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| Product NDC Code | 55466-108 | ||||||
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| Drug Name | Levo-t |
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| Type | Brand | ||||||
| Pharm Class | Thyroxine [CS], l-Thyroxine [EPC] |
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| Active Ingredients |
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| Route | ORAL | ||||||
| Dosage Form | TABLET | ||||||
| RxCUI drug identifier | 892246, 892251, 892255, 966154, 966161, 966167, 966178, 966188, 966197, 966208, 966214, 966220, 966221, 966222, 966224, 966225, 966248, 966249, 966253, 966270, 966397, 966399, 966401, 966410 |
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| Application Number | NDA021342 | ||||||
| Labeler Name | Neolpharma, Inc. | ||||||
| Packages |
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Overdosage of LEVO-T
Information about signs, symptoms, and laboratory findings of acute ovedosage and the general principles of overdose treatment.10 OVERDOSAGE The signs and symptoms of overdosage are those of hyperthyroidism [see Warnings and Precautions (5) and Adverse Reactions (6)] . In addition, confusion and disorientation may occur. Cerebral embolism, shock, coma, and death have been reported. Seizures occurred in a 3-year- old child ingesting 3.6 mg of levothyroxine. Symptoms may not necessarily be evident or may not appear until several days after ingestion of levothyroxine sodium. Reduce the LEVO-T dose or discontinue temporarily if signs or symptoms of overdosage occur. Initiate appropriate supportive treatment as dictated by the patient’s medical status. For current information on the management of poisoning or overdosage, contact the National Poison Control Center at 1-800-222-1222 or www.poison.org.
Adverse reactions
Information about undesirable effects, reasonably associated with use of the drug, that may occur as part of the pharmacological action of the drug or may be unpredictable in its occurrence. Adverse reactions include those that occur with the drug, and if applicable, with drugs in the same pharmacologically active and chemically related class. There is considerable variation in the listing of adverse reactions. They may be categorized by organ system, by severity of reaction, by frequency, by toxicological mechanism, or by a combination of these.6 ADVERSE REACTIONS Adverse reactions associated with LEVO-T therapy are primarily those of hyperthyroidism due to therapeutic overdosage [see Warnings and Precautions (5), 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, muscle spasm 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, rash Endocrine: decreased bone mineral density Reproductive: menstrual irregularities, impaired fertility Seizures have been reported rarely with the institution of levothyroxine therapy. Adverse reactions associated with LEVO-T therapy are primarily those of hyperthyroidism due to therapeutic overdosage: arrhythmias, myocardial infarction, dyspnea, muscle spasm, 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 Neolpharma, Inc. at 1-844-200-4163 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. Adverse Reactions in Pediatric Patients Pseudotumor cerebri and slipped capital femoral epiphysis have been reported in pediatric patients receiving levothyroxine therapy. Overtreatment may result in craniosynostosis in infants who have not undergone complete closure of the fontanelles, and in premature closure of the epiphyses in pediatric patients still experiencing growth 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. Hypersensitivity to levothyroxine itself is not known to occur.
LEVO-T Drug Interactions
Information about and practical guidance on preventing clinically significant drug/drug and drug/food interactions that may occur in people taking the drug.7 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 LEVO-T. ( 7 ) 7.1 Drugs Known to Affect Thyroid Hormone Pharmacokinetics Many drugs can exert effects on thyroid hormone pharmacokinetics and metabolism (e.g., absorption, synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to LEVO-T (Tables 5 to 8). Table 5. Drugs That May Decrease T4 Absorption (Hypothyroidism) Potential impact: Concurrent use may reduce the efficacy of LEVO-T by binding and delaying or preventing absorption, potentially resulting in hypothyroidism. Drug or Drug Class Effect Phosphate Binders (e.g., calcium carbonate, ferrous sulfate, sevelamer, lanthanum) Phosphate binders may bind to levothyroxine. Administer LEVO-T at least 4 hours apart from these agents. Orlistat Monitor patients treated concomitantly with orlistat and LEVO-T for changes in thyroid function. Bile Acid Sequestrants (e.g., colesevelam, cholestyramine, colestipol) Ion Exchange Resins (e.g., Kayexalate) Bile acid sequestrants and ion exchange resins are known to decrease levothyroxine absorption. Administer LEVO-T at least 4 hours prior to these drugs or monitor TSH levels. Proton Pump Inhibitors Sucralfate Antacids (e.g., aluminum & magnesium hydroxides, simethicone) Gastric acidity is an essential requirement for adequate absorption of levothyroxine. Sucralfate, antacids and proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce levothyroxine absorption. Monitor patients appropriately. Table 6. Drugs That May Alter T4 and 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. Potential impact (below): Administration of these agents with LEVO-T results in an initial transient increase in FT4. Continued administration results in a decrease in serum T4 and normal FT4 and TSH concentrations. 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 increase 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 levothyroxine, and total and free T4 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 7. Drugs That May Alter Hepatic Metabolism of T4 (Hypothyroidism) Potential impact: Stimulation of hepatic microsomal drug-metabolizing enzyme activity may cause increased hepatic degradation of levothyroxine, resulting in increased LEVO-T 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 levothyroxine. Table 8. 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 LEVO-T 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 thyroid therapy is started, changed, or discontinued [see Warnings and Precautions (5.5)] . 7.3 Oral Anticoagulants LEVO-T 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 LEVO-T dose is increased. Closely monitor coagulation tests to permit appropriate and timely dosage adjustments. 7.4 Digitalis Glycosides LEVO-T may reduce the therapeutic effects of digitalis glycosides. Serum digitalis glycoside levels may decrease 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 LEVO-T 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. LEVO-T may accelerate the onset of action of tricyclics. Administration of sertraline in patients stabilized on LEVO-T may result in increased LEVO-T requirements. 7.6 Ketamine Concurrent use of ketamine and LEVO-T may produce marked hypertension and tachycardia. Closely monitor blood pressure and heart rate in these patients. 7.7 Sympathomimetics Concurrent use of sympathomimetics and LEVO-T 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-Food Interactions Consumption of certain foods may affect LEVO-T absorption thereby necessitating adjustments in dosing [see Dosage and Administration (2.1)] . Soybean flour, cottonseed meal, walnuts, and dietary fiber may bind and decrease the absorption of LEVO-T from the gastrointestinal tract. Grapefruit juice may delay the absorption of levothyroxine and reduce its bioavailability. 7.10 Drug-Laboratory Test Interactions Thyroxine-binding Globulin (TBG) Consider changes in TBG concentration when interpreting T4 and T3 values. Measure and evaluate unbound (free) hormone and/or determine the free-T4 index (FT4I) in this circumstance. Pregnancy, infectious hepatitis, estrogens, estrogen-containing oral contraceptives, and acute intermittent porphyria increase TBG concentration. 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. Biotin Biotin supplementation is known to interfere with thyroid hormone immunoassays that are based on a biotin and streptavidin interaction, which may result in erroneous thyroid hormone test results. Stop biotin and biotin-containing supplements for at least 2 days prior to thyroid testing.
| Potential impact: Concurrent use may reduce the efficacy of LEVO-T by binding and delaying or preventing absorption, potentially resulting in hypothyroidism. | |
| Phosphate binders may bind to levothyroxine. Administer LEVO-T at least 4 hours apart from these agents. | |
| Orlistat | Monitor patients treated concomitantly with orlistat and LEVO-T for changes in thyroid function. |
| Bile Acid Sequestrants | Bile acid sequestrants and ion exchange resins are known to decrease levothyroxine absorption. Administer LEVO-T at least 4 hours prior to these drugs or monitor TSH levels. |
| Gastric acidity is an essential requirement for adequate absorption of levothyroxine. Sucralfate, antacids and proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce levothyroxine absorption. Monitor patients appropriately. | |
| 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. |
| Potential impact (below): Administration of these agents with LEVO-T results in an initial transient increase in FT4. Continued administration results in a decrease in serum T4 and normal FT4 and TSH concentrations. | |
| 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 increase 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 levothyroxine, and total and free T4 may be reduced by 20% to 40%, but most patients have normal serum TSH levels and are clinically euthyroid. Closely monitor thyroid hormone parameters. |
| Potential impact: Stimulation of hepatic microsomal drug-metabolizing enzyme activity may cause increased hepatic degradation of levothyroxine, resulting in increased LEVO-T requirements. | |
| 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 levothyroxine. |
| 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. | |
| 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. |
Clinical pharmacology
Information about the clinical pharmacology and actions of the drug in humans.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 Oral levothyroxine sodium is a synthetic T4 hormone that exerts the same physiologic effect as endogenous T4, thereby maintaining normal T4 levels when a deficiency is present. 12.3 Pharmacokinetics Absorption Absorption of orally administered T4 from the gastrointestinal tract ranges from 40% to 80%. The majority of the LEVO-T dose is absorbed from the jejunum and upper ileum. The relative bioavailability of LEVO-T tablets, compared to an equal nominal dose of oral levothyroxine sodium solution, is approximately 99%. T4 absorption is increased by fasting, and decreased in malabsorption syndromes and by certain foods such as soybeans. Dietary fiber decreases bioavailability of T4. Absorption may also decrease with age. In addition, many drugs and foods affect T4 absorption [see Drug Interactions (7)] . 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 Drug Interactions (7)] . Thyroid hormones do not readily cross the placental barrier [see Use in Specific Populations (8.1)] . Elimination Metabolism T4 is slowly eliminated (Table 10). 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, 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. 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. Approximately 20% of T4 is eliminated in the stool. Urinary excretion of T4 decreases with age. Table 10. Pharmacokinetic Parameters of Thyroid Hormones in Euthyroid Patients Hormone Ratio in Thyroglobulin Biologic Potency t 1/2 (days) Protein Binding (%) Levothyroxine (T4) 10 - 20 1 6-7 ** 99.96 Liothyronine (T3) 1 4 ≤ 2 99.5 *Includes TBG, TBPA, and TBA **3 to 4 days in hyperthyroidism, 9 to 10 days in hypothyroidism
| Hormone | Ratio in Thyroglobulin | Biologic Potency | t 1/2 (days) | Protein Binding (%) |
|---|---|---|---|---|
| Levothyroxine (T4) | 10 - 20 | 1 | 6-7 ** | 99.96 |
| Liothyronine (T3) | 1 | 4 | ≤ 2 | 99.5 |
| *Includes TBG, TBPA, and TBA **3 to 4 days in hyperthyroidism, 9 to 10 days in hypothyroidism | ||||
Mechanism of action
Information about the established mechanism(s) of the drugÕs action in humans at various levels (for example receptor, membrane, tissue, organ, whole body). If the mechanism of action is not known, this field contains a statement about the lack of information.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.
Pharmacodynamics
Information about any biochemical or physiologic pharmacologic effects of the drug or active metabolites related to the drugÕs clinical effect in preventing, diagnosing, mitigating, curing, or treating disease, or those related to adverse effects or toxicity.12.2 Pharmacodynamics Oral levothyroxine sodium is a synthetic T4 hormone that exerts the same physiologic effect as endogenous T4, thereby maintaining normal T4 levels when a deficiency is present.
Pharmacokinetics
Information about the clinically significant pharmacokinetics of a drug or active metabolites, for instance pertinent absorption, distribution, metabolism, and excretion parameters.12.3 Pharmacokinetics Absorption Absorption of orally administered T4 from the gastrointestinal tract ranges from 40% to 80%. The majority of the LEVO-T dose is absorbed from the jejunum and upper ileum. The relative bioavailability of LEVO-T tablets, compared to an equal nominal dose of oral levothyroxine sodium solution, is approximately 99%. T4 absorption is increased by fasting, and decreased in malabsorption syndromes and by certain foods such as soybeans. Dietary fiber decreases bioavailability of T4. Absorption may also decrease with age. In addition, many drugs and foods affect T4 absorption [see Drug Interactions (7)] . 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 Drug Interactions (7)] . Thyroid hormones do not readily cross the placental barrier [see Use in Specific Populations (8.1)] . Elimination Metabolism T4 is slowly eliminated (Table 10). 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, 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. 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. Approximately 20% of T4 is eliminated in the stool. Urinary excretion of T4 decreases with age. Table 10. Pharmacokinetic Parameters of Thyroid Hormones in Euthyroid Patients Hormone Ratio in Thyroglobulin Biologic Potency t 1/2 (days) Protein Binding (%) Levothyroxine (T4) 10 - 20 1 6-7 ** 99.96 Liothyronine (T3) 1 4 ≤ 2 99.5 *Includes TBG, TBPA, and TBA **3 to 4 days in hyperthyroidism, 9 to 10 days in hypothyroidism
| Hormone | Ratio in Thyroglobulin | Biologic Potency | t 1/2 (days) | Protein Binding (%) |
|---|---|---|---|---|
| Levothyroxine (T4) | 10 - 20 | 1 | 6-7 ** | 99.96 |
| Liothyronine (T3) | 1 | 4 | ≤ 2 | 99.5 |
| *Includes TBG, TBPA, and TBA **3 to 4 days in hyperthyroidism, 9 to 10 days in hypothyroidism | ||||
Contraindications
Information about situations in which the drug product is contraindicated or should not be used because the risk of use clearly outweighs any possible benefit, including the type and nature of reactions that have been reported.4 CONTRAINDICATIONS LEVO-T is contraindicated in patients with uncorrected adrenal insufficiency [see Warnings and Precautions (5.4)] . Uncorrected adrenal insufficiency. (4)
Description
General information about the drug product, including the proprietary and established name of the drug, the type of dosage form and route of administration to which the label applies, qualitative and quantitative ingredient information, the pharmacologic or therapeutic class of the drug, and the chemical name and structural formula of the drug.11 DESCRIPTION LEVO-T (levothyroxine sodium tablets, USP) contain synthetic crystalline L-3,3',5,5'-tetraiodothyronine sodium salt [levothyroxine (T4) sodium]. Synthetic T4 is chemically identical to that produced in the human thyroid gland. Levothyroxine (T4) sodium has an empirical formula of C 15 H 10 I 4 NNaO 4 ∙x H 2 O (where x = 5), molecular weight of 798.86 g/mol (anhydrous), and structural formula as shown: LEVO-T tablets for oral administration are supplied in the following strengths: 25 mcg, 50 mcg, 75 mcg, 88 mcg, 100 mcg, 112 mcg, 125 mcg, 137 mcg, 150 mcg, 175 mcg, 200 mcg, and 300 mcg. Each LEVO-T tablet contains the inactive ingredients colloidal silicone dioxide, NF; magnesium stearate, NF; microcrystalline cellulose, NF; and sodium starch glycolate, NF. LEVO-T tablets contain no ingredients made from a gluten-containing grain (wheat, barley, or rye). LEVO-T tablets do not contain lactose. Each tablet strength meets USP Dissolution Test 2. Table 9 provides a listing of the color additives by tablet strength: Table 9. LEVO-T Tablets Color Additives Strength (mcg) Color additive(s) 25 FD&C Yellow No. 6 Aluminum Lake 50 None 75 FD&C Blue No. 2 Aluminum Lake, D&C Red No. 27 Aluminum Lake 88 FD&C Blue No. 1 Aluminum Lake, D&C Yellow No. 10 Aluminum Lake, D&C Red No. 30 Aluminum Lake 100 D&C Yellow No. 10 Aluminum Lake, D&C Red Lake Blend (D&C Red No. 27 Lake and D&C Red No. 30 Lake) 112 D&C Red No. 27 Aluminum Lake, D&C Red No. 30 Aluminum Lake 125 FD&C Yellow No. 6 Aluminum Lake, FD&C Red No. 40 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake 137 FD&C Blue No. 1 Aluminum Lake 150 FD&C Blue No. 2 Aluminum Lake 175 D&C Red No. 27 Aluminum Lake, D&C Red No. 30 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake 200 D&C Yellow No. 10 Aluminum Lake, D&C Red No. 27 Aluminum Lake 300 D&C Yellow No. 10 Aluminum Lake, FD&C Yellow No. 6 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake levo molecule
| Strength (mcg) | Color additive(s) |
|---|---|
| 25 | FD&C Yellow No. 6 Aluminum Lake |
| 50 | None |
| 75 | FD&C Blue No. 2 Aluminum Lake, D&C Red No. 27 Aluminum Lake |
| 88 | FD&C Blue No. 1 Aluminum Lake, D&C Yellow No. 10 Aluminum Lake, D&C Red No. 30 Aluminum Lake |
| 100 | D&C Yellow No. 10 Aluminum Lake, D&C Red Lake Blend (D&C Red No. 27 Lake and D&C Red No. 30 Lake) |
| 112 | D&C Red No. 27 Aluminum Lake, D&C Red No. 30 Aluminum Lake |
| 125 | FD&C Yellow No. 6 Aluminum Lake, FD&C Red No. 40 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake |
| 137 | FD&C Blue No. 1 Aluminum Lake |
| 150 | FD&C Blue No. 2 Aluminum Lake |
| 175 | D&C Red No. 27 Aluminum Lake, D&C Red No. 30 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake |
| 200 | D&C Yellow No. 10 Aluminum Lake, D&C Red No. 27 Aluminum Lake |
| 300 | D&C Yellow No. 10 Aluminum Lake, FD&C Yellow No. 6 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake |
Dosage and administration
Information about the drug product’s dosage and administration recommendations, including starting dose, dose range, titration regimens, and any other clinically sigificant information that affects dosing recommendations.2 DOSAGE AND ADMINISTRATION Administer once daily, preferably on an empty stomach, one-half to one hour before breakfast. (2.1) Administer at least 4 hours before or after drugs that are known to interfere with absorption. (2.1) Evaluate the need for dose adjustments when regularly administering within one hour of certain foods that may affect absorption. (2.1) Advise patients to stop biotin and biotin-containing supplements at least 2 days before assessing TSH and/or T4 levels. (2.2) Starting dose depends on a variety of factors, including age, body weight, cardiovascular status, and concomitant medications. Peak therapeutic effect may not be attained for 4-6 weeks. (2.2) See full prescribing information for dosing in specific patient populations. (2.3) Adequacy of therapy determined with periodic monitoring of TSH and/or T4 as well as clinical status. (2.4) 2.1 Important Administration Information Take LEVO-T with a full glass of water as the tablet may rapidly disintegrate. Administer LEVO-T as a single daily dose, on an empty stomach, one-half to one hour before breakfast. Administer LEVO-T at least 4 hours before or after drugs known to interfere with LEVO-T absorption [see Drug Interactions (7.1)] . Evaluate the need for dosage adjustments when regularly administering within one hour of certain foods that may affect LEVO-T absorption [see Dosage and Administration (2.2 and 2.3), Drug Interactions (7.9) and Clinical Pharmacology (12.3)] . Administer LEVO-T to pediatric patients who cannot swallow intact tablets by crushing the tablet, suspending the freshly crushed tablet in a small amount (5 to 10 mL) of water and immediately administering the suspension by spoon or dropper. Ensure the patient ingests the full amount of the suspension. Do not store the suspension. Do not administer in foods that decrease absorption of LEVO-T, such as soybean-based infant formula [see Drug Interactions (7.9)] . 2.2 Important Considerations for Dosing The dosage of LEVO-T 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 (2.3), Warnings and Precautions (5), and Drug Interactions (7)] . Dosing must be individualized to account for these factors and dosage adjustments made based on periodic assessment of the patient's clinical response and laboratory parameters [see Dosage and Administration (2.4)] . For adult patients with primary hypothyroidism, titrate until the patient is clinically euthyroid and the serum TSH returns to normal [see Dosage and Administration (2.3)] . For secondary or tertiary hypothyroidism, serum TSH is not a reliable measure of LEVO-T dosage adequacy and should not be used to monitor therapy. Use the serum free-T4 level to titrate LEVO-T dosing until the patient is clinically euthyroid and the serum free-T4 level is restored to the upper half of the normal range [see Dosage and Administration (2.3)] . Inquire whether patients are taking biotin or biotin-containing supplements. If so, advise them to stop biotin supplementation at least 2 days before assessing TSH and/or T4 levels [see Dosage and Administration (2.4) and Drug Interactions (7.10)] . The peak therapeutic effect of a given dose of LEVO-T may not be attained for 4 to 6 weeks. 2.3 Recommended Dosage and Titration Primary, Secondary, and Tertiary Hypothyroidism in Adults The recommended starting daily dosage of LEVO-T in adults with primary, secondary, or tertiary hypothyroidism is based on age and comorbid cardiac conditions, as described in Table 1. For patients at risk of atrial fibrillation or patients with underlying cardiac disease, start with a lower dosage and titrate the dosage more slowly to avoid exacerbation of cardiac symptoms. Dosage titration is based on serum TSH or free-T4 [see Dosage and Administration (2.2)] . Table 1. LEVO-T Dosing Guidelines for Hypothyroidism in Adults* Patient Population Starting Dosage Dosage Titration Based on Serum TSH or Free-T4 Adults diagnosed with hypothyroidism Full replacement dose is 1.6 mcg/kg/day. Some patients require a lower starting dose. Titrate dosage by 12.5 to 25 mcg increments every 4 to 6 weeks, as needed until the patient is euthyroid. Adults at risk for atrial fibrillation or with underlying cardiac disease Lower starting dose (less than 1.6 mcg/kg/day) Titrate dosage every 6 to 8 weeks, as needed until the patient is euthyroid. Geriatric patients Lower starting dose (less than 1.6 mcg/kg/day) *Dosages greater than 200 mcg/day are seldom required. An inadequate response to daily dosages greater than 300 mcg/day is rare and may indicate poor compliance, malabsorption, drug interactions, or a combination of these factors [see Dosage and Administration (2.1) and Drug Interactions (7)] . Primary, Secondary, and Tertiary Hypothyroidism in Pediatric Patients The recommended starting daily dosage of LEVO-T in pediatric patients with primary, secondary, or tertiary hypothyroidism is based on body weight and changes with age as described in Table 2. Titrate the dosage (every 2 weeks) as needed based on serum TSH or free-T4 until the patient is euthyroid [see Dosage and Administration (2.2)] . Table 2. LEVO-T Dosing Guidelines for Hypothyroidism in Pediatric Patients Age Starting Daily Dosage Per Kg Body Weight* 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 Greater than 12 years but growth and puberty incomplete 2-3 mcg/kg/day Growth and puberty complete 1.6 mcg/kg/day *Adjust dosage based on clinical response and laboratory parameters [see Dosage and Administration (2.4) and Use in Specific Populations (8.4)] . *Adjust dosage based on clinical response and laboratory parameters [see Dosage and Administration (2.4) and Use in Specific Populations (8.4)] . Pediatric Patients from Birth to 3 Months of Age at Risk for Cardiac Failure Start at a lower starting dosage and increase the dosage every 4 to 6 weeks as needed based on clinical and laboratory response. Pediatric Patients at Risk for Hyperactivity To minimize the risk of hyperactivity, start at one-fourth the recommended full replacement dosage, and increase on a weekly basis by one-fourth the full recommended replacement dosage until the full recommended replacement dosage is reached. Hypothyroidism in Pregnant Patients For pregnant patients with pre-existing hypothyroidism, measure serum TSH and free-T4 as soon as pregnancy is confirmed and, at minimum, during each trimester of pregnancy. In pregnant patients with primary hypothyroidism, maintain serum TSH in the trimester-specific reference range. The recommended daily dosage of LEVO-T in pregnant patients is described in Table 3. Table 3. LEVO-T Dosing Guidelines for Hypothyroidism in Pregnant Patients Patient Population Starting Dosage Dose Adjustment and Titration Pre-existing primary hypothyroidism with serum TSH above normal trimester-specific range Pre-pregnancy dosage may increase during pregnancy Increase LEVO-T dosage by 12.5 to 25 mcg per day. Monitor TSH every 4 weeks until a stable dose is reached and serum TSH is within normal trimester-specific range. Reduce LEVO-T dosage to pre-pregnancy levels immediately after delivery. Monitor serum TSH 4 to 8 weeks postpartum. New onset hypothyroidism (TSH ≥ 10 mIU per liter) 1.6 mcg/kg/day Monitor serum TSH every 4 weeks and adjust LEVO-T dosage until serum TSH is within normal trimester specific range. New onset hypothyroidism (TSH < 10 mIU per liter) 1.0 mcg/kg/day TSH Suppression in Well-differentiated Thyroid Cancer in Adult and Pediatric Patients The LEVO-T dosage is based on the target level of TSH suppression for the stage and clinical status of thyroid cancer. 2.4 Monitoring TSH and/or Thyroxine (T4) Levels Assess the adequacy of therapy by periodic assessment of laboratory tests and clinical evaluation. Biotin supplementation may interfere with immunoassays for TSH, T4, and T3, resulting in erroneous thyroid hormone test results. Stop biotin and biotin-containing supplements for at least 2 days before assessing TSH and/or T4 levels [see Drug Interactions (7.10)] . Persistent clinical and laboratory evidence of hypothyroidism despite an apparent adequate replacement dose of LEVO-T 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 levels after an interval of 6 to 8 weeks after any change in dose. In patients on a stable and appropriate replacement dosage, evaluate clinical and biochemical response every 6 to 12 months and whenever there is a change in the patient’s clinical status. Pediatric Patients In patients with hypothyroidism, assess the adequacy of replacement therapy by measuring both serum TSH and total or free-T4. Monitor TSH and total or free-T4 in pediatric patients as follows: 2 and 4 weeks after the initiation of treatment, 2 weeks after any change in dosage, and then every 3 to 12 months thereafter following dosage stabilization until growth is 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. 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 T4 to increase into the upper half of the normal range within 2 weeks of initiation of LEVO-T therapy and/or of the serum TSH to decrease below 20 IU per liter within 4 weeks may indicate the patient is not receiving adequate therapy. Assess compliance, dose of medication administered, and method of administration prior to increasing the dose of LEVO-T [see Warnings and Precautions (5.1) and Use in Specific Populations (8.4)] . Secondary and Tertiary Hypothyroidism Monitor serum free-T4 levels and maintain in the upper half of the normal range in these patients.
| Adults diagnosed with hypothyroidism | Full replacement dose is 1.6 mcg/kg/day. Some patients require a lower starting dose. | Titrate dosage by 12.5 to 25 mcg increments every 4 to 6 weeks, as needed until the patient is euthyroid. |
| Adults at risk for atrial fibrillation or with underlying cardiac disease | Lower starting dose (less than 1.6 mcg/kg/day) | Titrate dosage every 6 to 8 weeks, as needed until the patient is euthyroid. |
| Geriatric patients | Lower starting dose (less than 1.6 mcg/kg/day) |
| 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 |
| 2-3 mcg/kg/day | |
| Growth and puberty complete | 1.6 mcg/kg/day |
| Patient Population | Starting Dosage | Dose Adjustment and Titration |
| Pre-existing primary hypothyroidism with serum TSH above normal trimester-specific range | Pre-pregnancy dosage may increase during pregnancy | |
| 1.6 mcg/kg/day | Monitor serum TSH every 4 weeks and adjust LEVO-T dosage until serum TSH is within normal trimester specific range. | |
| New onset hypothyroidism (TSH < 10 mIU per liter) | 1.0 mcg/kg/day |
Dosage forms and strengths
Information about all available dosage forms and strengths for the drug product to which the labeling applies. This field may contain descriptions of product appearance.3 DOSAGE FORMS AND STRENGTHS LEVO-T tablets are available as follows (Table 4): Table 4. LEVO-T Tablet Strengths and Identifying Features Tablet Strength Tablet Color/Shape Tablet Markings 25 mcg Orange/Caplet "25" and "GG/331" 50 mcg White/ Caplet "50" and "GG/332" 75 mcg Violet/ Caplet "75" and "GG/333" 88 mcg Olive Green/ Caplet "88" and "GG/334" 100 mcg Yellow/ Caplet "100" and "GG/335" 112 mcg Rose/ Caplet "112" and "GG/336" 125 mcg Brown/ Caplet "125" and "GG/337" 137 mcg Turquoise/ Caplet "137" and "GG/330" 150 mcg Blue/ Caplet "150" and "GG/338" 175 mcg Lilac/ Caplet "175" and "GG/339" 200 mcg Pink/ Caplet "200" and "GG/340" 300 mcg Green/ Caplet "300" and "GG/341" Tablets: 25, 50, 75, 88, 100, 112, 125, 137, 150, 175, 200, and 300 mcg (3)
| 25 mcg | Orange/Caplet | "25" and "GG/331" |
| 50 mcg | White/ Caplet | "50" and "GG/332" |
| 75 mcg | Violet/ Caplet | "75" and "GG/333" |
| 88 mcg | Olive Green/ Caplet | "88" and "GG/334" |
| 100 mcg | Yellow/ Caplet | "100" and "GG/335" |
| 112 mcg | Rose/ Caplet | "112" and "GG/336" |
| 125 mcg | Brown/ Caplet | "125" and "GG/337" |
| 137 mcg | Turquoise/ Caplet | "137" and "GG/330" |
| 150 mcg | Blue/ Caplet | "150" and "GG/338" |
| 175 mcg | Lilac/ Caplet | "175" and "GG/339" |
| 200 mcg | Pink/ Caplet | "200" and "GG/340" |
| 300 mcg | Green/ Caplet | "300" and "GG/341" |
Indications and usage
A statement of each of the drug products indications for use, such as for the treatment, prevention, mitigation, cure, or diagnosis of a disease or condition, or of a manifestation of a recognized disease or condition, or for the relief of symptoms associated with a recognized disease or condition. This field may also describe any relevant limitations of use.1 INDICATIONS AND USAGE LEVO-T is L-thyroxine (T4) indicated in adult and pediatric patients, including neonates, for: Hypothyroidism: As replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism. (1) Pituitary Thyrotropin (Thyroid-Stimulating Hormone, TSH) Suppression: As an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer. (1) Limitations of Use Not indicated for suppression of benign thyroid nodules and nontoxic diffuse goiter in iodine-sufficient patients Not indicated for treatment of hypothyroidism during the recovery phase of subacute thyroiditis Hypothyroidism LEVO-T is indicated in adult and pediatric patients, including neonates, as a replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism. Pituitary Thyrotropin (Thyroid-Stimulating Hormone, TSH) Suppression LEVO-T is indicated in adult and pediatric patients, including neonates, as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer. Limitations of Use LEVO-T 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 LEVO-T may induce hyperthyroidism [see Warnings and Precautions (5.1)] . LEVO-T is not indicated for treatment of hypothyroidism during the recovery phase of subacute thyroiditis.
Spl product data elements
Usually a list of ingredients in a drug product.LEVO-T Levothyroxine Sodium D&C RED NO. 27 ALUMINUM LAKE D&C YELLOW NO. 10 SILICON DIOXIDE SODIUM STARCH GLYCOLATE TYPE A POTATO MICROCRYSTALLINE CELLULOSE MAGNESIUM STEARATE LEVOTHYROXINE SODIUM LEVOTHYROXINE LEVOTHYROXINE SODIUM ANHYDROUS 200;GG;340 caplet LEVO-T Levothyroxine Sodium D&C YELLOW NO. 10 FD&C YELLOW NO. 6 FOOD YELLOW 3 FREE ACID FD&C BLUE NO. 1--ALUMINUM LAKE SILICON DIOXIDE SODIUM STARCH GLYCOLATE TYPE A POTATO MICROCRYSTALLINE CELLULOSE MAGNESIUM STEARATE LEVOTHYROXINE SODIUM LEVOTHYROXINE LEVOTHYROXINE SODIUM ANHYDROUS 300;GG;341 caplet LEVO-T Levothyroxine Sodium FD&C BLUE NO. 2--ALUMINUM LAKE SILICON DIOXIDE SODIUM STARCH GLYCOLATE TYPE A POTATO MICROCRYSTALLINE CELLULOSE MAGNESIUM STEARATE LEVOTHYROXINE SODIUM LEVOTHYROXINE LEVOTHYROXINE SODIUM ANHYDROUS 150;GG;338 caplet LEVO-T Levothyroxine Sodium D&C RED NO. 27 ALUMINUM LAKE D&C RED NO. 30 FD&C BLUE NO. 1--ALUMINUM LAKE SILICON DIOXIDE SODIUM STARCH GLYCOLATE TYPE A POTATO MICROCRYSTALLINE CELLULOSE MAGNESIUM STEARATE LEVOTHYROXINE SODIUM LEVOTHYROXINE LEVOTHYROXINE SODIUM ANHYDROUS caplet (lilac) 175;GG;339 LEVO-T Levothyroxine Sodium FD&C BLUE NO. 1--ALUMINUM LAKE SILICON DIOXIDE SODIUM STARCH GLYCOLATE TYPE A POTATO MAGNESIUM STEARATE MICROCRYSTALLINE CELLULOSE LEVOTHYROXINE SODIUM LEVOTHYROXINE LEVOTHYROXINE SODIUM ANHYDROUS 137;GG;330 Caplet LEVO-T Levothyroxine Sodium FD&C RED NO. 40 FD&C YELLOW NO. 6 FOOD YELLOW 3 FREE ACID FD&C BLUE NO. 1--ALUMINUM LAKE SILICON DIOXIDE SODIUM STARCH GLYCOLATE TYPE A POTATO MICROCRYSTALLINE CELLULOSE MAGNESIUM STEARATE LEVOTHYROXINE SODIUM LEVOTHYROXINE LEVOTHYROXINE SODIUM ANHYDROUS 125;GG;337 caplet LEVO-T Levothyroxine Sodium LEVOTHYROXINE SODIUM LEVOTHYROXINE LEVOTHYROXINE SODIUM ANHYDROUS SODIUM STARCH GLYCOLATE TYPE A POTATO SILICON DIOXIDE MICROCRYSTALLINE CELLULOSE MAGNESIUM STEARATE Caplet 50;GG;332 LEVO-T Levothyroxine Sodium FD&C BLUE NO. 2--ALUMINUM LAKE D&C RED NO. 27 ALUMINUM LAKE SODIUM STARCH GLYCOLATE TYPE A POTATO SILICON DIOXIDE MAGNESIUM STEARATE MICROCRYSTALLINE CELLULOSE LEVOTHYROXINE SODIUM LEVOTHYROXINE LEVOTHYROXINE SODIUM ANHYDROUS (violet) 75;GG;333 Caplet LEVO-T Levothyroxine Sodium FD&C YELLOW NO. 6 FOOD YELLOW 3 FREE ACID MAGNESIUM STEARATE SILICON DIOXIDE MICROCRYSTALLINE CELLULOSE SODIUM STARCH GLYCOLATE TYPE A POTATO LEVOTHYROXINE SODIUM LEVOTHYROXINE LEVOTHYROXINE SODIUM ANHYDROUS caplet 25;GG;331 LEVO-T Levothyroxine Sodium D&C RED NO. 27 D&C YELLOW NO. 10 D&C RED NO. 30 SODIUM STARCH GLYCOLATE TYPE A POTATO MICROCRYSTALLINE CELLULOSE MAGNESIUM STEARATE SILICON DIOXIDE LEVOTHYROXINE SODIUM LEVOTHYROXINE LEVOTHYROXINE SODIUM ANHYDROUS 100;GG;335 Caplet LEVO-T Levothyroxine Sodium FD&C BLUE NO. 1--ALUMINUM LAKE D&C YELLOW NO. 10 D&C RED NO. 30 MICROCRYSTALLINE CELLULOSE MAGNESIUM STEARATE SODIUM STARCH GLYCOLATE TYPE A POTATO SILICON DIOXIDE LEVOTHYROXINE SODIUM LEVOTHYROXINE LEVOTHYROXINE SODIUM ANHYDROUS (olive) 88;GG;334 caplet LEVO-T Levothyroxine Sodium D&C RED NO. 30 D&C RED NO. 27 ALUMINUM LAKE MICROCRYSTALLINE CELLULOSE MAGNESIUM STEARATE SILICON DIOXIDE SODIUM STARCH GLYCOLATE TYPE A POTATO LEVOTHYROXINE SODIUM LEVOTHYROXINE LEVOTHYROXINE SODIUM ANHYDROUS (Rose) 112;GG;336 caplet
Carcinogenesis and mutagenesis and impairment of fertility
Information about carcinogenic, mutagenic, or fertility impairment potential revealed by studies in animals. Information from human data about such potential is part of the warnings field.13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term carcinogenicity studies in animals to evaluate the carcinogenic potential of levothyroxine have not been performed. Studies to evaluate mutagenic potential and animal fertility have not been performed.
Nonclinical toxicology
Information about toxicology in non-human subjects.13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Long-term carcinogenicity studies in animals to evaluate the carcinogenic potential of levothyroxine have not been performed. Studies to evaluate mutagenic potential and animal fertility have not been performed.
Package label principal display panel
The content of the principal display panel of the product package, usually including the product’s name, dosage forms, and other key information about the drug product.Principal Display Panel levo 25 mcg 90 Levo 25 mcg 1000 Levo 50 mcg 90 Levo 50 mcg 1000 Levo 75 mcg 90 Levo 75 mcg 1000 Levo 88 mcg 90 Levo 88 mcg 1000 Levo 100 mcg 90 Levo 100 mcg 1000 Levo 112 mcg 90 Levo 112 mcg 1000 Levo 125 mcg 90 Levo 125 mcg 1000 Levo 137 mcg 90 Levo 137 mcg 1000 Levo 150 mcg 90 Levo 150 mcg 1000 Levo 175 mcg 90 Levo 175 mcg 1000 Levo 200 mcg 90 Levo 200 mcg 1000 Levo 300 mcg 90 Levo 300 mcg 1000 Levo molecule
LEVO-T: Information for patients
Information necessary for patients to use the drug safely and effectively, such as precautions concerning driving or the concomitant use of other substances that may have harmful additive effects.17 PATIENT COUNSELING INFORMATION Inform the patient of the following information to aid in the safe and effective use of LEVO-T: Dosing and Administration Instruct patients that LEVO-T should be taken with a full glass of water since the tablet may rapidly disintegrate. Instruct patients to take LEVO-T only as directed by their healthcare provider. Instruct patients to take LEVO-T as a single dose, preferably on an empty stomach, one-half to one hour before breakfast. Inform patients that agents such as iron and calcium supplements and antacids can decrease the absorption of levothyroxine. Instruct patients not to take LEVO-T tablets within 4 hours of these agents. Instruct patients to notify their healthcare provider if they are pregnant or breastfeeding or are thinking of becoming pregnant while taking LEVO-T. Important Information Inform patients that it may take several weeks before they notice an improvement in symptoms. Inform patients that the levothyroxine in LEVO-T 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 LEVO-T 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 discontinue biotin or any biotin-containing supplements for at least 2 days before thyroid function testing is conducted. Instruct patients to notify their physician of any other medical conditions they may have, 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 they are taking LEVO-T. If they have diabetes, instruct patients to monitor their blood and/or urinary glucose levels as directed by their physician and immediately report any changes to their physician. If patients are taking anticoagulants, their clotting status should be checked frequently. Instruct patients to notify their physician or dentist that they are taking LEVO-T 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. Inform patients that partial hair loss may occur rarely during the first few months of LEVO-T therapy, but this is usually temporary. Manufactured and Distributed by: Neolpharma, Inc. Caguas, Puerto Rico 00725 PP10403
Geriatric use
Information about any limitations on any geriatric indications, needs for specific monitoring, hazards associated with use of the drug in the geriatric population.8.5 Geriatric Use Because of the increased prevalence of cardiovascular disease among the elderly, initiate LEVO-T at less than the full replacement dose [see Dosage and Administration (2.3) and Warnings and Precautions (5.2)] . Atrial arrhythmias can occur in elderly patients. Atrial fibrillation is the most common of the arrhythmias observed with levothyroxine overtreatment in the elderly.
Pediatric use
Information about any limitations on any pediatric indications, needs for specific monitoring, hazards associated with use of the drug in any subsets of the pediatric population (such as neonates, infants, children, or adolescents), differences between pediatric and adult responses to the drug, and other information related to the safe and effective pediatric use of the drug.8.4 Pediatric Use LEVO-T is indicated in patients from birth to less than 17 years of age: As a replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism. As an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer Rapid restoration of normal serum T4 concentrations is essential for preventing the adverse effects of congenital hypothyroidism on cognitive development as well as on overall physical growth and maturation. Therefore, initiate LEVO-T therapy immediately upon diagnosis. Levothyroxine is generally continued for life in these patients [see Warnings and Precautions (5.1)] . Closely monitor infants during the first 2 weeks of LEVO-T therapy for cardiac overload and arrhythmias. Congenital Hypothyroidism [See Dosage and Administration (2.3 , 2.4) ] 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 LEVO-T therapy immediately upon diagnosis. Levothyroxine is generally continued for life in these patients. Closely monitor infants during the first 2 weeks of LEVO-T 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. 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.
Pregnancy
Information about effects the drug may have on pregnant women or on a fetus. This field may be ommitted if the drug is not absorbed systemically and the drug is not known to have a potential for indirect harm to the fetus. It may contain information about the established pregnancy category classification for the drug. (That information is nominally listed in the teratogenic_effects field, but may be listed here instead.)8.1 Pregnancy Risk Summary The clinical experience, including data from postmarketing studies, in pregnant women treated with oral levothyroxine to maintain euthyroid state have not reported increased rates of major birth defects, miscarriages, or other adverse maternal or fetal outcomes. 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 LEVO-T dosage adjusted during pregnancy ( see Clinical Considerations ). Animal reproductive studies have not been conducted with levothyroxine sodium. LEVO-T 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. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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 LEVO-T requirements. Serum TSH levels should be monitored and the LEVO-T dosage adjusted during pregnancy. Since postpartum TSH levels are similar to preconception values, the LEVO-T dosage should return to the pre-pregnancy dose immediately after delivery [see Dosage and Administration (2.3)] . 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 LEVO-T requirements. Serum TSH levels should be monitored and the LEVO-T dosage adjusted during pregnancy. Since postpartum TSH levels are similar to preconception values, the LEVO-T dosage should return to the pre-pregnancy dose immediately after delivery [see Dosage and Administration (2.3) ]. Data Human Data Levothyroxine is approved for use as a replacement therapy for hypothyroidism. There is a long experience of levothyroxine use in pregnant women, including data from post-marketing studies that have not reported increased rates of fetal malformations, miscarriages or other adverse maternal or fetal outcomes associated with levothyroxine use in pregnant women.
Use in specific populations
Information about use of the drug by patients in specific populations, including pregnant women and nursing mothers, pediatric patients, and geriatric patients.8 USE IN SPECIFIC POPULATIONS Pregnancy may require the use of higher doses of LEVO-T. ( 2.3 , 8.1 ) 8.1 Pregnancy Risk Summary The clinical experience, including data from postmarketing studies, in pregnant women treated with oral levothyroxine to maintain euthyroid state have not reported increased rates of major birth defects, miscarriages, or other adverse maternal or fetal outcomes. 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 LEVO-T dosage adjusted during pregnancy ( see Clinical Considerations ). Animal reproductive studies have not been conducted with levothyroxine sodium. LEVO-T 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. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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 LEVO-T requirements. Serum TSH levels should be monitored and the LEVO-T dosage adjusted during pregnancy. Since postpartum TSH levels are similar to preconception values, the LEVO-T dosage should return to the pre-pregnancy dose immediately after delivery [see Dosage and Administration (2.3)] . 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 LEVO-T requirements. Serum TSH levels should be monitored and the LEVO-T dosage adjusted during pregnancy. Since postpartum TSH levels are similar to preconception values, the LEVO-T dosage should return to the pre-pregnancy dose immediately after delivery [see Dosage and Administration (2.3) ]. Data Human Data Levothyroxine is approved for use as a replacement therapy for hypothyroidism. There is a long experience of levothyroxine use in pregnant women, including data from post-marketing studies that have not reported increased rates of fetal malformations, miscarriages or other adverse maternal or fetal outcomes associated with levothyroxine use in pregnant women. 8.2 Lactation Risk Summary Published studies report that levothyroxine is present in human milk following the administration of oral levothyroxine. No adverse effects on the breastfed infant have been reported and there is no information on the effects of levothyroxine on milk production. Adequate levothyroxine treatment during lactation may normalize milk production in hypothyroid lactating mothers with low milk supply. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for LEVO-T and any potential adverse effects on the breastfed infant from LEVO-T or from the underlying maternal condition. 8.4 Pediatric Use LEVO-T is indicated in patients from birth to less than 17 years of age: As a replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism. As an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer Rapid restoration of normal serum T4 concentrations is essential for preventing the adverse effects of congenital hypothyroidism on cognitive development as well as on overall physical growth and maturation. Therefore, initiate LEVO-T therapy immediately upon diagnosis. Levothyroxine is generally continued for life in these patients [see Warnings and Precautions (5.1)] . Closely monitor infants during the first 2 weeks of LEVO-T therapy for cardiac overload and arrhythmias. Congenital Hypothyroidism [See Dosage and Administration (2.3 , 2.4) ] 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 LEVO-T therapy immediately upon diagnosis. Levothyroxine is generally continued for life in these patients. Closely monitor infants during the first 2 weeks of LEVO-T 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. 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. 8.5 Geriatric Use Because of the increased prevalence of cardiovascular disease among the elderly, initiate LEVO-T at less than the full replacement dose [see Dosage and Administration (2.3) and Warnings and Precautions (5.2)] . Atrial arrhythmias can occur in elderly patients. Atrial fibrillation is the most common of the arrhythmias observed with levothyroxine overtreatment in the elderly.
How supplied
Information about the available dosage forms to which the labeling applies, and for which the manufacturer or distributor is responsible. This field ordinarily includes the strength of the dosage form (in metric units), the units in which the dosage form is available for prescribing, appropriate information to facilitate identification of the dosage forms (such as shape, color, coating, scoring, and National Drug Code), and special handling and storage condition information.16 HOW SUPPLIED/STORAGE AND HANDLING How Supplied LEVO-T (levothyroxine sodium, USP) tablets are supplied as follows (Table 11): Table 11. LEVO-T Tablet Presentations Strength (mcg) Color/Shape Tablet Markings NDC# for bottles of 90 NDC # for bottles of 1000 25 Orange/Caplet "25" and "GG/331" 55466-104-11 55466-104-19 50 White/ Caplet "50" and "GG/332" 55466-105-11 55466-105-19 75 Violet/ Caplet "75" and "GG/333" 55466-106-11 55466-106-19 88 Olive Green/ Caplet "88" and 'GG/334" 55466-107-11 5466-107-19 100 Yellow/ Caplet "100" and "GG/335" 55466-108-11 55466-108-19 112 Rose/ Caplet "112" and "GG/336" 55466-109-11 55466-109-19 125 Brown/ Caplet "125" and "GG/337" 55466-110-11 55466-110-19 137 Turquoise/ Caplet "137" and "GG/330" 55466-111-11 55466-111-19 150 Blue/ Caplet "150" and "GG/338" 55466-112-11 55466-112-19 175 Lilac/ Caplet "175" and "GG/339" 55466-113-11 55466-113-19 200 Pink/ Caplet "200" and "GG/340" 55466-114-11 55466-114-19 300 Green/ Caplet "300" and "GG/341" 55466-115-11 55466-115-19 Storage and Handling Store LEVO-T at 25°C (77°F); excursions permitted to 15° to 30° C (59° to 86° F) (see USP Controlled Room Temperature). LEVO-T tablets should be protected from light and moisture.
| Strength (mcg) | Color/Shape | Tablet Markings | NDC# for bottles of 90 | NDC # for bottles of 1000 |
|---|---|---|---|---|
| 25 | Orange/Caplet | "25" and "GG/331" | 55466-104-11 | 55466-104-19 |
| 50 | White/ Caplet | "50" and "GG/332" | 55466-105-11 | 55466-105-19 |
| 75 | Violet/ Caplet | "75" and "GG/333" | 55466-106-11 | 55466-106-19 |
| 88 | Olive Green/ Caplet | "88" and 'GG/334" | 55466-107-11 | 5466-107-19 |
| 100 | Yellow/ Caplet | "100" and "GG/335" | 55466-108-11 | 55466-108-19 |
| 112 | Rose/ Caplet | "112" and "GG/336" | 55466-109-11 | 55466-109-19 |
| 125 | Brown/ Caplet | "125" and "GG/337" | 55466-110-11 | 55466-110-19 |
| 137 | Turquoise/ Caplet | "137" and "GG/330" | 55466-111-11 | 55466-111-19 |
| 150 | Blue/ Caplet | "150" and "GG/338" | 55466-112-11 | 55466-112-19 |
| 175 | Lilac/ Caplet | "175" and "GG/339" | 55466-113-11 | 55466-113-19 |
| 200 | Pink/ Caplet | "200" and "GG/340" | 55466-114-11 | 55466-114-19 |
| 300 | Green/ Caplet | "300" and "GG/341" | 55466-115-11 | 55466-115-19 |
Storage and handling
Information about safe storage and handling of the drug product.Storage and Handling Store LEVO-T at 25°C (77°F); excursions permitted to 15° to 30° C (59° to 86° F) (see USP Controlled Room Temperature). LEVO-T tablets should be protected from light and moisture.
Boxed warning
Information about contraindications or serious warnings, particularly those that may lead to death or serious injury.WARNING: NOT FOR TREATMENT OF OBESITY OR FOR WEIGHT LOSS WARNING: NOT FOR TREATMENT OF OBESITY OR FOR WEIGHT LOSS Thyroid hormones, including LEVO-T, 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)] . WARNING: NOT FOR TREATMENT OF OBESITY OR FOR WEIGHT LOSS See full prescribing information for complete boxed warning Thyroid hormones, including LEVO-T, 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, 10).
Disclaimer: Do not rely on openFDA or Phanrmacy Near Me to make decisions regarding medical care. While we make every effort to ensure that data is accurate, you should assume all results are unvalidated. Source: OpenFDA, Healthporta Drugs API