Westhroid

DESCRIPTION

Westhroid™ (ThyroidUSP) Tablets,micro-coated, easy to swallow with a reduced odor, for oral use are natural preparations derived fromporcinethyroid glands (T3 liothyronine is approximately four times as potent as T4levothyroxineon a microgram for microgram basis). They provide 38 mcg levothyroxine (T4) and 9 mcg liothyronine (T3) for each 65 mg (1 Grain) of the labeled content of thyroid.

Inactive Ingredients

ColloidalSiliconDioxide, Dicalcium Phosphate, Lactose Monohydrate*, Magnesium Stearate, Microcrystalline Cellulose, Croscarmellose Sodium, Stearic Acid, Opadry II 85F19316 Clear.

The structural formulas of liothyronine (T3) and levothyroxine (T4) are as follows:

*Present in traceable amount as part of Thyroid USP (diluent)

INDICATIONS

1. As replacement of supplemental therapy in patients withhypothyroidismof anyetiology, except transient hypothyroidism during the recovery phase ofsubacutethyroiditis．This category includescretinism, myxedema, and ordinary hypothyroidism in patients of any age (children, adults, the elderly), or state (including pregnancy); primary hypothyroidism resulting from functional deficiency, primaryatrophy, partial or total absence ofthyroid gland, or the effects of surgery,radiation, or drugs, with or without the presence ofgoiter; and secondary (pituitary), or tertiary (hypothalamic) hypothyroidism (See警告).
2. As pituitary TSH suppressants, in the treatment or prevention of various types ofeuthyroidgoiters, including thyroid nodules, subacute, or chroniclymphocyticthyroiditis (Hashimoto's), multinodular goiter, and in the management ofthyroid cancer．
3. As diagnostic agents in suppression tests to differentiate suspected mild hyperthyroidism or thyroidglandanatomy．

DOSAGE AND ADMINISTRATION

The dosage ofthyroid hormonesis determined by the indication and must in every case be individualized according to patient response and laboratory findings.

Thyroid hormones are given orally. In acute, emergency conditions, injectable levothyroxine sodium (T4) may be given intravenously when oral administration is not feasible or desirable (as in the treatment of myxedema coma, or duringparenteral nutrition).Intramuscularadministration is not advisable because of reported poor absorption.

Hypothyroidism

Therapy is usually instituted using low doses, with increments which depend on thecardiovascularstatus of the patient. The usual starting dose is 32.5 mg, with increment of 16.25 mg every 2 to 3 weeks. A lower starting dosage, 16.25 mg/day, is recommended in patients with longstanding myxedema, particularly if cardiovascular impairment is suspected, in which case extreme caution is recommended. The appearance of心绞痛is an indication for reduction in dosage. Most patients require 65 - 130 mg/day. Failure to respond to doses of 195 mg suggests lack of compliance ormalabsorption．Maintenance dosages 65 - 130 mg/day usually result in normal serum T4 and T3 levels. Adequate therapy usually results in normal TSH and T4 levels after 2 or 3 weeks of therapy.

Readjustment ofthyroid hormonedosage should be made within the first four weeks of therapy, after proper clinical and laboratory evaluations, including serum levels of T4, bound and free, and TSH.

Liothyronine (T3) may be used in preference to levothyroxine (T4) during radio-isotopescanning procedures, since induction of hypothyroidism in those cases is more abrupt and can be of shorter duration. It may also be preferred when impairment of peripheral conversion of levothyroxine (T4) and liothyronine (T3) is suspected.

Myxedema Coma

Myxedema comais usually precipitated in the hypothyroid patient of longstanding by intercurrent illness or drugs such as sedatives and anesthetics and should be considered a medical emergency. Therapy should be directed at the correction ofelectrolytedisturbances and possible infection, besides the administration of thyroid hormones. Corticosteroids should be administered routinely. Levothyroxine (T4) and Liothyronine (T3) may be administered via anasogastric tube, but the preferred route of administration of both hormones is intravenous. Levothyroxine sodium (T4) is given at a starting dose of 400 mcg (100 mcg/mL) given rapidly, and is usually well tolerated, even in the elderly. This initial dose is followed by daily supplements of 100 to 200 mcg given IV. Normal T4 levels are achieved in 24 hours, followed in 3 days by threefold elevation of T3. Oral therapy with thyroid hormone would be resumed as soon as the clinical situation has been stabilized and the patient is able to take oral medication.

Thyroid Cancer

Exogenousthyroid hormone may produce regression of metastases from follicular and papillarycarcinomaof the thyroid and is used as ancillary therapy of these conditions withradioactive iodine．TSH should be suppressed to low or undetectable levels. Therefore, larger amounts of thyroid hormone than those used for replacement therapy are required. Medullary carcinoma of the thyroid is usually unresponsive to this therapy.

Thyroid Suppression Therapy

Administration of thyroid hormone in doses higher than those produced physiologically by the gland results in suppression of the production ofendogenoushormone. This is the basis for the thyroid suppression test and is used as an aid in the diagnosis of patients with signs of mild hyperthyroidism, in whom base line laboratory tests appear normal, or to demonstrate thyroid gland autonomy in patients with Grave'sophthalmopathy．131年我吸收前后的一个决定dministration of the exogenous hormone. A fifty percent or greater suppression of uptake indicates a normal thyroid pituitaryaxis, and thus rules out thyroid gland autonomy.

For adults, the usual suppressive dose of levothyroxine (T4) is 1.56 mg/kg of body weight per day given for 7 to 10 days. These doses usually yield normal serum T4 and T3 levels and lack of response to TSH.

Thyroid hormones should be administered cautiously to patients in whom there is strong suspicion of thyroid gland autonomy, in view of the fact that the exogenous hormone effects will be additive to the endogenous source.

Pediatric Dosage

Pediatric dosage should follow the recommendations summarized in Table 1. In infants withcongenital hypothyroidism, therapy with full doses should be instituted as soon as the diagnosis has been made.

TABLE 1: Recommended Pediatric Dosage for Congenital Hypothyroidism

Age	Dose per day	Daily dose per kg of body weight
0 - 6 months	16.25 - 32.5 mg	4.8-6.0 mg
6 - 12 months	32.5 - 48.75 mg	3.6-4.8 mg
1 - 5 years	48.75 - 65 mg	3.0-3.6 mg
6 - 12 years	65 - 97.5 mg	2.4-3.0 mg
超过12年	Over 97.5 mg	1.2-1.8 mg

HOW SUPPLIED

Westhroid™ (Thyroid USP) Tabletsare supplied as follows:

16.25 mg．(1/4 gr.) in bottles of 30 Count (NDC64727-7065-4), 60 Count (NDC64727-7065-5), 90 Count (NDC64727-7065-6), 100 Count (NDC64727-7065-1), 1,000 Count (NDC64727-7065-2), 990 Count (NDC64727-7065-3) & 1,008 Count (NDC64727-7065-8)

32.5 mg．(½ gr.) in bottles of 30 Count (NDC64727-7070-4), 60 Count (NDC64727-7070-5), 90 Count (NDC64727-7070-6), 100 Count (NDC64727-7070-1), 1,000 Count (NDC64727-7070-2), 990 Count (NDC64727-7070-3) & 1,008 Count (NDC64727-7070-8)

48.75 mg．(3/4 gr.) in bottles of 30 Count (NDC64727-7072-4), 60 Count (NDC64727-7072-5), 90 Count (NDC64727-7072-6), 100 Count (NDC64727-7072-1), 1,000 Count (NDC64727-7072-2), 990 Count (NDC64727-7072-3) & 1,008 Count (NDC64727-7072-8)

65 mg．(1 gr.) in bottles of 30 Count (NDC64727-7073-4), 60 Count (NDC64727-7073-5), 90 Count (NDC64727-7073-6), 100 Count (NDC64727-7073-1), 1,000 Count (NDC64727-7073-2), 990 Count (NDC64727-7073-3) & 1,008 Count (NDC64727-7073-8)

81.25 mg．(1 1/4 gr.) in bottles of 30 Count (NDC64727-7074-4), 60 Count (NDC64727-7074-5), 90 Count (NDC64727-7074-6), 100 Count (NDC64727-7074-1), 1,000 Count (NDC64727-7074-2), 990 Count (NDC64727-7074-3) & 1,008 Count (NDC64727-7074-8)

97.5 mg．(1 ½ gr.) in bottles of 30 Count (NDC64727-7075-4), 60 Count (NDC64727-7075-5), 90 Count (NDC64727-7075-6), 100 Count (NDC64727-7075-1), 1,000 Count (NDC64727-7075-2), 990 Count (NDC64727-7075-3) & 1,008 Count (NDC64727-7075-8)

113.75 mg．(1 3/4 gr.) in bottles of 30 Count (NDC64727-7078-4), 60 Count (NDC64727-7078-5), 90 Count (NDC64727-7078-6), 100 Count (NDC64727-7078-1), 1,000 Count (NDC64727-7078-2), 990 Count (NDC64727-7078-3) & 1,008 Count (NDC64727-7078-8)

130 mg．(2 gr.) in bottles of 30 Count (NDC64727-7080-4), 60 Count (NDC64727-7080-5), 90 Count (NDC64727-7080-6), 100 Count (NDC64727-7080-1), 1,000 Count (NDC64727-7080-2), 990 Count (NDC64727-7080-3) & 1,008 Count (NDC64727-7080-8)

146.25 mg．(2 1/4 gr.) in bottles of 30 Count (NDC64727-7085-4), 60 Count (NDC64727-7085-5), 90 Count (NDC64727-7085-6), 100 Count (NDC64727-7085-1), 1,000 Count (NDC64727-7085-2), 990 Count (NDC64727-7085-3) & 1,008 Count (NDC64727-7085-8)

162.5 mg．(2 ½ gr.) in bottles of 30 Count (NDC64727-7090-4), 60 Count (NDC64727-7090-5), 90 Count (NDC64727-7090-6), 100 Count (NDC64727-7090-1), 1,000 Count (NDC64727-7090-2), 990 Count (NDC64727-7090-3) & 1,008 Count (NDC64727-7090-8)

195 mg．(3 gr.) in bottles of 30 Count (NDC64727-7095-4), 60 Count (NDC64727-7095-5), 90 Count (NDC64727-7095-6), 100 Count (NDC64727-7095-1), 1,000 Count (NDC64727-7095-2), 990 Count (NDC64727-7095-3) & 1,008 Count (NDC64727-7095-8)

260 mg．(4 gr.) in bottles of 30 Count (NDC64727-7100-4), 60 Count (NDC64727-7100-5), 90 Count (NDC64727-7100-6), 100 Count (NDC64727-7100-1), 1,000 Count (NDC64727-7100-2), 990 Count (NDC64727-7100-3) & 1,008 Count (NDC64727-7100-8)

325 mg．(5 gr.) in bottles of 30 Count (NDC64727-7150-4), 60 Count (NDC64727-7150-5), 90 Count (NDC64727-7150-6), 100 Count (NDC64727-7150-1), 1,000 Count (NDC64727-7150-2), 990 Count (NDC64727-7150-3) & 1,008 Count (NDC64727-7150-8)

Storage

Store at controlled room temperature; 15°-30°C (59°-86°F)

Dispense in tight, light-resistant containers as defined in the USP/NF

Distributed by: RLC Labs, Cave Creek, AZ 85331.

SIDE EFFECTS

Adverse reactions other than those indicative of hyperthyroidism because of therapeutic overdosage, either initially or during the maintenance period, are rare (SeeOVERDOSAGE).

DRUG INTERACTIONS

Oral Anticoagulants-Thyroid hormones appear to increasecatabolismofvitamin K- dependent clotting factors. If oral anticoagulants are also being given, compensatory increases in clotting factor synthesis are impaired. Patients stabilized on oral anticoagulants that are found to require thyroid replacement therapy should be watched very closely when thyroid is started. If a patient is truly hypothyroid, it is likely that a reduction inanticoagulantdosage will be required. No special precautions appear to be necessary when oral anticoagulant therapy is begun in a patient already stabilized on maintenance thyroid replacement therapy.

Insulinor OralHypoglycemic-Initiating thyroid replacement therapy may cause increases in insulin or oral hypoglycemic requirements. The effects seen are poorly understood and depend upon a variety of factors such as dose and type of thyroid preparations and endocrine status of the patient. Patients receiving insulin or oral hypoglycemic should be closely watched during initiation of thyroid replacement therapy.

Cholestyramine or Colestipol- Cholestyramine or Colestipol binds both levothyroxine (T4) and liothyronine (T3) in the intestine, thus impairing absorption of these thyroid hormones. In vitro studies indicate that the binding is not easily removed. Therefore, four to five hours should elapse between administration of Cholestyramine or Colestipol and thyroid hormones.

Estrogen, Oral Contraceptives-Estrogenstend to increase serumthyroxine-binding globulin (TBg). In a patient with a nonfunctioning thyroid gland who is receiving thyroid replacement therapy, free levothyroxine (T4) may be decreased when estrogens are started thus increasing thyroid requirements. However, if the patient's thyroid gland has sufficient function, the decreased free levothyroxine (T4) will result in a compensatory increase in levothyroxine (T4) output by the thyroid. Therefore, patients without a functioning thyroid gland who are on thyroid replacement therapy, may need to increase their thyroid dose if estrogens or estrogen-containing oral contraceptives are given.

Drug/Laboratory Test Interactions

The following drugs or moieties are known to interfere with laboratory tests performed in patients on thyroidhormone therapy: androgens, corticosteroids, estrogens, oral contraceptives containing estrogens,iodine-containing preparations, and the numerous preparations containing salicylates.

1. Changes in TBg concentration should be taken into consideration in the interpretation of levothyroxine (T4) and liothyronine (T3) values. In such cases, the unbound (free) hormone should be measured. Pregnancy, estrogens, and estrogen-containing oral contraceptives increase TBg concentrations. TBg may also be increased duringinfectious hepatitis．Decreases in TBg concentrations are observed innephrosis,acromegaly, and afterandrogenorcorticosteroidtherapy.Familialhyper or hypothyroxine-bindingglobulinemias have been described. The incidence of TBg deficiency approximates 1 in 9,000. The binding of levothyroxine by TBPA is inhibited by salicylates.
2. Medicinal or dietary iodine interferes with all in vivo tests of radio-iodine uptake, producing low uptakes which may not be relative of a true decrease in hormone synthesis.
3. The persistence of clinical and laboratory evidence of hypothyroidism in spite of adequate dosage replacement indicates; either poor patient compliance, poor absorption, excessive fecal loss, or inactivity of the preparation. Intracellular resistance to thyroid hormone is quite rare.

警告

Drugs with thyroid hormone activity, alone or together with other therapeutic agents, have been used for the treatment ofobesity．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 theiranorecticeffects.

The use of thyroid hormones in the therapy of obesity, alone or combined with other drugs, is unjustified and has been shown to be ineffective. Neither is their use justified for the treatment of male or femaleinfertilityunless this condition is accompanied by hypothyroidism.

PRECAUTIONS

General

Thyroid hormones should be used with great caution in a number of circumstances where the integrity of thecardiovascular system, particularly thecoronary arteries, is suspected. These include patients with心绞痛pectorisor the elderly, whom have a greater likelihood ofoccultcardiac disease. With these patients, therapy should be initiated with low doses, i.e. 16.25 - 32.5 mg. When, in such patients, a euthyroid state can only be reached at the expense of an aggravation of thecardiovascular disease, thyroid hormone dosage should be reduced.

Thyroid hormone therapy in patients with concomitantdiabetes mellitusordiabetes insipidusor adrenalcorticalinsufficiency aggravates the intensity of their symptoms. Appropriate adjustments of the various therapeutic measures directed at these concomitant endocrine diseases are required. The therapy of myxedema coma requires simultaneous administration of glucorticoids (SeeDOSAGE AND ADMINISTRATION).

Hypothyroidism decreases and hyperthyroidism increases the sensitivity to oral anticoagulants.Prothrombin timeshould be closely monitored in thyroid treated patients on oral anticoagulants and dosage of the latter agents should be adjusted on the basis of frequent凝血酶原time determinations. In infants, excessive doses of thyroid hormone preparations may producecraniosynostosis．

Laboratory Tests

治疗甲状腺激素患者的要求es the periodic assessment of thyroid status by means of appropriate laboratory tests, besides the full clinical evaluation. The TSH suppression test can be used to test the effectiveness of any thyroid preparation, bearing in mind the relative insensitivity of the infant pituitary to the negative feedback effect of thyroid hormones. Serum T4 levels can be used to test the effectiveness of all thyroid medications except T3. When the total serum T4 is low but TSH is normal, a test specific to assess unbound (free) T4 levels is warranted. Specific measurements of T4 and T3 by competitive protein binding orradioimmunoassayare not influenced by blood levels of organic or inorganic iodine.

Carcinogenesis, Mutagenesis, and Impairment of Fertility

A reportedly apparent association between prolonged thyroid therapy andbreast cancerhas not been confirmed and patients on thyroid for established indications should not discontinue therapy. No confirmatory long-term studies in animals have been performed to evaluatecarcinogenicpotential, mutagenicity, or impairment of fertility in either males or females.

Pregnancy-Category A

Thyroid hormones do not readily cross the placental barrier. The clinical experience to date does not indicate anyadverse effecton fetuses when thyroid hormones are administered to pregnant women. On the basis of current knowledge, thyroid replacement therapy to hypothyroid women should not be discontinued during pregnancy.

Nursing Mothers

Minimal amounts of thyroid hormones are excreted in human milk. Thyroid is not associated with serious adverse reactions and does not have a known tumorigenic potential. However, caution should be exercised when thyroid is administered to a nursing woman.

Pediatric Use

Pregnant mothers provide little or no thyroid hormone to the fetus. The incidence ofcongenitalhypothyroidism is relatively high (1:4,000) and the hypothyroid fetus would not derive any benefit from the small amounts of hormone crossing the placental barrier. Routine determination of serumT4 and/or TSH is strongly advised in neonates in view of the deleterious effects of thyroid deficiency on growth and development. Treatment should be initiated immediately upon diagnosis, and maintained for life, unless transient hypothyroidism is suspected; in which case, therapy may be interrupted for 2 to 8 weeks after the age of 3 years to reassess the condition. Cessation of therapy is justified in patients who have maintained a normal TSH during those 2 to 8 weeks.

Geriatric use

Clinical studies of Thyroid Tablets, USP did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

OVERDOSE

Signs and Symptoms

Excessive doses of thyroid result in a hypermetabolic state resembling in every respect the condition of endogenous origin. The condition may be self induced.

过剂量的治疗

Dosage should be reduced or therapy temporarily discontinued signs and symptoms of overdosage appear.

Treatment may be reinstituted at a lower dosage. In normal individuals, normal hypothalamic-pituitarythyroid axis function is restored in 6 to 8 weeks after thyroid suppression.

Treatment of acute massive thyroid hormone overdosage is aimed at reducinggastrointestinalabsorption of the drugs and counteracting central and peripheral effects, mainly those of increased sympathetic activity. Vomiting may be induced initially if further gastrointestinal absorption can reasonably be prevented and barring contraindications such as coma, convulsions, or loss of the gagging reflex. Treatment is symptomatic and supportive. Oxygen may be administered andventilationmaintained. Cardiac glycosides may be indicated ifcongestive heart failuredevelops. Measures to control fever,hypoglycemia, or fluid loss should be instituted if needed. Antiadrenergic agents, particularly propranolol, have been used advantageously in the treatment of increased sympathetic activity. Propranolol may be administered intravenously at a dosage of 1 to 3 mg, over a 10 minute period or orally, 80 to 160 mg/day, initially, especially when no contraindications exist for its use.

CONTRAINDICATIONS

Thyroid hormone preparations are generally contraindicated in patients with diagnosed, but as yet, uncorrected adrenal cortical insufficiency, untreated thyrotoxicosis, and apparent hypersensitivity to any of their active or extraneous constituents. There is no well documented evidence in the literature of true allergic or idiosyncratic reactions to thyroid hormone.

CLINICAL PHARMACOLOGY

The steps in the synthesis of the thyroid hormones are controlled bythyrotropin(Thyroid Stimulating Hormone, TSH) secreted by theanterior pituitary．This hormone's secretion is in turn controlled by a feedback mechanism affected by the thyroid hormones themselves and by thyrotropin releasing hormone (TRH), atripeptideof hypothalamic origin. Endogenous thyroid hormone secretion is suppressed when exogenous thyroid hormones are administered to euthyroid individuals in excess of the normal gland's secretion.

The mechanisms by which thyroid hormones exert theirphysiologicaction are not well understood. These hormones enhance oxygen consumption by most tissues of the body, increase thebasal metabolic rate, and themetabolismofcarbohydrates,lipids, and proteins. Thus, they exert a profound influence on every organ system in the body and are of particular importance in the development of thecentral nervous system．

The normal thyroid gland contains approximately 200 mcg of levothyroxine (T4) per克of gland, and 15 mcg of liothyronine (T3) per gram. The ratio of these two hormones in thecirculationdoes not represent the ratio in the thyroid gland, since about 80 percent of peripheral liothyronine (T3) comes from monodeiodination of levothyroxine (T4). Peripheral monodeiodination of levothyroxine (T4) at the 5 position (inner ring) also results in the formation of reverse liothyronine (T3), which is calorigenically inactive. Liothyronine (T3) levels are low in the fetus and newborn, in old age, in chronic caloric deprivation, hepaticcirrhosis、肾功能衰竭、手术stress, and chronic illnesses representing what has been called the “T3 thyronine syndrome”.

Pharmacokinetics

Animal studies have shown that levothyroxine (T4) is only partially absorbed from thegastrointestinal tract．The degree of absorption is dependent on the vehicle used for its administration and by the character of the intestinal contents, the intestinalflora,包括血浆蛋白和可溶性膳食ctors, all of which bind thyroid, thereby making it unavailable for diffusion. Only 41 percent is absorbed when given in agelatincapsule, as opposed to 74 percent absorption when given with analbumincarrier.

Depending on other factors, absorption has varied from 48 to 79 percent of the administered dose. Fasting increases absorption. Malabsorption syndromes, as well as dietary factors, (children's soybean formula, concomitant use of anionic exchange resins such as cholestyramine) cause excessive fecal loss. Liothyronine (T3) is almost totally absorbed, 95 percent in 4 hours. The hormones contained in the natural preparations are absorbed in a manner similar to the synthetic hormones.

More than 99 percent of circulating hormones are bound to serum proteins, including thyroid-binding globulin (TBg), thyroid-binding pre-albumin (TBPA), and albumin (TBa), whose capacities and affinities vary for the hormones. The higheraffinityof levothyroxine (T4) for both TBg and TBPA, as compared to liothyronine (T3), partially explains the higher serum levels and longer half-life of the former hormone. Both protein-bound hormones exist in reverse equilibrium with minute amounts of free hormone, the latter accounting for the metabolic activity. Deiodination of levothyroxine (T4) occurs at a number of sites, including liver, kidney, and other tissues. The conjugated hormone, in the form of glucuronide or sulfate, is found in thebileand gut where it may complete an enterohepatic circulation. Eighty-five percent of levothyroxine (T4) metabolized daily is deiodinated.

PATIENT INFORMATION

Patients on thyroid hormone preparations and parents of children on thyroid therapy should be informed that:

1. Replacement therapy is to be taken essentially for life, with the exception of cases of transient hypothyroidism, usually associated with thyroiditis, and in those patients receiving a therapeutic trial of the drug.
2. They should immediately report, during the course of therapy, any signs or symptoms of thyroid hormone toxicity, e.g., chest pain, increasedpulserate,palpitations过度出汗,intoler热ance, nervousness, or any other unusual event.
3. In case of concomitantdiabetesmellitus, the daily dosage of antidiabetic medication may need readjustment as thyroid hormone replacement is achieved. If thyroid medication is stopped, a downward readjustment of the dosage of insulin or oral hypoglycemic agent may be necessary to avoid hypoglycemia. At all times, close monitoring of urinary glucose levels is mandatory in such patients.
4. In case of concomitant oral anticoagulant therapy, the prothrombin time should be measured frequently to determine if the dosage of oral anticoagulants is to be readjusted.
5. Partial loss of hair may be experienced by children in the first few months of thyroid therapy, but this is usually a transient phenomenon and later recovery is usually the rule.