euthyrox

Administer once daily, 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 ) Starting dose depends on a variety of factors, including age, body weight, cardiovascular status, concomitant medical conditions (including pregnancy), concomitant medications, co-administered food, and the specific nature of the condition being treated. Peak therapeutic effect may not be attained for 4 to 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 General Administration Information Administer EUTHYROX tablets orally as a single daily dose, on an empty stomach, one-half to one hour before breakfast. Administer EUTHYROX at least 4 hours before or after drugs known to interfere with EUTHYROX absorption [see Drug Interactions (7.1) ]. Evaluate the need for dose adjustments when regularly administering within one hour of certain foods that may affect EUTHYROX absorption [see Drug Interactions (7.9) , Clinical Pharmacology (12.3) ]. Administer EUTHYROX to infants and children who cannot…

Adverse reactions associated with EUTHYROX therapy are primarily those of hyperthyroidism due to therapeutic overdosage [see Warnings and Precautions (5) , 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, muscular weakness and cramps Cardiovascular: palpitations, tachycardia, arrhythmias, increased pulse and blood pressure, heart failure, angina, myocardial infarction, cardiac arrest Respiratory: dyspnea Gastrointestinal: diarrhea, vomiting, abdominal cramps and 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 levothyroxine therapy. Adverse reactions associated with EUTHYROX 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 Provell Pharmaceuticals, LLC at 1-888-899-7041 or FDA…

EUTHYROX is contraindicated in patients with uncorrected adrenal insufficiency [ see Warnings and Precautions (5.3) ]. Uncorrected adrenal insufficiency. ( 4 )

The signs and symptoms of overdosage are those of hyperthyroidism [See Warnings and Precautions (5.4) and Adverse Reactions (6) ]. In addition, confusion and disorientation may occur. Cerebral embolism, shock, coma, and death have been reported. Seizures occurred in a 3 year-old child ingesting 3.6 mg levothyroxine. Symptoms may not necessarily be evident or may not appear until several days after ingestion of levothyroxine sodium. Reduce the EUTHYROX 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.

U.S. Poison Control: call or text 1-800-222-1222 (free, 24/7). In an emergency call 911. From the FDA label; not medical advice.

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 EUTHYROX. ( 7 ) 7.1 Drugs Known to Affect Thyroid Hormone Pharmacokinetics Many drugs can exert effects on thyroid hormone pharmacokinetics (e.g. absorption, synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to EUTHYROX (see Tables 2 – 5). Table 2: Drugs That May Decrease T4 Absorption (Hypothyroidism) Potential impact: Concurrent use may reduce the efficacy of EUTHYROX by binding and delaying or preventing absorption, potentially resulting in hypothyroidism Drug or Drug Class Effect Calcium Carbonate Ferrous Sulfate Calcium carbonate may form an insoluble chelate with levothyroxine, and ferrous sulfate likely forms a ferric-thyroxine complex. Administer EUTHYROX at least 4 hours apart from these agents. Orlistat Monitor patients treated concomitantly with orlistat and EUTHYROX for changes in thyroid function. Bile Acid Sequestrants -Colesevelam -Cholestyramine -Colestipol Ion Exchange Resins -Kayexalate -Sevelamer Bile acid sequestrants and ion exchange resins are known to decrease levothyroxine absorption. Administer EUTHYROX at least 4 hours prior to these drugs or monitor thyrotropin (TSH) levels. Other drugs: Proton Pump Inhibitors Sucralfate Antacids - 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 3: 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 EUTHYROX 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 increased free-T4 fraction in serum. Furosemide competes for T4-binding sites on TBG, prealbumin, and albumin, so that a single high dose can acutely lower the total T4 level. Phenytoin and carbamazepine reduce serum protein binding of 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 4: 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 EUTHYROX 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 5: 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 the 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 Table 3 above). Other: Amiodarone Amiodarone inhibits peripheral conversion of levothyroxine (T4) to triiodothyronine (T3) and may cause isolated biochemical changes (increase in serum free-T4, and decrease or normal free-T3) in clinically euthyroid patients. 7.2 Antidiabetic Therapy Addition of EUTHYROX 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 EUTHYROX is started, changed, or discontinued [see Warnings and Precautions (5.5) ]. 7.3 Oral Anticoagulants EUTHYROX 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 EUTHYROX dose is increased. Closely monitor coagulation tests to permit appropriate and timely dosage adjustments. 7.4 Digitalis Glycosides EUTHYROX 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 EUTHYROX 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. EUTHYROX may accelerate the onset of action of tricyclics. Administration of sertraline in patients stabilized on EUTHYROX may result in increased EUTHYROX requirements. 7.6 Ketamine Concurrent use of ketamine and EUTHYROX may produce marked hypertension and tachycardia. Closely monitor blood pressure and heart rate in these patients. 7.7 Sympathomimetics Concurrent use of sympathomimetics and EUTHYROX 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 EUTHYROX absorption thereby necessitating adjustments in dosing [see Dosage and Administration (2.1) ]. Soybean flour (infant formula), cottonseed meal, walnuts, and dietary fiber may bind and decrease the absorption of EUTHYROX from the gastrointestinal tract. Grapefruit juice may delay the absorption of levothyroxine and reduce its bioavailability. 7.10 Drug–Laboratory Test Interactions Consider changes in TBG concentration when interpreting T 4 and T 3 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 concentrations. Nephrosis, severe hypoproteinemia, severe liver disease, acromegaly, androgens and corticosteroids decrease TBG concentration. Familial hyper- or hypo-thyroxine binding globulinemias have been described, with the incidence of TBG deficiency approximating 1 in 9000.