Novothyrox Dailymed

Circulating thyroid hormones are greater than 99% bound to plasma proteins, including thyroxine-binding globulin (TBG), thyroxinebinding 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. Proteinbound thyroid hormones exist in reverse equilibrium with small amounts of free hormone. Only unbound hormone is metabolically active. Many drugs and physiologic conditions affect the binding of thyroid hormones to serum proteins (see PRECAUTIONS, Drug Interactions and Drug-Laboratory Test Interactions ). Thyroid hormones do not readily cross the placental barrier (see PRECAUTIONS, Pregnancy ).

Patients should be informed of the following information to aid in the safe and effective use of NOVOTHYROX: 1. Notify 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. 2. Notify 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 NOVOTHYROX. If you have diabetes, monitor your blood and/or urinary glucose levels as directed by your physician and immediately report any changes to your physician. If you are taking anticoagulants (blood thinners), your clotting status should be checked frequently. 3. Use NOVOTHYROX only as prescribed by your physician. Do not discontinue or change the amount you take or how often you take it, unless directed to do so by your physician. 4. The levothyroxine in NOVOTHYROX 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). 5. Take NOVOTHYROX as a single dose, preferably on an empty stomach, one-half to one hour before breakfast. Levothyroxine absorption is increased on an empty stomach. 6. It may take several weeks before you notice an improvement in your symptoms. 7. Notify your physician if you 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. 8. Notify your physician if you become pregnant while taking NOVOTHYROX. It is likely that your dose of NOVOTHYROX will need to be increased while you are pregnant. 9. Notify your physician or dentist that you are taking NOVOTHYROX prior to any surgery. 10. Partial hair loss may occur rarely during the first few months of NOVOTHYROX therapy, but this is usually temporary. 11. NOVOTHYROX should not be used as a primary or adjunctive therapy in a weight control program. 12. Keep NOVOTHYROX out of the reach of children. Store NOVOTHYROX away from heat, moisture, and light. 13. Agents such as iron and calcium supplements and antacids can decrease the absorption of levothyroxine tablets. Therefore, levothyroxine sodium tablets should not be administered within 4 hours of these agents. 14. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

GENERAL The diagnosis of hypothyroidism is confirmed by measuring TSH levels using a sensitive assay (second generation assay sensitivity ≤ 0.1 mIU/L or third generation assay sensitivity ≤ 0.01 mIU/L) and measurement of free-T4. The adequacy of therapy is determined by periodic assessment of appropriate laboratory tests and clinical evaluation. The choice of laboratory tests depends on various factors including the etiology of the underlying thyroid disease, 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 NOVOTHYROX may be evidence of inadequate absorption, poor compliance, drug interactions, or decreased T4 potency of the drug product. ADULTS In adult patients with primary (thyroidal) hypothyroidism, serum TSH levels (using a sensitive assay) alone may be used to monitor therapy. The frequency of TSH monitoring during levothyroxine dose titration depends on the clinical 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 of levothyroxine changed, the serum TSH concentration should be measured after 8-12 weeks. When the optimum replacement dose has been attained, clinical (physical examination) and biochemical monitoring may be performed every 6-12 months, depending on the clinical situation, and whenever there is a change in the patient’s status. It is recommended that a physical examination and a serum TSH measurement be performed at least annually in patients receiving NOVOTHYROX (see WARNINGS, PRECAUTIONS , and DOSAGE AND ADMINISTRATION ). PEDIATRICS In patients with congenital hypothyroidism, the adequacy of replacement therapy should be assessed by measuring both serum TSH (using a sensitive assay) and total- or free-T4. During the first three years of life, the serum total- or free-T4 should be maintained at all times in the upper half of the normal range. While the aim of therapy is to also normalize the serum TSH level, this is not always possible in a small percentage of patients, particularly in the first few months of therapy. TSH may not normalize due to a resetting of the pituitary-thyroid feedback threshold as a result of in utero hypothyroidism. Failure of the serum T4 to increase into the upper half of the normal range within 2 weeks of initiation of NOVOTHYROX 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, dose of medication administered, and method of administration prior to raising the dose of NOVOTHYROX. The recommended frequency of monitoring of TSH and total- or free-T4 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 of age; and every 3 to 12 months thereafter until growth is completed. More frequent intervals of monitoring may be necessary if poor compliance is suspected or abnormal values are obtained. It is recommended that TSH and T4 levels, and a physical examination, if indicated, be performed 2 weeks after any change in NOVOTHYROX dosage. Routine clinical examination, including assessment of mental and physical growth and development, and bone maturation, should be performed at regular intervals (see PRECAUTIONS, Pediatric Use , and DOSAGE AND ADMINISTRATION ). SECONDARY (PITUITARY) AND TERTIARY (HYPOTHALAMIC) HYPOTHYROIDISM Adequacy of therapy should be assessed by measuring serum free-T4 levels, which should be maintained in the upper half of the normal range in these patients.

Changes in TBG concentration must be considered when interpreting T and T values, which necessitates measurement and evaluation of unbound (free) hormone and/or determination of the free-T index (FTI). Pregnancy, infectious hepatitis, estrogens, estrogen-containing oral contraceptives, and acute intermittent porphyria increases TBG concentrations. Decreases in TBG concentrations are observed in nephrosis, severe hypoproteinemia, severe liver disease, acromegaly, and after androgen or corticosteroid therapy (see also ). Familial hyper- or hypo-thyroxine binding globulinemias have been described, with the incidence of TBG deficiency approximating 1 in 9000.

Changes in TBG concentration must be considered when interpreting T4 and T3 values, which necessitates measurement and evaluation of unbound (free) hormone and/or determination of the free-T4 index (FT4I). Pregnancy, infectious hepatitis, estrogens, estrogen-containing oral contraceptives, and acute intermittent porphyria increases TBG concentrations. 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 have been described, with the incidence of TBG deficiency approximating 1 in 9000.

Studies in women taking levothyroxine sodium during pregnancy have not shown an increased risk of congenital abnormalities. Therefore, the possibility of fetal harm appears remote. NOVOTHYROX should not be discontinued during pregnancy and hypothyroidism diagnosed during pregnancy should be promptly treated.

Studies in women taking levothyroxine sodium during pregnancy have not shown an increased risk of congenital abnormalities. Therefore, the possibility of fetal harm appears remote. NOVOTHYROX should not be discontinued during pregnancy and hypothyroidism diagnosed during pregnancy should be promptly treated. Hypothyroidism during pregnancy is associated with a higher rate of complications, including spontaneous abortion, pre-eclampsia, stillbirth and premature delivery. Maternal hypothyroidism may have an adverse effect on fetal and childhood growth and development. During pregnancy, serum T4 levels may decrease and serum TSH levels increase to values outside the normal range. Since elevations in serum TSH may occur as early as 4 weeks gestation, pregnant women taking NOVOTHYROX should have their TSH measured during each trimester. An elevated serum TSH level should be corrected by an increase in the dose of NOVOTHYROX. Since postpartum TSH levels are similar to preconception values, the NOVOTHYROX dosage should return to the pre-pregnancy dose immediately after delivery. A serum TSH level should be obtained 6-8 weeks postpartum. Thyroid hormones cross the placental barrier to some extent as evidenced by levels in cord blood of athyreotic fetuses being approximately one-third maternal levels. Transfer of thyroid hormone from the mother to the fetus, however, may not be adequate to prevent in utero hypothyroidism.

Although thyroid hormones are excreted only minimally in human milk, caution should be exercised when NOVOTHYROX is administered to a nursing woman. However, adequate replacement doses of levothyroxine are generally needed to maintain normal lactation.

The goal of replacement therapy is to achieve and maintain a clinical and biochemical euthyroid state. The goal of suppressive therapy is to inhibit growth and/or function of abnormal thyroid tissue. The dose of NOVOTHYROX that is adequate to achieve these goals depends on a variety of factors including the patient’s age, body weight, cardiovascular status, concomitant medical conditions, including pregnancy, concomitant medications, and the specific nature of the condition being treated (see and ). Hence, the following recommendations serve only as dosing guidelines. Dosing must be individualized and adjustments made based on periodic assessment of the patient’s clinical response and laboratory parameters (see , ).

The goal of replacement therapy is to achieve and maintain a clinical and biochemical euthyroid state. The goal of suppressive therapy is to inhibit growth and/or function of abnormal thyroid tissue. The dose of NOVOTHYROX that is adequate to achieve these goals depends on a variety of factors including the patient’s age, body weight, cardiovascular status, concomitant medical conditions, including pregnancy, concomitant medications, and the specific nature of the condition being treated (see WARNINGS and PRECAUTIONS ). Hence, the following recommendations serve only as dosing guidelines. Dosing must be individualized and adjustments made based on periodic assessment of the patient’s clinical response and laboratory parameters (see PRECAUTIONS , Laboratory Tests ). NOVOTHYROX is administered as a single daily dose, preferably one-half to one hour before breakfast. NOVOTHYROX should be taken at least 4 hours apart from drugs that are known to interfere with its absorption (see PRECAUTIONS , Drug Interactions ). Due to the long half-life of levothyroxine, the peak therapeutic effect at a given dose of levothyroxine sodium may not be attained for 4-6 weeks. Caution should be exercised when administering NOVOTHYROX to patients with underlying cardiovascular disease, to the elderly, and to those with concomitant adrenal insufficiency (see PRECAUTIONS ).

HYPOTHYROIDISM IN ADULTS AND IN CHILDREN IN WHOM GROWTH AND PUBERTY ARE COMPLETE (see WARNINGS and PRECAUTIONS, Laboratory Tests ) Therapy may begin at full replacement doses in otherwise healthy individuals less than 50 years old and in those older than 50 years who have been recently treated for hyperthyroidism or who have been hypothyroid for only a short time (such as a few months). The average full replacement dose of levothyroxine sodium is approximately 1.7 mcg/kg/day (e.g., 100-125 mcg/day for a 70 kg adult). Older patients may require less than 1 mcg/kg/day. Levothyroxine doses greater than 200 mcg/day are seldom required. An inadequate response to daily doses ≥ 300 mcg/day is rare and may indicate poor compliance, malabsorption, and/or drug interactions. For most patients older than 50 years or for patients under 50 years of age with underlying cardiac disease, an initial starting dose of 25-50 mcg/day of levothyroxine sodium is recommended, with gradual increments in dose at 6-8 week intervals, as needed. The recommended starting dose of levothyroxine sodium in elderly patients with cardiac disease is 12.5-25 mcg/day, with gradual dose increments at 4-6 week intervals. The levothyroxine sodium dose is generally adjusted in 12.5-25 mcg increments until the patient with primary hypothyroidism is clinically euthyroid and the serum TSH has normalized. In patients with severe hypothyroidism, the recommended initial levothyroxine sodium dose is 12.5-25 mcg/day with increases of 25 mcg/day every 2-4 weeks, accompanied by clinical and laboratory assessment, until the TSH level is normalized. In patients with secondary (pituitary) or tertiary (hypothalamic) hypothyroidism, the levothyroxine sodium dose should be titrated until the patient is clinically euthyroid and the serum free-T4 level is restored to the upper half of the normal range. PEDIATRIC DOSAGE – CONGENITAL OR ACQUIRED HYPOTHYROIDISM (see PRECAUTIONS , Laboratory Tests ) General Principles In general, levothyroxine therapy should be instituted at full replacement doses as soon as possible. Delays in diagnosis and institution of therapy may have deleterious effects on the child’s intellectual and physical growth and development. Undertreatment and overtreatment should be avoided (see PRECAUTIONS , Pediatric Use ). NOVOTHYROX may be administered to infants and children who cannot swallow intact tablets by crushing the tablet and suspending the freshly crushed tablet in a small amount (5-10 mL or 1-2 teaspoons) of water. This suspension can be administered by spoon or dropper. DO NOT STORE THE SUSPENSION. Foods that decrease absorption of levothyroxine, such as soybean infant formula, should not be used for administering levothyroxine sodium tablets (see PRECAUTIONS , Drug-Food Interactions ). Newborns The recommended starting dose of levothyroxine sodium in newborn infants is 10-15 mcg/kg/day. A lower starting dose (e.g., 25 mcg/day) should be considered in infants at risk for cardiac failure, and the dose should be increased in 4-6 weeks as needed based on clinical and laboratory response to treatment. In infants with very low (< 5 mcg/dL) or undetectable serum T4 concentrations, the recommended initial starting dose is 50 mcg/day of levothyroxine sodium. Infants and Children Levothyroxine therapy is usually initiated at full replacement doses, with the recommended dose per body weight decreasing with age (see Table 3). However, in children with chronic or severe hypothyroidism, an initial dose of 25 mcg/day of levothyroxine sodium is recommended with increments of 25 mcg every 2-4 weeks until the desired effect is achieved. Hyperactivity in an older child can be minimized if the starting dose is one-fourth of the recommended full replacement dose, and the dose is then increased on a weekly basis by an amount equal to one-fourth the full-recommended replacement dose until the full recommended replacement dose is reached. Table 3: Levothyroxine Dosing Guidelines for Pediatric Hypothyroidism AGE Daily Dose Per Kg Body Weighta 0-3 months 10-15 mcg/kg/day 3-6 months 8-10 mcg/kg/day 6-12 months 6-8 mcg/kg/day 1-5 years 5-6 mcg/kg/day 6-12 years 4-5 mcg/kg/day > 12 years but growth and puberty incomplete 2-3 mcg/kg/day Growth and puberty complete 1.7 mcg/kg/day a The dose should be adjusted based on clinical response and laboratory parameters (see PRECAUTIONS, Laboratory Tests and Pediatric Use). Pregnancy Pregnancy may increase levothyroxine requirements (see Pregnancy). Subclinical Hypothyroidism If this condition is treated, a lower levothyroxine sodium dose (e.g., 1 mcg/kg/day) than that used for full replacement may be adequate to normalize the serum TSH level. Patients who are not treated should be monitored yearly for changes in clinical status and thyroid laboratory parameters. TSH Suppression in Well-differentiated Thyroid Cancer and Thyroid Nodules The target level for TSH suppression in these conditions has not been established with controlled studies. In addition, the efficacy of TSH suppression for benign nodular disease is controversial. Therefore, the dose of NOVOTHYROX used for TSH suppression should be individualized based on the specific disease and the patient being treated. In the treatment of well-differentiated (papillary and follicular) thyroid cancer, levothyroxine is used as an adjunct to surgery and radioiodine therapy. Generally, TSH is suppressed to <0.1 mU/L, and this usually requires a levothyroxine sodium dose of greater than 2 mcg/kg/day. However, in patients with high-risk tumors, the target level for TSH suppression may be <0.01 mU/L. In the treatment of benign nodules and nontoxic multinodular goiter, TSH is generally suppressed to a higher target (e.g., 0.1 to either 0.5 or 1.0 mU/L) than that used for the treatment of thyroid cancer. Levothyroxine sodium is contraindicated if the serum TSH is already suppressed due to the risk of precipitating overt thyrotoxicosis (see CONTRAINDICATIONS, WARNINGS and PRECAUTIONS ). 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 drug products formulated for intravenous administration should be administered.