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Tips for Knowing Your LEVOXYL Take note of your specific LEVOXYL dose LEVOXYL tablets can be identified by their unique thyroid shape and are color coded by strength. Print and fill out this form to take to the pharmacy so you can make sure you get the brand your doctor has prescribed. My LEVOXYL dosage(s) strength(s): My LEVOXYL tablet color(s): Circle the dosage(s) strength(s) you've been prescribed and check to make sure you have received the correct strengths and colors at the pharmacy.
Stand By Your Brand Generic substitution is possible at the pharmacy Make sure your doctor indicates "No Substitutions" on your prescription; otherwise the pharmacy may switch you to a generic equivalent. Below are TIPS to help you get brand-name LEVOXYL: Take the prescription that your doctor gave you with the following indicated on it: "No Substitutions," T "Dispense As Written (DAW)," or "Brand Medically Necessary," depending on the state you live in I Inform your pharmacist that you prefer, and your doctor has prescribed, brand-name LEVOXYL Pick up your prescription and make sure the bottle label says LEVOXYL—look for the unique P shape of your LEVOXYL tablet S Speak to the pharmacist right away if you do not receive LEVOXYL IndicationsLEVOXYL is used as replacement or supplemental therapy in low thyroid function (hypothyroidism) of any cause, except transient hypothyroidism during the recovery phase of subacute thyroiditis. It is also used in the treatment or prevention of certain types of goiters and, as additional therapy, in the management of a specific thyroid cancer.
Important Safety Information WARNING: You should not use thyroid hormone, including LEVOXYL, alone or with other drugs to treat obesity or for weight loss. The normal daily doses of thyroid hormone are not effective for weight loss if your thyroid function is normal. If you take larger-than-normal doses of thyroid hormone you may get serious or even life-threatening side effects, particularly if you also take certain stimulant weight loss drugs.
Please see Important Safety Information on the following page, and accompanying full Prescribing Information, including BOXED WARNING.
Important Safety Information (continued) You should not use LEVOXYL:• If you have untreated or known overactive thyroid of any cause, heart attack or untreated low adrenal gland function.
• If you are allergic to any of the inactive ingredients in the tablets. Notify your physician if you experience hives, itching, rash, flushing, swelling of the throat, abdominal pain, nausea, vomiting, diarrhea, fever, joint pain, or wheezing, as these may be the symptoms of an allergic reaction.
• For the treatment of male or female infertility unless this condition is due to low thyroid function.
• In a certain type of goiter or for thyroid small masses (particularly in the elderly or those with heart and blood vessel disease), if the TSH level is already lowered. If the TSH level is not lowered, LEVOXYL should be used with caution.
To avoid under- or over-treatment with LEVOXYL, carefully follow the dosage instructions given by your health care provider. Do not discontinue or change the amount you take or how often you take it, unless directed to do so by your physician. Because many drugs interact with levothyroxine sodium, your doctor may need to make adjustments in dosing to maintain therapeutic response.
Long-term therapy with LEVOXYL, especially in women after menopause may decrease bone mineral density.
Tell your physician if you are allergic to any foods or medicines, are pregnant or intend to become pregnant, are breast-feeding or are taking any other medications, including prescription and over-the-counter preparations. If you become pregnant while taking LEVOXYL, it is likely that your dose will need to be increased while you are pregnant.
Tell your physician of any other medical conditions you may have, particularly heart disease, diabetes, clotting disorders, and adrenal or pituitary gland problems. Your dose of medications used to control these other conditions may need to be adjusted while you are taking LEVOXYL.
While taking LEVOXYL, there is a risk of high blood pressure, heart failure, heart attack, and cardiac arrest, as well as growth changes in children.
Tell your physician if you experience any of the following adverse events, or any other unusual medical events: • Rapid or irregular heartbeat • Excessive sweating • Sleeplessness • Heat intolerance • Shortness of breath • Change in appetite • Changes in menstrual periods • Weight gain or loss • Hives or skin rash • Partial temporary hair loss Take LEVOXYL in the morning on an empty stomach, at least one-half hour before eating any food. It is very important that you take the tablet with a full glass of water to avoid choking, gagging, tablet getting stuck in your throat or difficulty swallowing.
You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.fda.gov/medwatch or call 1-800-FDA-1088.
Please see accompanying full Prescribing Information, including BOXED WARNING. LEV765806-01 2015 Pfizer Inc. All rights reserved. August 2015 INDICATIONS AND USAGE
(levothyroxine sodium tablets, USP)
Levothyroxine sodium is used for the following indications: Hypothyroidism — As replacement or supplemental therapy in congenital or acquired hypothyroidism of any etiology,
except transient hypothyroidism during the recovery phase of subacute thyroiditis. Specific indications include: primary – LEVOXYL® (levothyroxine sodium tablets, USP) contain synthetic crystalline L-3,3',5,5'-tetraiodothyronine sodium (thyroidal), secondary (pituitary), and tertiary (hypothalamic) hypothyroidism and subclinical hypothyroidism. Primary salt [levothyroxine (T4) sodium]. Synthetic T4 is identical to that produced in the human thyroid gland. Levothyroxine hypothyroidism may result from functional deficiency, primary atrophy, partial or total congenital absence of the thyroid gland, or from the effects of surgery, radiation, or drugs, with or without the presence of goiter.
4) sodium has an empirical formula of C15H10I4N NaO4 • H2O, molecular weight of 798.86 g/mol (anhydrous), and structural formula as shown: Pituitary TSH Suppression — In the treatment or prevention of various types of euthyroid goiters (see WARNINGS
and PRECAUTIONS), including thyroid nodules (see WARNINGS and PRECAUTIONS), subacute or chronic lymphocytic
thyroiditis (Hashimoto's thyroiditis), multinodular goiter (see WARNINGS and PRECAUTIONS) and, as an adjunct to
surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer.
CONTRAINDICATIONS
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 Microcrystalline cellulose, croscarmellose sodium, magnesium stearate, calcium sulfate dihydrate and sodium is contraindicated in patients with uncorrected adrenal insufficiency since thyroid hormones may precipitate an bicarbonate. The following are the coloring additives per tablet strength: acute adrenal crisis by increasing the metabolic clearance of glucocorticoids (see PRECAUTIONS). LEVOXYL® is
contraindicated in patients with hypersensitivity to any of the inactive ingredients in LEVOXYL® tablets (see DESCRIPTION,
Strength
Color additive(s)
FD&C Yellow No. 6 Aluminum Lake WARNING: Thyroid hormones, including LEVOXYL®, 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
FD&C Blue No. 1 Aluminum Lake, D&C Red No. 30 Aluminum Lake hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life
FD&C Yellow No. 6 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake, D&C Yellow No. 10 Aluminum Lake threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines
FD&C Yellow No. 6 Aluminum Lake, D&C Yellow No. 10 Aluminum Lake such as those used for their anorectic effects.
FD&C Yellow No. 6 Aluminum Lake, FD&C Red No. 40 Aluminum Lake, D&C Red No. 30 Aluminum Lake Levothyroxine sodium should not be used in the treatment of male or female infertility unless this condition is associated FD&C Red No. 40 Aluminum Lake, D&C Yellow No. 10 Aluminum Lake FD&C Blue No. 1 Aluminum Lake In patients with nontoxic diffuse goiter or nodular thyroid disease, particularly the elderly or those with underlying FD&C Blue No. 1 Aluminum Lake, D&C Red No. 30 Aluminum Lake cardiovascular disease, levothyroxine sodium therapy is contraindicated if the serum TSH level is already suppressed FD&C Blue No. 1 Aluminum Lake, D&C Yellow No. 10 Aluminum Lake due to the risk of precipitating overt thyrotoxicosis (see CONTRAINDICATIONS). If the serum TSH level is not suppressed,
D&C Red No. 30 Aluminum Lake, D&C Yellow No. 10 Aluminum Lake LEVOXYL® 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 Thyroid hormone synthesis and secretion is regulated by the hypothalamic-pituitary-thyroid axis. Thyrotropin-releasing hormone (TRH) released from the hypothalamus stimulates secretion of thyroid-stimulating hormone, TSH, from the anterior pituitary. TSH, in turn, is the physiologic stimulus for the synthesis and secretion of thyroid hormones, Levothyroxine has a narrow therapeutic index. Regardless of the indication for use, careful dosage titration is L-thyroxine (T4) and L-triiodothyronine (T3), by the thyroid gland. Circulating serum T3 and T4 levels exert a feedback necessary to avoid the consequences of over- or under-treatment. These consequences include, among others, effects effect on both TRH and TSH secretion. When serum T3 and T4 levels increase, TRH and TSH secretion decrease. When on growth and development, cardiovascular function, bone metabolism, reproductive function, cognitive function, thyroid hormone levels decrease, TRH and TSH secretion increase.
emotional state, gastrointestinal function, and on glucose and lipid metabolism. Many drugs interact with levothyroxine The mechanisms by which thyroid hormones exert their physiologic actions are not completely understood, but it is sodium necessitating adjustments in dosing to maintain therapeutic response (see Drug Interactions).
thought that their principal effects are exerted through control of DNA transcription and protein synthesis. T3 and T4 Effects on bone mineral density — In women, long-term levothyroxine sodium therapy has been associated with
diffuse into the cell nucleus and bind to thyroid receptor proteins attached to DNA. This hormone nuclear receptor decreased bone mineral density, especially in postmenopausal women on greater than replacement doses or in women complex activates gene transcription and synthesis of messenger RNA and cytoplasmic proteins.
who are receiving suppressive doses of levothyroxine sodium. Therefore, it is recommended that patients receiving levothyroxine sodium be given the minimum dose necessary to achieve the desired clinical and biochemical response.
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 Patients with underlying cardiovascular disease — Exercise caution when administering levothyroxine to patients
augmentation of cellular respiration and thermogenesis, as well as metabolism of proteins, carbohydrates and lipids. with cardiovascular disorders and to the elderly in whom there is an increased risk of occult cardiac disease. In these The protein anabolic effects of thyroid hormones are essential to normal growth and development.
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).
The physiologic actions of thyroid hormones are produced predominately by T3, the majority of which (approximately If cardiac symptoms develop or worsen, the levothyroxine dose should be reduced or withheld for one week and then 80%) is derived from T4 by deiodination in peripheral tissues.
cautiously restarted at a lower dose. Overtreatment with levothyroxine sodium may have adverse cardiovascular Levothyroxine, at doses individualized according to patient response, is effective as replacement or supplemental effects such as an increase in heart rate, cardiac wall thickness, and cardiac contractility and may precipitate angina therapy in hypothyroidism of any etiology, except transient hypothyroidism during the recovery phase of subacute 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 Levothyroxine is also effective in the suppression of pituitary TSH secretion in the treatment or prevention of various coronary artery disease may precipitate coronary insufficiency.
types of euthyroid goiters, including thyroid nodules, Hashimoto's thyroiditis, multinodular goiter and, as adjunctive Patients with nontoxic diffuse goiter or nodular thyroid disease — Exercise caution when administering
therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer (see INDICATIONS AND
levothyroxine to patients with nontoxic diffuse goiter or nodular thyroid disease in order to prevent precipitation of USAGE, PRECAUTIONS, DOSAGE AND ADMINISTRATION).
thyrotoxicosis (see WARNINGS). If the serum TSH is already suppressed, levothyroxine sodium should not be
administered (see CONTRAINDICATIONS).
Absorption — Absorption of orally administered T
Associated endocrine disorders
4 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 Hypothalamic/pituitary hormone deficiencies — In patients with secondary or tertiary hypothyroidism, additional LEVOXYL® tablets, compared to an equal nominal dose of oral levothyroxine sodium solution, is approximately 98%. hypothalamic/pituitary hormone deficiencies should be considered, and, if diagnosed, treated (see PRECAUTIONS,
T4 absorption is increased by fasting, and decreased in malabsorption syndromes and by certain foods such as Autoimmune polyglandular syndrome) for adrenal insufficiency.
soybean infant formula. Dietary fiber decreases bioavailability of T4. Absorption may also decrease with age. In addition, Autoimmune polyglandular syndrome — Occasionally, chronic autoimmune thyroiditis may occur in association with many drugs and foods affect T4 absorption (see PRECAUTIONS, Drug Interactions and Drug-Food Interactions ).
other autoimmune disorders such as adrenal insufficiency, pernicious anemia, and insulin-dependent diabetes mellitus. Distribution — Circulating thyroid hormones are greater than 99% bound to plasma proteins, including thyroxine-
Patients with concomitant adrenal insufficiency should be treated with replacement glucocorticoids prior to initiation binding globulin (TBG), thyroxine-binding prealbumin (TBPA), and albumin (TBA), whose capacities and affinities vary of treatment with levothyroxine sodium. Failure to do so may precipitate an acute adrenal crisis when thyroid hormone for each hormone. The higher affinity of both TBG and TBPA for T therapy is initiated, due to increased metabolic clearance of glucocorticoids by thyroid hormone. Patients with diabetes 4 partially explains the higher serum levels, slower metabolic clearance, and longer half-life of T mellitus may require upward adjustments of their antidiabetic therapeutic regimens when treated with levothyroxine 4 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 (see PRECAUTIONS, Drug Interactions).
physiologic conditions affect the binding of thyroid hormones to serum proteins (see PRECAUTIONS, Drug Interactions
Other associated medical conditions
and Drug-Laboratory Test Interactions). Thyroid hormones do not readily cross the placental barrier (see
Infants 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 Metabolism — T
common association.
4 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 Information for Patients
monodeiodination. The liver is the major site of degradation for both T4 and T3, with T4 deiodination also occurring Patients should be informed of the following information to aid in the safe and effective use of LEVOXYL®: at a number of additional sites, including the kidney and other tissues. Approximately 80% of the daily dose of T4 is Notify your physician if you are allergic to any foods or medicines, are pregnant or intend to become deiodinated to yield equal amounts of T3 and reverse T3 (rT3). T3 and rT3 are further deiodinated to diiodothyronine. pregnant, are breast-feeding or are taking any other medications, including prescription and over-the- Thyroid hormones are also metabolized via conjugation with glucuronides and sulfates and excreted directly into the bile and gut where they undergo enterohepatic recirculation.
Notify your physician of any other medical conditions you may have, particularly heart disease, diabetes, Elimination — Thyroid hormones are primarily eliminated by the kidneys. A portion of the conjugated hormone
clotting disorders, and adrenal or pituitary gland problems. Your dose of medications used to control these reaches the colon unchanged and is eliminated in the feces. Approximately 20% of T other conditions may need to be adjusted while you are taking LEVOXYL®. If you have diabetes, monitor 4 is eliminated in the stool. Urinary excretion of T your blood and/or urinary glucose levels as directed by your physician and immediately report any 4 decreases with age.
changes to your physician. If you are taking anticoagulants (blood thinners), your clotting status should Table 1: Pharmacokinetic Parameters of Thyroid Hormones in Euthyroid Patients
be checked frequently.
Use LEVOXYL® only as prescribed by your physician. Do not discontinue or change the amount you take or Protein Binding (%)2 how often you take it, unless directed to do so by your physician.
Levothyroxine (T The levothyroxine in LEVOXYL® is intended to replace a hormone that is normally produced by your thyroid gland. Generally, replacement therapy is to be taken for life, except in cases of transient hypothyroidism, which is usually associated with an inflammation of the thyroid gland (thyroiditis).
13 to 4 days in hyperthyroidism, 9 to 10 days in hypothyroidism; 2Includes TBG, TBPA, and TBA Take LEVOXYL® in the morning on an empty stomach, at least one-half hour before eating any food.
LEVOXYL® may rapidly swell and disintegrate resulting in choking, gagging, the tablet getting stuck in Table 2: Drug — Thyroidal Axis Interactions (cont'd)
your throat or difficulty swallowing. It is very important that you take the tablet with a full glass of water. Most of these problems disappeared when Levoxyl® tablets were taken with water.
Drug or Drug Class
It may take several weeks before you notice an improvement in your symptoms.
Drugs that may decrease T4 absorption, which may result in hypothyroidism
Notify your physician if you experience any of the following symptoms: rapid or irregular heartbeat, chest Concurrent use may reduce the efficacy of levothyroxine by binding and delaying or pain, shortness of breath, leg cramps, headache, nervousness, irritability, sleeplessness, tremors, change - Aluminum & Magnesium preventing absorption, potentially resulting in hypothyroidism. Calcium carbonate in appetite, weight gain or loss, vomiting, diarrhea, excessive sweating, heat intolerance, fever, changes in may form an insoluble chelate with levothyroxine, and ferrous sulfate likely forms a menstrual periods, hives or skin rash, or any other unusual medical event.
ferric-thyroxine complex. Administer levothyroxine at least 4 hours apart from these Notify your physician if you become pregnant while taking LEVOXYL®. It is likely that your dose of Bile Acid Sequestrants agents. Patients treated concomitantly with orlistat and levothyroxine should be LEVOXYL® will need to be increased while you are pregnant.
monitored for changes in thyroid function.
10. Notify your physician or dentist that you are taking LEVOXYL® prior to any surgery.
Calcium Carbonate 11. Partial hair loss may occur rarely during the first few months of LEVOXYL® therapy, but this is usually Cation Exchange Resins 12. LEVOXYL® should not be used as a primary or adjunctive therapy in a weight control program.
13. Keep LEVOXYL® out of the reach of children. Store LEVOXYL® away from heat, moisture, and light.
Drugs that may alter T
4 and T3 serum transport — but FT4 concentration remains normal;
and, therefore, the patient remains euthyroid
The diagnosis of hypothyroidism is confirmed by measuring TSH levels using a sensitive assay (second generation Drugs that may increase
Drugs that may decrease
assay sensitivity ≤0.1 mIU/L or third generation assay sensitivity ≤0.01 mIU/L) and measurement of free-T4.
serum TBG concentration
serum TBG concentration
The adequacy of therapy is determined by periodic assessment of appropriate laboratory tests and clinical evaluation. Androgens / Anabolic Steroids The choice of laboratory tests depends on various factors including the etiology of the underlying thyroid disease, Estrogen-containing oral the presence of concomitant medical conditions, including pregnancy, and the use of concomitant medications (see PRECAUTIONS, Drug Interactions
and Drug-Laboratory Test Interactions). Persistent clinical and laboratory
evidence of hypothyroidism despite an apparent adequate replacement dose of LEVOXYL ® may be evidence of Slow-Release Nicotinic Acid inadequate absorption, poor compliance, drug interactions, or decreased T Heroin / Methadone 4 potency of the drug product.
In adult patients with primary (thyroidal) hypothyroidism, serum TSH levels (using a sensitive assay) alone may be used to monitor therapy. The frequency of TSH monitoring during levothyroxine dose titration depends on the clinical Drugs that may cause protein-binding site displacement
situation but it is generally recommended at 6—8 week intervals until normalization. For patients who have recently initiated levothyroxine therapy and whose serum TSH has normalized or in patients who have had their dosage or Furosemide ( > 80 mg IV) Administration of these agents with levothyroxine results in an initial transient brand of levothyroxine changed, the serum TSH concentration should be measured after 8—12 weeks. When the increase in FT4. Continued administration results in a decrease in serum T4 and optimum replacement dose has been attained, clinical (physical examination) and biochemical monitoring may be normal FT4 and TSH concentrations and, therefore, patients are clinically euthyroid. performed every 6—12 months, depending on the clinical situation, and whenever there is a change in the patient's Salicylates inhibit binding of T4 and T3 to TBG and transthyretin. An initial increase in status. It is recommended that a physical examination and a serum TSH measurement be performed at least annually Anti-Inflammatory Drugs serum FT4 is followed by return of FT4 to normal levels with sustained therapeutic in patients receiving LEVOXYL® (see WARNINGS, PRECAUTIONS, and DOSAGE AND ADMINISTRATION).
serum salicylate concentrations, although total-T4 levels may decrease by as much Salicylates ( > 2 g/day) 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- T Drugs that may alter T4 and T3 metabolism
4. During the first three years of life, the serum total- or free- T4 should be maintained at all times in the upper half of the normal range. While the aim of therapy is to also normalize Drugs that may increase hepatic metabolism, which may result in hypothyroidism
the serum TSH level, this is not always possible in a small percentage of patients, particularly in the first few months Stimulation of hepatic microsomal drug-metabolizing enzyme activity may cause of therapy. TSH may not normalize due to a resetting of the pituitary-thyroid feedback threshold as a result of in utero increased hepatic degradation of levothyroxine, resulting in increased levothyroxine hypothyroidism. Failure of the serum T4 to increase into the upper half of the normal range within 2 weeks of initiation of requirements. Phenytoin and carbamazepine reduce serum protein binding of LEVOXYL® therapy and/or of the serum TSH to decrease below 20 mU/L within 4 weeks should alert the physician to the possibility that the child is not receiving adequate therapy. Careful inquiry should then be made regarding compliance, levothyroxine, and total- and free-T4 may be reduced by 20% to 40%, but most dose of medication administered, and method of administration prior to raising the dose of LEVOXYL®.
patients have normal serum TSH levels and are clinically euthyroid.
Drugs that may decrease T
The recommended frequency of monitoring of TSH and total or free T 4 5'-deiodinase activity
4 in children is as follows: at 2 and 4 weeks after the initiation of treatment; every 1—2 months during the first year of life; every 2—3 months between 1 and 3 years Administration of these enzyme inhibitors decreases the peripheral conversion of T4 of age; and every 3 to 12 months thereafter until growth is completed. More frequent intervals of monitoring may be to T3, leading to decreased T3 levels. However, serum T4 levels are usually normal necessary if poor compliance is suspected or abnormal values are obtained. It is recommended that TSH and T4 levels, - (e.g., Propranolol but may occasionally be slightly increased. In patients treated with large doses and a physical examination, if indicated, be performed 2 weeks after any change in LEVOXYL® dosage. Routine clinical > 160 mg/day) of propranolol (>160 mg/day), T3 and T4 levels change slightly, TSH levels remain examination, including assessment of mental and physical growth and development, and bone maturation, should be normal, and patients are clinically euthyroid. It should be noted that actions of performed at regular intervals (see PRECAUTIONS, Pediatric Use and DOSAGE AND ADMINISTRATION).
- (e.g., Dexamethasone particular beta-adrenergic antagonists may be impaired when the hypothyroid Secondary (pituitary) and tertiary (hypothalamic) hypothyroidism patient is converted to the euthyroid state. Short-term administration of large doses Propylthiouracil (PTU) of glucocorticoids may decrease serum T Adequacy of therapy should be assessed by measuring serum free-T 3 concentrations by 30% with minimal 4 levels, which should be maintained in the upper change in serum T half of the normal range in these patients.
4 levels. However, long-term glucocorticoid therapy may result in slightly decreased T3 and T4 levels due to decreased TBG production (see above).
Many drugs affect thyroid hormone pharmacokinetics and metabolism (e.g., absorption, synthesis, secretion, catabolism, Anticoagulants (oral) Thyroid hormones appear to increase the catabolism of vitamin K-dependent protein binding, and target tissue response) and may alter the therapeutic response to LEVOXYL®. In addition, thyroid - Coumarin Derivatives clotting factors, thereby increasing the anticoagulant activity of oral anticoagulants. hormones and thyroid status have varied effects on the pharmacokinetics and action of other drugs. A listing of - Indandione Derivatives drug-thyroidal axis interactions is contained in Table 2.
Concomitant use of these agents impairs the compensatory increases in clotting factor synthesis. Prothrombin time should be carefully monitored in patients taking The list of drug-thyroidal axis interactions in Table 2 may not be comprehensive due to the introduction of new drugs levothyroxine and oral anticoagulants and the dose of anticoagulant therapy 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.
Concurrent use of tri/tetracyclic antidepressants and levothyroxine may increase the - Tricyclics (e.g., Amitriptyline) therapeutic and toxic effects of both drugs, possibly due to increased receptor Table 2: Drug — Thyroidal Axis Interactions
- Tetracyclics (e.g., Maprotiline) sensitivity to catecholamines. Toxic effects may include increased risk of cardiac - Selective Serotonin Reuptake Drug or Drug Class
arrhythmias and CNS stimulation; onset of action of tricyclics may be accelerated. Administration of sertraline in patients stabilized on levothyroxine may result in Drugs that may reduce TSH secretion -the reduction is not sustained; therefore,
(SSRIs; e.g., Sertraline) increased levothyroxine requirements.
hypothyroidism does not occur
Antidiabetic Agents Addition of levothyroxine to antidiabetic or insulin therapy may result in increased Dopamine / Dopamine Use of these agents may result in a transient reduction in TSH secretion when antidiabetic agent or insulin requirements. Careful monitoring of diabetic control is Agonists Glucocorticoids administered at the following doses: Dopamine (≥1mcg/kg/min); Glucocorticoids recommended, especially when thyroid therapy is started, changed, or discontinued. (hydrocortisone ≥100 mg/day or equivalent); Octreotide (>100 mcg/day).
Drugs that alter thyroid hormone secretion
- Thiazolidediones- Insulin Drugs that may decrease thyroid hormone secretion, which may result in hypothyroidism
Cardiac Glycosides Serum digitalis glycoside levels may be reduced in hyperthyroidism or when Long-term lithium therapy can result in goiter in up to 50% of patients, and either the hypothyroid patient is converted to the euthyroid state. Therapeutic effect of subclinical or overt hypothyroidism, each in up to 20% of patients. The fetus, digitalis glycosides may be reduced.
Iodide (including iodine- neonate, elderly and euthyroid patients with underlying thyroid disease (e.g., containing Radiographic Hashimoto's thyroiditis or with Grave's disease previously treated with radioiodine Therapy with interferon-α has been associated with the development of antithyroid contrast agents) or surgery) are among those individuals who are particularly susceptible to iodine- microsomal antibodies in 20% of patients and some have transient hypothyroidism, induced hypothyroidism. Oral cholecystographic agents and amiodarone are slowly hyperthyroidism, or both. Patients who have antithyroid antibodies before treatment excreted, producing more prolonged hypothyroidism than parenterally administered are at higher risk for thyroid dysfunction during treatment. Interleukin-2 has been Propylthiouracil (PTU) iodinated contrast agents. Long-term aminoglutethimide therapy may minimally associated with transient painless thyroiditis in 20% of patients. Interferon-β γ have not been reported to cause thyroid dysfunction.
4 and T3 levels and increase TSH, although all values remain within normal limits in most patients.
Excessive use of thyroid hormones with growth hormones may accelerate epiphyseal closure. However, untreated hypothyroidism may interfere with growth Drugs that may increase thyroid hormone secretion, which may result in hyperthyroidism
response to growth hormone.
Iodide and drugs that contain pharmacologic amounts of iodide may cause Concurrent use may produce marked hypertension and tachycardia; cautious Iodide (including iodine- hyperthyroidism in euthyroid patients with Grave's disease previously treated with administration to patients receiving thyroid hormone therapy is recommended.
containing Radiographic antithyroid drugs or in euthyroid patients with thyroid autonomy (e.g., multinodular contrast agents) goiter or hyperfunctioning thyroid adenoma). Hyperthyroidism may develop over Decreased theophylline clearance may occur in hypothyroid patients; clearance several weeks and may persist for several months after therapy discontinuation. returns to normal when the euthyroid state is achieved.
Amiodarone may induce hyperthyroidism by causing thyroiditis.
- (e.g., Theophylline) Table 2: Drug — Thyroidal Axis Interactions (cont'd)
During the first 2 weeks of LEVOXYL® therapy, infants should be closely monitored for cardiac overload, arrhythmias, and aspiration from avid suckling.
Drug or Drug Class
The patient should be monitored closely to avoid undertreatment or overtreatment. Undertreatment may have deleterious Radiographic Agents Thyroid hormones may reduce the uptake of 123I, 131I, and 99mTc.
effects on intellectual development and linear growth. Overtreatment has been associated with craniosynostosis in Concurrent use may increase the effects of sympathomimetics or thyroid hormone. infants, and may adversely affect the tempo of brain maturation and accelerate the bone age with resultant premature Thyroid hormones may increase the risk of coronary insufficiency when closure of the epiphyses and compromised adult stature.
sympathomimetic agents are administered to patients with coronary artery disease.
Acquired Hypothyroidism in Pediatric Patients These agents have been associated with thyroid hormone and / or TSH level The patient should be monitored closely to avoid undertreatment and overtreatment. Undertreatment may result in poor alterations by various mechanisms.
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 Because of the increased prevalence of cardiovascular disease among the elderly, levothyroxine therapy should not be Resorcinol (excessive initiated at the full replacement dose (see WARNINGS, PRECAUTIONS, and DOSAGE AND ADMINISTRATION).
topical use)Thiazide Diuretics Oral anticoagulants — Levothyroxine increases the response to oral anticoagulant therapy. Therefore, a decrease in Adverse reactions associated with levothyroxine therapy are primarily those of hyperthyroidism due to therapeutic the dose of anticoagulant may be warranted with correction of the hypothyroid state or when the LEVOXYL® dose is overdosage. They include the following: increased. Prothrombin time should be closely monitored to permit appropriate and timely dosage adjustments (see General: fatigue, increased appetite, weight loss, heat intolerance, fever, excessive sweating;
Table 2).
Central nervous system: headache, hyperactivity, nervousness, anxiety, irritability, emotional lability, insomnia;
Digitalis glycosides — The therapeutic effects of digitalis glycosides may be reduced by levothyroxine. Serum digitalis Musculoskeletal: tremors, muscle weakness;
glycoside levels may be decreased when a hypothyroid patient becomes euthyroid, necessitating an increase in the Cardiac: palpitations, tachycardia, arrhythmias, increased pulse and blood pressure, heart failure, angina, myocardial
dose of digitalis glycosides (see Table 2).
infarction, cardiac arrest; Consumption of certain foods may affect levothyroxine absorption thereby necessitating adjustments in dosing. GI: diarrhea, vomiting, abdominal cramps;
Soybean flour (infant formula), cotton seed meal, walnuts, and dietary fiber may bind and decrease the absorption of Dermatologic: hair loss, flushing;
levothyroxine sodium from the GI tract.
Reproductive: menstrual irregularities, impaired fertility.
Drug-Laboratory Test Interactions
Pseudotumor cerebri and slipped capital femoral epiphysis have been reported in children receiving levothyroxine Changes in TBG concentration must be considered when interpreting T4 and T3 values, which necessitates measurement therapy. Overtreatment may result in craniosynostosis in infants and premature closure of the epiphyses in children and evaluation of unbound (free) hormone and/or determination of the free T4 index (FT4I). Pregnancy, infectious hepatitis, with resultant compromised adult height.
estrogens, estrogen-containing oral contraceptives, and acute intermittent porphyria increase TBG concentrations. Seizures have been reported rarely with the institution of levothyroxine therapy.
Decreases in TBG concentrations are observed in nephrosis, severe hypoproteinemia, severe liver disease, acromegaly,
and after androgen or corticosteroid therapy (see also Table 2). Familial hyper- or hypo-thyroxine binding globulinemias
Inadequate levothyroxine dosage will produce or fail to ameliorate the signs and symptoms of hypothyroidism.
have been described, with the incidence of TBG deficiency approximating 1 in 9000.
Hypersensitivity reactions to inactive ingredients have occurred in patients treated with thyroid hormone products. Carcinogenesis, Mutagenesis, and Impairment of Fertility
These include urticaria, pruritus, skin rash, flushing, angioedema, various GI symptoms (abdominal pain, nausea, Animal studies have not been performed to evaluate the carcinogenic potential, mutagenic potential or effects on vomiting and diarrhea), fever, arthralgia, serum sickness and wheezing. Hypersensitivity to levothyroxine itself is not fertility of levothyroxine. The synthetic T known to occur.
4 in LEVOXYL® is identical to that produced naturally by the human thyroid gland. Although there has been a reported association between prolonged thyroid hormone therapy and breast cancer, In addition to the above events, the following have been reported, predominately when Levoxyl® tablets were not taken this has not been confirmed. Patients receiving LEVOXYL® for appropriate clinical indications should be titrated to the with water: choking, gagging, tablet stuck in throat and dysphagia (see Information for Patients).
lowest effective replacement dose.
Pregnancy — Category A
The signs and symptoms of overdosage are those of hyperthyroidism (see PRECAUTIONS and ADVERSE REACTIONS).
Studies in women taking levothyroxine sodium during pregnancy have not shown an increased risk of congenital In addition, confusion and disorientation may occur. Cerebral embolism, shock, coma, and death have been reported. abnormalities. Therefore, the possibility of fetal harm appears remote. LEVOXYL® should not be discontinued during Seizures have occurred in a child ingesting approximately 20 mg of levothyroxine. Symptoms may not necessarily be pregnancy and hypothyroidism diagnosed during pregnancy should be promptly treated.
evident or may not appear until several days after ingestion of levothyroxine sodium.
Hypothyroidism during pregnancy is associated with a higher rate of complications, including spontaneous abortion, Treatment of Overdosage
pre-eclampsia, stillbirth and premature delivery. Maternal hypothyroidism may have an adverse effect on fetal and Levothyroxine sodium should be reduced in dose or temporarily discontinued if signs or symptoms of overdosage occur.
childhood growth and development. During pregnancy, serum T4 levels may decrease and serum TSH levels increase Acute Massive Overdosage — This may be a life-threatening emergency, therefore, symptomatic and
to values outside the normal range. Since elevations in serum TSH may occur as early as 4 weeks gestation, pregnant supportive therapy should be instituted immediately. If not contraindicated (e.g., by seizures, coma, or loss women taking LEVOXYL® should have their TSH measured during each trimester. An elevated serum TSH level should of the gag reflex), the stomach should be emptied by emesis or gastric lavage to decrease gastrointestinal be corrected by an increase in the dose of LEVOXYL®. Since postpartum TSH levels are similar to preconception values, absorption. Activated charcoal or cholestyramine may also be used to decrease absorption. Central and the LEVOXYL® dosage should return to the pre-pregnancy dose immediately after delivery. A serum TSH level should be peripheral increased sympathetic activity may be treated by administering B-receptor antagonists, e.g., obtained 6—8 weeks postpartum.
propranolol (1 to 3 mg intravenously over a 10-minute period, or orally, 80 to 160 mg/day). Provide respiratory Thyroid hormones do not readily cross the placental barrier; however, some transfer does occur as evidenced by levels support as needed; control congestive heart failure; control fever, hypoglycemia, and fluid loss as necessary. in cord blood of athyreotic fetuses being approximately one-third maternal levels. Transfer of thyroid hormone from the Glucocorticoids may be given to inhibit the conversion of T4 to T3. Because T4 is highly protein bound, very little mother to the fetus, however, may not be adequate to prevent in utero hypothyroidism.
drug will be removed by dialysis.
DOSAGE AND ADMINISTRATION
Although thyroid hormones are excreted only minimally in human milk, caution should be exercised when LEVOXYL® is administered to a nursing woman. However, adequate replacement doses of levothyroxine are generally needed to The goal of replacement therapy is to achieve and maintain a clinical and biochemical euthyroid state. The goal of maintain normal lactation.
suppressive therapy is to inhibit growth and/or function of abnormal thyroid tissue. The dose of LEVOXYL® that is adequate to achieve these goals depends on a variety of factors including the patient's age, body weight, cardiovascular status, concomitant medical conditions, including pregnancy, concomitant medications, and the specific nature of the The goal of treatment in pediatric patients with hypothyroidism is to achieve and maintain normal intellectual and condition being treated (see WARNINGS and PRECAUTIONS). Hence, the following recommendations serve only as
physical growth and development.
dosing guidelines. Dosing must be individualized and adjustments made based on periodic assessment of the patient's
clinical response and laboratory parameters (see PRECAUTIONS, Laboratory Tests).
The initial dose of levothyroxine varies with age and body weight (see DOSAGE AND ADMINISTRATION, Table 3).
Dosing adjustments are based on an assessment of the individual patient's clinical and laboratory parameters (see
The LEVOXYL® should be taken in the morning on an empty stomach, at least one-half hour before any food is eaten. PRECAUTIONS, Laboratory Tests).
LEVOXYL® should be taken at least 4 hours apart from drugs that are known to interfere with its absorption (see
PRECAUTIONS, Drug Interactions).
In children in whom a diagnosis of permanent hypothyroidism has not been established, it is recommended that levothyroxine administration be discontinued for a 30-day trial period, but only after the child is at least 3 years of LEVOXYL® should be taken with water (see Information for Patients and ADVERSE REACTIONS).
age. Serum T4 and TSH levels should then be obtained. If the T4 is low and the TSH high, the diagnosis of permanent Due to the long half-life of levothyroxine, the peak therapeutic effect at a given dose of levothyroxine sodium may not hypothyroidism is established, and levothyroxine therapy should be reinstituted. If the T4 and TSH levels are normal, be attained for 4—6 weeks.
euthyroidism may be assumed and, therefore, the hypothyroidism can be considered to have been transient. In this Caution should be exercised when administering LEVOXYL® to patients with underlying cardiovascular disease, to the instance, however, the physician should carefully monitor the child and repeat the thyroid function tests if any signs elderly, and to those with concomitant adrenal insufficiency (see PRECAUTIONS).
or symptoms of hypothyroidism develop. In this setting, the clinician should have a high index of suspicion of relapse. If the results of the levothyroxine withdrawal test are inconclusive, careful follow-up and subsequent testing will be Specific Patient Populations:
Hypothyroidism in Adults and in Children in Whom Growth and Puberty are Complete (see WARNINGS and
PRECAUTIONS, Laboratory Tests) Therapy may begin at full replacement doses in otherwise healthy individuals less
Since some more severely affected children may become clinically hypothyroid when treatment is discontinued for than 50 years old and in those older than 50 years who have been recently treated for hyperthyroidism or who have 30 days, an alternate approach is to reduce the replacement dose of levothyroxine by half during the 30-day trial been hypothyroid for only a short time (such as a few months). The average full replacement dose of levothyroxine period. If, after 30 days, the serum TSH is elevated above 20 mU/L, the diagnosis of permanent hypothyroidism is sodium is approximately 1.7 mcg/kg/day (e.g., 100—125 mcg/day for a 70 kg adult). Older patients may require
confirmed, and ful replacement therapy should be resumed. However, if the serum TSH has not risen to greater than less than 1 mcg/kg/day. Levothyroxine sodium doses greater than 200 mcg/day are seldom required. An inadequate 20mU/L, levothyroxine treatment should be discontinued for another 30-day trial period fol owed by repeat serum response to daily doses ≥300 mcg/day is rare and may indicate poor compliance, malabsorption, and/or drug The presence of concomitant medical conditions should be considered in certain clinical circumstances and, if present, For most patients older than 50 years or for patients under 50 years of age with underlying cardiac disease, an initial appropriately treated (see PRECAUTIONS).
starting dose of 25—50 mcg/day of levothyroxine sodium is recommended, with gradual increments in dose at
Congenital Hypothyroidism (see PRECAUTIONS, Laboratory Tests and DOSAGE AND ADMINISTRATION)
6—8 week intervals, as needed. The recommended starting dose of levothyroxine sodium in elderly patients with Rapid restoration of normal serum T4 concentrations is essential for preventing the adverse effects of congenital cardiac disease is 12.5—25 mcg/day, with gradual dose increments at 4—6 week intervals. The levothyroxine
hypothyroidism on intellectual development as well as on overall physical growth and maturation. Therefore, LEVOXYL® sodium dose is generally adjusted in 12.5—25 mcg increments until the patient with primary hypothyroidism is therapy should be initiated immediately upon diagnosis and is generally continued for life.
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
Pregnancy — Pregnancy may increase levothyroxine requirements (see PREGNANCY).
increases of 25 mcg/day every 2—4 weeks, accompanied by clinical and laboratory assessment, until the TSH level Subclinical Hypothyroidism — If this condition is treated, a lower levothyroxine sodium dose (e.g., 1 mcg/kg/day) than
is normalized.
that used for full replacement may be adequate to normalize the serum TSH level. Patients who are not treated should In patients with secondary (pituitary) or tertiary (hypothalamic) hypothyroidism, the levothyroxine sodium dose should be monitored yearly for changes in clinical status and thyroid laboratory parameters.
be titrated until the patient is clinically euthyroid and the serum free-T4 level is restored to the upper half of the normal 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 Pediatric Dosage — Congenital or Acquired Hypothyroidism (see PRECAUTIONS, Laboratory Tests)
for benign nodular disease is controversial. Therefore, the dose of LEVOXYL® used for TSH suppression should be individualized based on the specific disease and the patient being treated.
In general, levothyroxine therapy should be instituted at full replacement doses as soon as possible. Delays in In the treatment of well differentiated (papillary and follicular) thyroid cancer, levothyroxine is used as an adjunct to diagnosis and institution of therapy may have deleterious effects on the child's intellectual and physical growth and 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.
Undertreatment and overtreatment should be avoided (see PRECAUTIONS, Pediatric Use).
In the treatment of benign nodules and nontoxic multinodular goiter, TSH is generally suppressed to a higher target LEVOXYL® may be administered to infants and children who cannot swallow intact tablets by crushing the tablet and (e.g., 0.1—0.5 mU/L for nodules and 0.5—1.0 mU/L for multinodular goiter) than that used for the treatment of thyroid suspending the freshly crushed tablet in a small amount (5—10 mL or 1—2 teaspoons) of water. This suspension cancer. Levothyroxine sodium is contraindicated if the serum TSH is already suppressed due to the risk of precipitating can be administered by spoon or dropper. DO NOT STORE THE SUSPENSION. Foods that decrease absorption of
overt thyrotoxicosis (see CONTRAINDICATIONS, WARNINGS and PRECAUTIONS).
levothyroxine, such as soybean infant formula, should not be used for administering levothyroxine sodium tablets.
(see PRECAUTIONS, Drug-Food Interactions).
Myxedema Coma — Myxedema coma is a life-threatening emergency characterized by poor circulation and hypometabolism, and may result in unpredictable absorption of levothyroxine sodium from the gastrointestinal tract. Therefore, oral thyroid hormone drug products are not recommended to treat this condition. Thyroid hormone products The recommended starting dose of levothyroxine sodium in newborn infants is 10—15 mcg/kg/day. A lower starting
formulated for intravenous administration should be administered.
dose (e.g., 25 mcg/day) should be considered in infants at risk for cardiac failure, and the dose should be increased in 4—6 weeks as needed based on clinical and laboratory response to treatment. In infants with very low (< 5 mcg/dL) or HOW SUPPLIED
undetectable serum T – LEVOXYL®(levothyroxine sodium tablets, USP) are supplied as oval, color-coded, potency marked tablets in
4 concentrations, the recommended initial starting dose is 50 mcg/day of levothyroxine sodium.
Infants and Children Levothyroxine therapy is usually initiated at full replacement doses, with the recommended dose per body weight Strength (mcg)
NDC # for bottles of 100
NDC # for bottles of 1000
decreasing with age (see TABLE 3). However, in children with chronic or severe hypothyroidism, an initial dose of
25 mcg/day of levothyroxine sodium is recommended with increments of 25 mcg every 2—4 weeks until the desired
NDC 60793-851-01 effect is achieved.
NDC 60793-852-01 Hyperactivity in an older child can be minimized if the starting dose is one-fourth of the recommended full replacement NDC 60793-853-01 dose, and the dose is then increased on a weekly basis by an amount equal to one-fourth the full recommended replacement dose until the full recommended replacement dose is reached.
NDC 60793-854-01 NDC 60793-855-01 Table 3: Levothyroxine Sodium Dosing Guidelines for Pediatric Hypothyroidism
NDC 60793-856-01 Daily Dose Per Kg Body Weight a
NDC 60793-857-01 0—3 months
3—6 months
NDC 60793-858-01 6—12 months
NDC 60793-859-01 1—5 years
NDC 60793-860-01 6—12 years
4—5 mcg/kg/day
>12 years
20°—25°C (68°—77°F) with excursions permitted between 15°—30°C (59°—86°F).
Growth and puberty complete
Meets USP Dissolution Tests 1 and 2.
a - The dose should be adjusted based on clinical response and laboratory parameters (see PRECAUTIONS, Laboratory
Tests and Pediatric Use).
Distributed by: Pfizer Inc
New York, NY 10017 LAB-0709-1.0Revised September 2014

Source: http://www.levoxyl.com/sites/default/themes/levoxyl/pdf/LEVOXYL%20Recognizing%20Your%20Pill%20Tip%20Sheet.pdf