, unless directed to do so by your physician.
4.The levothyroxine in Levothyroxine sodium tablets, USP is intended to replace a hormone that is normally produced by yourthyroid gland. Generally, replacement therapy is to be taken for life, except in cases of transient hypothyroidism, which is usuallyassociated with an inflammation of the thyroid gland (thyroiditis).
5.Take Levothyroxine sodium tablets, USP as a single dose, preferably on an empty stomach, one-half to one hour before breakfast.Levothyroxine absorption is increased on an empty stomach.
6.Levothyroxine sodium tablets, USP may rapidly disintegrate. It is very important that you take the tablet with a full glass of water.
7.It may take several weeks before you notice an improvement in your symptoms.
8.Notify your physician if you experience any of the following symptoms: rapid or irregular heartbeat, chest pain, shortness ofbreath, 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 unusualmedical event.
9.Notify your physician if you become pregnant while taking Levothyroxine sodium tablets, USP. It is likely that your dose ofLevothyroxine sodium tablets, USP will need to be increased while you are pregnant.
10.Notify your physician or dentist that you are taking Levothyroxine sodium tablets, USP prior to any surgery.
11.Partial hair loss may occur rarely during the first few months of Levothyroxine sodium tablets, USP therapy, but this is usuallytemporary.
12.Levothyroxine sodium tablets, USP should not be used as a primary or adjunctive therapy in a weight control program.
13.Keep Levothyroxine sodium tablets, USP out of the reach of children. Store Levothyroxine sodium tablets, USP away from heat,moisture, and light.
14.Agents such as iron and calcium supplements and antacids can decrease the absorption of levothyroxine sodium tablets. Therefore,levothyroxine sodium tablets should not be administered within 4 hrs of these agents.

LABORATORY TESTS

Laboratory TestsGeneral The diagnosis of hypothyroidism is confirmed by measuring TSH levels using a sensitive assay (second generation assay sensitivity 2430.1 mIU/L or third generation assay sensitivity 243 0.01 mIU/L) and measurement of free-T4. The adequacy of therapy is determined by periodic assessment of appropriate laboratory tests and clinical evaluation. The choiceof laboratory tests depends on various factors including the etiology of the underlying thyroid disease, the presence of concomitantmedical conditions, including pregnancy, and the use of concomitant medications (seePRECAUTIONS, Drug Interactionsand Drug-Laboratory Test Interactions). Persistent clinical and laboratory evidence of hypothyroidism despite an apparent page 5 of 12 adequate replacement dose of Levothyroxine sodium tablets, USP may be evidence of inadequate absorption, poor compliance, druginteractions, or decreased T4 potency of the drug product.
Adults In adult patients with primary (thyroidal) hypothyroidism, serum TSH levels (using a sensitive assay) alone may be used to monitortherapy. The frequency of TSH monitoring during levothyroxine dose titration depends on the clinical situation but it is generallyrecommended at 6-8 week intervals until normalization.
For patients who have recently initiated levothyroxine therapy and whoseserum TSH has normalized or in patients who have had their dosage of levothyroxine changed, the serum TSH concentrationshould be measured after 8-12 weeks.
When the optimum replacement dose has been attained, clinical (physical examination)and biochemical monitoring may be performed every 6-12 months, depending on the clinical situation, and whenever there isa change in the patient222s status.
It is recommended that a physical examination and a serum TSH measurement be performed atleast annually in patients receiving Levothyroxine sodium tablets, USP (seeWARNINGS,PRECAUTIONS, andDOSAGE ANDADMINISTRATION). Pediatrics In patients with congenital hypothyroidism, the adequacy of replacement therapy should be assessed by measuring both serum TSH(using a sensitive assay) and total- or free-T4. During the first three years of life, the serum total- or free-T4 should be maintained atall times in the upper half of the normal range.
While the aim of therapy is to also normalize the serum TSH level, this is not alwayspossible in a small percentage of patients, particularly in the first few months of therapy.
TSH may not normalize due to a resetting ofthe pituitary-thyroid feedback threshold as a result of in utero hypothyroidism.
Failure of the serum T4 to increase into the upper halfof the normal range within 2 weeks of initiation of Levothyroxine sodium tablets, USP therapy and/or of the serum TSH to decreasebelow 20 mU/L within 4 weeks should alert the physician to the possibility that the child is not receiving adequate therapy. Carefulinquiry should then be made regarding compliance, dose of medication administered, and method of administration prior to raising thedose of Levothyroxine sodium tablets, USP.
The recommended frequency of monitoring of TSH and total- or free-T4 in children is as follows: at 2 and 4 weeks after the initiationof treatment; every 1-2 months during the first year of life; every 2-3 months between 1 and 3 years of age; and every 3 to 12 monthsthereafter until growth is completed.
More frequent intervals of monitoring may be necessary if poor compliance is suspected orabnormal values are obtained. It is recommended that TSH and T4 levels, and a physical examination, if indicated, be performed 2weeks after any change in Levothyroxine sodium tablets, USP dosage. Routine clinical examination, including assessment of mentaland physical growth and development, and bone maturation, should be performed at regular intervals (seePRECAUTIONS, PediatricUse and DOSAGE AND ADMINISTRATION).
Secondary (pituitary) and tertiary (hypothalamic) hypothyroidism Adequacy of therapy should be assessed by measuring serum free-T4 levels, which should be maintained in the upper half of thenormal range in these patients.Drug InteractionsMany drugs affect thyroid hormone pharmacokinetics and metabolism (e.g., absorption, synthesis, secretion, catabolism, proteinbinding, and target tissue response) and may alter the therapeutic response to Levothyroxine sodium tablets, USP.
In addition, thyroidhormones and thyroid status have varied effects on the pharmacokinetics and actions of other drugs.
A listing of drug-thyroidal axisinteractions is contained in Table 2.The list of drug-thyroidal axis interactions in Table 2 may not be comprehensive due to the introduction of new drugs that interactwith the thyroidal axis or the discovery of previously unknown interactions. The prescriber should be aware of this fact and shouldconsult appropriate reference sources (e.g., package inserts of newly approved drugs, medical literature) for additional information if adrug-drug interaction with levothyroxine is suspected. Table 2: Drug-Thyroidal Axis Interactions Drug or Drug Class Effect Drugs that may reduce TSH secretion226the reduction is not sustained; therefore, hypothyroidism does not occur Dopamine / Dopamine AgonistsGlucocorticoidsOctreotide Use of these agents may result in a transient reduction in TSH secretion whenadministered at the following doses: Dopamine ( 263 1 265g/kg/min); Glucocorticoids(hydrocortisone 263 100 mg/day or equivalent); Octreotide ( > 100 265g/day).
Drugs that alter thyroid hormone secretion Drugs that may decrease thyroid hormone secretion, which may result in hypothyroidism AminoglutethimideAmiodaroneIodide(including iodine-containing Radiographic contrast agents)LithiumMethimazolePropylthiouracil (PTU) Long-term lithium therapy can result in goiter in up to 50% of patients, and eithersubclinical or overt hypothyroidism, each in up to 20% of patients.
The fetus, neonate,elderly and euthyroid patients with underlying thyroid disease (e.g., Hashimoto222sthyroiditis or with Grave222s disease previously treated with radioiodine or surgery)are among those individuals who are particularly susceptible to iodine-inducedhypothyroidism. Oral cholecystographic agents and amiodarone are slowly excreted,producing more prolonged hypothyroidism than parenterally administered iodinated page 6 of 12 SulfonamidesTolbutamide contrast agents. Long-term aminoglutethimide therapy may minimally decrease T4 andT3 levels and increase TSH, although all values remain within normal limits in mostpatients.
Drugs that may increase thyroid hormone secretion, which may result in hyperthyroidism AmiodaroneIodide(including iodine-containing Radiographic contrast agents) Iodide and drugs that contain pharmacological amounts of iodide may causehyperthyroidism in euthyroid patients with Grave222s disease previously treated withantithyroid drugs or in euthyroid patients with thyroid autonomy (e.g., multinodulargoiter or hyperfunctioning thyroid adenoma).
Hyperthyroidism may develop overseveral weeks and may persist for several months after therapy discontinuation.Amiodarone may induce hyperthyroidism by causing thyroiditis. Drugs that may decrease T4 absorption, which may result in hypothyroidism Antacids- Aluminum & Magnesium Hydroxides- SimethiconeBile Acid Sequestrants- Cholestyramine- ColestipolCalcium CarbonateCation Exchange Resins- KayexalateFerrous SulfateOrlistatSucralfate Concurrent use may reduce the efficacy of levothyroxine by binding and delaying orpreventing absorption, potentially resulting in hypothyroidism.
Calcium carbonate mayform an insoluble chelate with levothyroxine, and ferrous sulfate likely forms a ferric-thyroxine complex.
Administer levothyroxine at least 4 hours apart from these agents.
Patients treated concomitantly with orlistat and levothyroxine should be monitored forchanges in thyroid function.
Drugs that may alter T4 and T3 serum transport - but FT4 concentrationremains normal; and, therefore, the patient remains euthyroid Drugs that may increase serum TBG concentration Drugs that may decreaseserum TBG concentration ClofibrateEstrogen-containing oral contraceptivesEstrogens (oral)Heroin / Methadone5-FluorouracilMitotaneTamoxifen Androgens / Anabolic SteroidsAsparaginaseGlucocorticoidsSlow-Release Nicotinic Acid Drugs that may cause protein-binding site displacement Furosemide (> 80 mg IV)HeparinHydantoinsNon Steroidal Anti-Inflammatory Drugs- Fenamates- PhenylbutazoneSalicylates (> 2 g/day)Administration of these agents with levothyroxine results in an initial transient increasein FT4.
Continued administration results in a decrease in serum T4, and normal FT4and TSH concentrations and, therefore, patients are clinically euthyroid.
Salicylatesinhibit binding of T4 and T3 to TBG and transthyretin. An initial increase in serum FT4is followed by return of FT4 to normal levels with sustained therapeutic serum salicylateconcentrations, although total-T4 levels may decrease by as much as 30%.
Drugs that may alter T4 and T3 metabolism Drugs that may increase hepatic metabolism, which may result in hypothyroidism CarbamazepineHydantoinsPhenobarbitalRifampin Stimulation of hepatic microsomal drug-metabolizing enzyme activity may causeincreased hepatic degradation of levothyroxine, resulting in increased levothyroxinerequirements. Phenytoin and carbamazepine reduce serum protein binding oflevothyroxine, and total- and free-T4 may be reduced by 20% to 40%, but most patientshave normal serum TSH levels and are clinically euthyroid. Drugs that may decrease T4 5222-deiodinase activity AmiodaroneBeta-adrenergic antagonists- (e.g., Propranolol > 160 mg/day)Glucocorticoids- (e.g., Dexamethasone 263 4 mg/day) Administration of these enzyme inhibitors decreases the peripheral conversion of T4 toT3, leading to decreased T3 levels. However, serum T4 levels are usually normal but mayoccasionally be slightly increased. In patients treated with large doses of propranolol (>160 mg/day), T3 and T4 levels change slightly, TSH levels remain normal, and patientsare clinically euthyroid. It should be noted that actions of particular beta-adrenergic page 7 of 12 Propylthiouracil (PTU) antagonists may be impaired when the hypothyroid patient is converted to the euthyroidstate. Short-term administration of large doses of glucocorticoids may decrease serumT3 concentrations by 30% with minimal change in serum T4 levels. However, long-termglucocorticoid therapy may result in slightly decreased T3 and T4 levels due to decreasedTBG production (see above). Miscellaneous Anticoagulants (oral)- Coumarin Derivatives- Indandione Derivatives Thyroid hormones appear to increase the catabolism of vitamin K-dependent clottingfactors, thereby increasing the anticoagulant activity of oral anticoagulants. Concomitantuse of these agents impairs the compensatory increases in clotting factor synthesis.Prothrombin time should be carefully monitored in patients taking levothyroxine andoral anticoagulants and the dose of anticoagulant therapy adjusted accordingly. Antidepressants- Tricyclics (e.g., Amitriptyline)- Tetracyclics(e.g., Maprotiline)- Selective Serotonin Reuptake Inhibitors (SSRIs; e.g., Sertraline)Concurrent use of tri/tetracyclic antidepressants and levothyroxine may increase thetherapeutic and toxic effects of both drugs, possibly due to increased receptor sensitivityto catecholamines. Toxic effects may include increased risk of cardiac arrhythmias andCNS stimulation; onset of action of tricyclics may be accelerated. Administration ofsertraline in patients stabilized on levothyroxine may result in increased levothyroxinerequirements.
Antidiabetic Agents- Biguanides- Meglitinides- Sulfonylureas- Thiazolidinediones- Insulin Addition of levothyroxine to antidiabetic or insulin therapy may result in increasedantidiabetic agent or insulin requirements. Careful monitoring of diabetic control isrecommended, especially when thyroid therapy is started, changed, or discontinued. Cardiac Glycosides Serum digitalis glycoside levels may be reduced in hyperthyroidism or when thehypothyroid patient is converted to the euthyroid state. Therapeutic effect of digitalisglycosides may be reduced. Cytokines- Interferon-a- Interleukin-2 Therapy with interferon-a has been associated with the development of antithyroidmicrosomal antibodies in 20% of patients and some have transient hypothyroidism,hyperthyroidism, or both. Patients who have antithyroid antibodies before treatment areat higher risk for thyroid dysfunction during treatment. Interleukin-2 has been associatedwith transient painless thyroiditis in 20% of patients. Interferon-b and -g have not beenreported to cause thyroid dysfunction. Growth Hormones- Somatrem- Somatropin Excessive use of thyroid hormones with growth hormones may accelerate epiphysealclosure. However, untreated hypothyroidism may interfere with growth response togrowth hormone. Ketamine Concurrent use may produce marked hypertension and tachycardia; cautiousadministration to patients receiving thyroid hormone therapy is recommended.
Methylxanthine Bronchodilators- (e.g., Theophylline) Decreased theophylline clearance may occur in hypothyroid patients; clearance returnsto normal when the euthyroid state is achieved.
Radiographic Agents Thyroid hormones may reduce the uptake of 123I, 131I, and 99mTc. Sympathomimetics Concurrent use may increase the effects of sympathomimetics or thyroidhormone. Thyroid hormones may increase the risk of coronary insufficiency whensympathomimetic agents are administered to patients with coronary artery disease. ChloralHydrateDiazepamEthionamideLovastatinMetoclopramide6-MercaptopurineNitroprussidePara-aminosalicylate sodiumPerphenazineResorcinol (excessive topical use)Thiazide Diuretics These agents have been associated with thyroid hormone and / or TSH level alterationsby various mechanisms. page 8 of 12 Oral anticoagulants - Levothyroxine increases the response to oral anticoagulant therapy.
Therefore, a decrease in the dose ofanticoagulant may be warranted with correction of the hypothyroid state or when the Levothyroxine sodium tablets, USP dose isincreased. Prothrombin time should be closely monitored to permit appropriate and timely dosage adjustments (see Table 2).Digitalis glycosides - The therapeutic effects of digitalis glycosides may be reduced by levothyroxine. Serum digitalis glycoside levelsmay be decreased when a hypothyroid patient becomes euthyroid, necessitating an increase in the dose of digitalis glycosides (seeTable 2).Drug-Food InteractionsConsumption of certain foods may affect levothyroxine absorption thereby necessitating adjustments in dosing. Soybean flour (infantformula), cotton seed meal, walnuts, and dietary fiber may bind and decrease the absorption of levothyroxine sodium from the GItract.Drug-Laboratory Test InteractionsChanges in TBG concentration must be considered when interpreting T4 and T3 values, which necessitates measurement andevaluation of unbound (free) hormone and/or determination of the free-T4 index (FT4I).
Pregnancy, infectious hepatitis, estrogens,estrogen-containing oral contraceptives, and acute intermittent porphyria increase TBG concentrations. Decreases in TBGconcentrations are observed in nephrosis, severe hypoproteinemia, severe liver disease, acromegaly, and after androgen orcorticosteroid therapy (see also Table 2). Familial hyper- or hypo-thyroxine binding globulinemias have been described, with theincidence of TBG deficiency approximating 1 in 9000.Carcinogenesis, Mutagenesis, and Impairment of FertilityAnimal studies have not been performed to evaluate the carcinogenic potential, mutagenic potential or effects on fertility oflevothyroxine. The synthetic T4 in Levothyroxine sodium tablets, USP is identical to that produced naturally by the human thyroidgland. Although there has been a reported association between prolonged thyroid hormone therapy and breast cancer, this has not beenconfirmed. Patients receiving Levothyroxine sodium tablets, USP for appropriate clinical indications should be titrated to the lowesteffective replacement dose. PregnancyCategory A 226 Studies in women taking levothyroxine sodium during pregnancy have not shown an increased risk of congenitalabnormalities. Therefore, the possibility of fetal harm appears remote. Levothyroxine sodium tablets, USP should not be discontinuedduring pregnancy and hypothyroidism diagnosed during pregnancy should be promptly treated.Hypothyroidism during pregnancy is associated with a higher rate of complications, including spontaneous abortion, pre-eclampsia,stillbirth and premature delivery.
Maternal hypothyroidism may have an adverse effect on fetal and childhood growth anddevelopment. During pregnancy, serum T4 levels may decrease and serum TSH levels increase to values outside the normal range.Since elevations in serum TSH may occur as early as 4 weeks gestation, pregnant women taking Levothyroxine sodium tablets, USPshould have their TSH measured during each trimester. An elevated serum TSH level should be corrected by an increase in the doseof Levothyroxine sodium tablets, USP. Since postpartum TSH levels are similar to preconception values, the Levothyroxine sodiumtablets, USP dosage should return to the pre-pregnancy dose immediately after delivery. A serum TSH level should be obtained 6-8weeks postpartum.Thyroid hormones cross the placental barrier to some extent as evidenced by levels in cord blood of athyreotic fetuses beingapproximately one-third maternal levels. Transfer of thyroid hormone from the mother to the fetus, however, may not be adequate toprevent in utero hypothyroidism.

NURSING MOTHERS

Nursing MothersAlthough thyroid hormones are excreted only minimally in human milk, caution should be exercised when Levothyroxine sodiumtablets, USP are administered to a nursing woman. However, adequate replacement doses of levothyroxine are generally needed tomaintain normal lactation.

PEDIATRIC USE

Pediatric UseGeneral The goal of treatment in pediatric patients with hypothyroidism is to achieve and maintain normal intellectual and physical growth anddevelopment.The initial dose of levothyroxine varies with age and body weight (seeDOSAGE AND ADMINISTRATION, Table 3). Dosingadjustments are based on an assessment of the individual patient222s clinical and laboratory parameters (seePRECAUTIONS,Laboratory Tests). In children in whom a diagnosis of permanent hypothyroidism has not been established, it is recommended that levothyroxineadministration be discontinued for a 30-day trial period, but only after the child is at least 3 years of age. Serum T4 and TSHlevels should then be obtained. If the T4 is low and the TSH high, the diagnosis of permanent hypothyroidism is established, andlevothyroxine therapy should be reinstituted. If the T4 and TSH levels are normal, euthyroidism may be assumed and, therefore,the hypothyroidism can be considered to have been transient.
In this instance, however, the physician should carefully monitor the page 9 of 12 child and repeat the thyroid function tests if any signs or symptoms of hypothyroidism develop. In this setting, the clinician shouldhave a high index of suspicion of relapse. If the results of the levothyroxine withdrawal test are inconclusive, careful follow-up andsubsequent testing will be necessary.Since some more severely affected children may become clinically hypothyroid when treatment is discontinued for 30 days, analternate approach is to reduce the replacement dose of levothyroxine by half during the 30-day trial period.
If, after 30 days, theserum TSH is elevated above 20 mU/L, the diagnosis of permanent hypothyroidism is confirmed, and full replacement therapy shouldbe resumed.
However, if the serum TSH has not risen to greater than 20 mU/L, levothyroxine treatment should be discontinued foranother 30-day trial period followed by repeat serum T4 and TSH testing.
The presence of concomitant medical conditions should be considered in certain clinical circumstances and, if present, appropriatelytreated (seePRECAUTIONS). Congenital Hypothyroidism ( seePRECAUTIONS, Laboratory Tests and DOSAGE and ADMINISTRATION)Rapid restoration of normal serum T4 concentrations is essential for preventing the adverse effects of congenital hypothyroidism onintellectual development as well as on overall physical growth and maturation.
Therefore, Levothyroxine sodium tablets, USP therapyshould be initiated immediately upon diagnosis and is generally continued for life.
During the first 2 weeks of Levothyroxine sodium tablets, USP therapy, infants should be closely monitored for cardiac overload,arrhythmias, and aspiration from avid suckling.The patient should be monitored closely to avoid undertreatment or overtreatment. Undertreatment may have deleterious effects onintellectual development and linear growth. Overtreatment has been associated with craniosynostosis in infants, and may adverselyaffect the tempo of brain maturation and accelerate the bone age with resultant premature closure of the epiphyses and compromisedadult stature.
Acquired Hypothyroidism in Pediatric Patients The patient should be monitored closely to avoid undertreatment and overtreatment. Undertreatment may result in poor schoolperformance due to impaired concentration and slowed mentation and in reduced adult height.
Overtreatment may accelerate the boneage 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.Geriatric UseBecause of the increased prevalence of cardiovascular disease among the elderly, levothyroxine therapy should not be initiated at thefull replacement dose (seeWARNINGS,PRECAUTIONS, andDOSAGE AND ADMINISTRATION).

ADVERSE REACTIONS

ADVERSE REACTIONS 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 elevations 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 adult 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 GI symptoms (abdominal pain, nausea, vomiting and diarrhea), fever, arthralgia, serum sickness and wheezing. Hypersensitivity to levothyroxine itself is not known to occur. Overdosage 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.

OVERDOSAGE

overdosage(seePRECAUTIONS andOVERDOSAGE).
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, myocardialinfarction, cardiac arrest;Respiratory: dyspnea;Gastrointestinal: diarrhea, vomiting, abdominal cramps and elevations in liver function tests;Dermatologic: hair loss, flushing;Endocrine: decreased bone mineral density;Reproductive: menstrual irregularities, impaired fertility.Pseudotumor cerebri and slipped capital femoral epiphyses 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 compromisedadult 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 includeurticaria, pruritus, skin rash, flushing, angioedema, various GI symptoms (abdominal pain, nausea, vomiting and diarrhea), fever,arthralgia, serum sickness and wheezing. Hypersensitivity to levothyroxine itself is not known to occur.
OVERDOSAGEThe signs and symptoms of overdosage are those of hyperthyroidism (seePRECAUTIONS andADVERSE REACTIONS).
Inaddition, confusion and disorientation may occur. Cerebral embolism, shock, coma, and death have been reported. Seizures haveoccurred in a child ingesting 18 mg of levothyroxine. Symptoms may not necessarily be evident or may not appear until several daysafter ingestion of levothyroxine sodium.Treatment of OverdosageLevothyroxine sodium should be reduced in dose or temporarily discontinued if signs or symptoms of overdosage occur. page 10 of 12 Acute Massive Overdosage 226 This may be a life-threatening emergency, therefore, symptomatic and supportive therapy should beinstituted immediately.
If not contraindicated (e.g., by seizures, coma, or loss of the gag reflex), the stomach should be emptied byemesis or gastric lavage to decrease gastrointestinal absorption. Activated charcoal or cholestyramine may also be used to decreaseabsorption. Central and peripheral increased sympathetic activity may be treated by administering b-receptor antagonists, e.g.,propranolol, provided there are no medical contraindications to their use. Provide respiratory support as needed; control congestiveheart 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 releaseof thyroid hormones. Glucocorticoids may be given to inhibit the conversion of T4 to T3. Plasmapheresis, charcoal hemoperfusion,and exchange transfusion have been reserved for cases in which continued clinical deterioration occurs despite conventional therapy.Because T4 is highly protein bound, very little drug will be removed by dialysis. DOSAGE AND ADMINISTRATIONGeneral PrinciplesThe goal of replacement therapy is to achieve and maintain a clinical and biochemical euthyroid state.
The goal of suppressivetherapy is to inhibit growth and/or function of abnormal thyroid tissue. The dose of Levothyroxine sodium tablets, USP that isadequate to achieve these goals depends on a variety of factors including the patient222s age, body weight, cardiovascular status,concomitant medical conditions, including pregnancy, concomitant medications, and the specific nature of the condition being treated(seeWARNINGS andPRECAUTIONS). Hence, the following recommendations serve only as dosing guidelines. Dosing mustbe individualized and adjustments made based on periodic assessment of the patient222s clinical response and laboratory parameters(seePRECAUTIONS, Laboratory Tests). Levothyroxine sodium tablets, USP are administered as a single daily dose, preferably one-half to one-hour before breakfast.
Levothyroxine sodium tablets, USP should be taken at least 4 hours apart from drugs that are known to interfere with its absorption(seePRECAUTIONS, Drug Interactions). Levothyroxine sodium tablets, USP should be taken with a full glass of water,(seeInformation for Patients). Due to the long half-life of levothyroxine, the peak therapeutic effect at a given dose of Levothyroxine sodium tablets, USP may notbe attained for 4-6 weeks.Caution should be exercised when administering Levothyroxine sodium tablets, USP to patients with underlying cardiovasculardisease, to the elderly, and to those with concomitant adrenal insufficiency (seePRECAUTIONS).
Specific Patient PopulationsHypothyroidism in Adults and in Children in Whom Growth and Puberty are Complete (see WARNINGS andPRECAUTIONS,Laboratory Tests)Therapy may begin at full replacement doses in otherwise healthy individuals who are at low risk of coronary artery disease. Theaverage 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. Aninadequate response to daily doses 263 300 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 doseof 25-50 mcg/day of levothyroxine sodium is recommended, with gradual increments in dose at 6-8 week intervals, as needed. Therecommended starting dose of levothyroxine sodium in elderly patients with cardiac disease is 12.5-25 mcg/day, with gradual doseincrements at 4-6 week intervals. The levothyroxine sodium dose is generally adjusted in 12.5-25 mcg increments until the patientwith 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 25mcg/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 titrateduntil the patient is clinically euthyroid and the serum free-T4 level is restored to the upper half of the normal range. Pediatric Dosage 226 Congenital or Acquired Hypothyroidism (see PRECAUTIONS, Laboratory Tests)General PrinciplesIn general, levothyroxine therapy should be instituted at full replacement doses as soon as possible. Delays in diagnosis and institutionof therapy may have deleterious effects on the child222s intellectual and physical growth and development.Undertreatment and overtreatment should be avoided (seePRECAUTIONS, Pediatric Use).
Levothyroxine sodium tablets, USP may be administered to infants and children who cannot swallow intact tablets by crushing thetablet and suspending the freshly crushed tablet in a small amount (5-10 mL or 1-2 teaspoons) of water. This suspension can beadministered by spoon or dropper. DO NOT STORE THE SUSPENSION.
Foods that decrease absorption of levothyroxine, suchas soybean infant formula, should not be used for administering levothyroxine sodium tablets (seePRECAUTIONS , Drug-FoodInteractions)
NewbornsThe recommended starting dose of levothyroxine sodium in newborn infants is 10-15 mcg/kg/day. A lower starting dose (e.g., 25mcg/day) should be considered in infants at risk for cardiac failure, and the dose should be increased in 4-6 weeks as needed basedon clinical and laboratory response to treatment. In infants with very low (< 5 mcg/dL) or undetectable serum T4 concentrations, therecommended initial starting dose is 50 mcg/day of levothyroxine sodium. page 11 of 12 Infants and ChildrenLevothyroxine 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 isrecommended 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, andthe dose is then increased on a weekly basis by an amount equal to one-fourth the full-recommended replacement dose until the fullrecommended replacement dose is reached.
Table 3: Levothyroxine Sodium Dosing Guidelines for Pediatric Hypothyroidism AGE Daily Dose Per Kg Body Weighta 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 a The dose should be adjusted based on clinical response and laboratory parameters (see PRECAUTIONS, Laboratory Tests andPediatric Use). Pregnancy- Pregnancy may increase levothyroxine requirements (seePregnancy).
Subclinical Hypothyroidism- If this condition is treated, a lower levothyroxine sodium dose (e.g., 1 mcg/kg/day) than that used forfull replacement may be adequate to normalize the serum TSH level.
Patients who are not treated should be monitored yearly forchanges in clinical status and thyroid laboratory parameters.TSH Suppression in Well-differentiated Thyroid Cancer and Thyroid Nodules 226The target level for TSH suppression in theseconditions has not been established with controlled studies. In addition, the efficacy of TSH suppression for benign nodular disease iscontroversial. Therefore, the dose of Levothyroxine sodium tablets, USP used for TSH suppression should be individualized based onthe 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 andradioiodine therapy.
Generally, TSH is suppressed to <0.1 mU/L, and this usually requires a levothyroxine sodium dose of greaterthan 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 toeither 0.5 or 1.0 mU/L) than that used for the treatment of thyroid cancer. Levothyroxine sodium is contraindicated if the serumTSH is already suppressed due to the risk of precipitating overt thyrotoxicosis (seeCONTRAINDICATIONS, WARNINGSandPRECAUTIONS).
Myxedema Coma 226 Myxedema coma is a life-threatening emergency characterized by poor circulation and hypometabolism, andmay result in unpredictable absorption of levothyroxine sodium from the gastrointestinal tract.
Therefore, oral thyroid hormone drugproducts are not recommended to treat this condition. Intravenous levothyroxine sodium should be administered.

HOW SUPPLIED

HOW SUPPLIEDLevothyroxine sodium tablets, USP are supplied as scored, color coded potency marked tablets as follows:25 mcg, capsule shape tablets, orange color, on one side debossed with "25"; on the other side bisected and debossed with "GG" to theleft of the bisect and "331" to the right:
NDC 0781-5180-01 Bottle of 100222
sNDC 0781-5180-10 Bottle of 1000222s50 mcg, capsule shape tablets, white color, on one side debossed with "50"; on the other side bisected and debossed with "GG" to theleft of the bisect and "332" to the right:NDC 0781-5181-01 Bottle of 100222sNDC 0781-5181-10 Bottle of 1000222s75 mcg, capsule shape tablets, dark blue color, on one side debossed with "75"; on the other side bisected and debossed with "GG" tothe left of the bisect and "333" to the right:NDC 0781-5182-01 Bottle of 100222s
NDC 0781-5182-10 Bottle of 1000222s88 mcg, capsule shape tablets, olive green color, on one side debossed with "88"; on the other side bisected and debossed with "GG"to the left of the bisect and "334" to the right:
NDC 0781-5183-01 Bottle of 100222sNDC 0781-5183-10 Bottle of 1000222s page 12 of 12 100 mcg, capsule shape tablets, yellow color, on one side debossed with "100"; on the other side bisected and debossed with "GG" tothe left of the bisect and "335" to the right:
NDC 0781-5184-01 Bottle of 100222s
NDC 0781-5184-10 Bottle of 1000222s112 mcg, capsule shape tablets, rose color, on one side debossed with "112"; on the other side bisected and debossed with "GG" to theleft of the bisect and "336" to the right:NDC 0781-5185-01 Bottle of 100222sNDC 0781-5185-10 Bottle of 1000222s125 mcg, capsule shape tablets, brown color, on one side debossed with "125"; on the other side bisected and debossed with "GG" tothe left of the bisect and "337" to the right:NDC 0781-5186-01 Bottle of 100222s
NDC 0781-5186-10 Bottle of 1000222s137 mcg, capsule shape tablets, turquoise color, on one side debossed with "137"; on the other side bisected and debossed with "GG"to the left of the bisect and "330" to the right
:NDC 0781-5191-01 Bottle of 100222s
NDC 0781-5191-10 Bottle of 1000222s150 mcg, capsule shape tablets, blue color, on one side debossed with "150"; on the other side bisected and debossed with "GG" to theleft of the bisect and "338" to the right:
NDC 0781-5187-01 Bottle of 100222sNDC 0781-5187-10 Bottle of 1000222s175 mcg, capsule shape tablets, lilac color, on one side debossed with "175"; on the other side bisected and debossed with "GG" to theleft of the bisect and "339" to the right:NDC 0781-5188-01 Bottle of 100222sNDC 0781-5188-10 Bottle of 1000222s200 mcg, capsule shape tablets, pink color, on one side debossed with "200"; on the other side bisected and debossed with "GG" to theleft of the bisect and "340" to the right:
NDC 0781-5189-01 Bottle of 100222sNDC 0781-5189-10 Bottle of 1000222s300 mcg, capsule shape tablets, green color, on one side debossed with "300"; on the other side bisected and debossed with "GG" tothe left of the bisect and "341" to the right:
NDC 0781-5190-01 Bottle of 100222
sNDC 0781-5190-10 Bottle of 1000222sSTORAGE CONDITIONSStore at controlled room temperature 20272 to 25272C (68272 to 77272F) with excursions permitted between 15272 and 30272C (59272 and 86272F).Dispense in a tight, light-resistant container with a child-resistant closure.Manufactured by:MOVA PHARMACEUTICAL CORPORATIONCaguas, Puerto Rico 00725, USAFor:ALARA Pharmaceutical CorporationCaguas, Puerto Rico 00725, USADistributed by:Sandoz Inc.Broomfield, CO 80020Revised: 10/076310403

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL

DRUG: Levothyroxine Sodium Sodium
GENERIC: Levothyroxine Sodium
DOSAGE: TABLET
ADMINSTRATION: ORAL
NDC: 49349-007-02
STRENGTH:112 mcg
COLOR: pink
SHAPE: CAPSULE
SCORE: No score
SIZE: 9 mm
IMPRINT: 30
QTY: 30

IMAGE OF PRODUCT LABEL
IMAGE OF CARTON
LEVOTHYROXINE SODIUM  
levothyroxine sodium tablet
Product Information
Product TypeHUMAN PRESCRIPTION DRUG LABELItem Code (Source)NDC:49349-007(NDC:0781-5185)
Route of AdministrationORALDEA Schedule    
Active Ingredient/Active Moiety
Ingredient NameBasis of StrengthStrength
LEVOTHYROXINE SODIUM (LEVOTHYROXINE) LEVOTHYROXINE SODIUM0.112 mg
Inactive Ingredients
Ingredient NameStrength
MAGNESIUM STEARATE 
CELLULOSE, MICROCRYSTALLINE 
SODIUM STARCH GLYCOLATE TYPE A POTATO 
Product Characteristics
ColorpinkScoreno score
ShapeCAPSULE (TABLET) Size9mm
FlavorImprint Code 112;GG;336
Contains    
Packaging
#Item CodePackage DescriptionMarketing Start DateMarketing End Date
1NDC:49349-007-0230 in 1 BLISTER PACK
Marketing Information
Marketing CategoryApplication Number or Monograph CitationMarketing Start DateMarketing End Date
ANDAANDA07675208/04/2010
Labeler - REMEDYREPACK INC. (829572556)

Revised: 8/2010
 
REMEDYREPACK INC.

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