Indications and Usage
NP Thyroid ®tablets (thyroid tablets, USP) are indicated:
1. As replacement or supplemental therapy in patients with hypothyroidism of any etiology, except transient hypothyroidism during the recovery phase of subacute thyroiditis. This category includes cretinism, myxedema, and ordinary hypothyroidism in patients of any age (children, adults, the elderly), or state (including pregnancy); primary hypothyroidism resulting from functional deficiency, primary atrophy, partial or total absence of thyroid gland, or the effects of surgery, radiation, or drugs, with or without the presence of goiter; and secondary (pituitary), or tertiary (hypothalamic) hypothyroidism (See WARNINGS).
2. As pituitary TSH suppressants, in the treatment or prevention of various types of euthyroid goiters, including thyroid nodules, subacute or chronic lymphocytic thyroiditis (Hashimoto’s), multinodular goiter, and in the management of thyroid cancer.
Dosage and Administration
The dosage of thyroid hormones is determined by the indication and must in every case be individualized according to patient response and laboratory findings.
Biotin supplementation may interfere with immunoassays for TSH, T 4, and T 3, resulting in erroneous thyroid hormone test results. Inquire whether patients are taking biotin or biotin-containing supplements. If so, advise them to stop biotin supplementation at least 2 days before assessing TSH and/or T 4levels (see PRECAUTIONS).
Thyroid hormones are given orally. In acute, emergency conditions, injectable levothyroxine sodium may be given intravenously when oral administration is not feasible or desirable, as in the treatment of myxedema coma, or during total parenteral nutrition. Intramuscular administration is not advisable because of reported poor absorption.
Hypothyroidism- Therapy is usually instituted using low doses, with increments which depend on the cardiovascular status of the patient. The usual starting dose is 30 mg NP Thyroid®, with increments of 15 mg every 2 to 3 weeks. A lower starting dosage, 15 mg/day, is recommended in patients with long standing myxedema, particularly if cardiovascular impairment is suspected, in which case extreme caution is recommended. The appearance of angina is an indication for a reduction in dosage. Most patients require 60 to 120 mg/day. Failure to respond to doses of 180 mg suggests lack of compliance or malabsorption. Maintenance dosages 60 to 120 mg/day usually result in normal serum levothyroxine (T 4) and triiodothyronine (T 3) levels. Adequate therapy usually results in normal TSH and T 4levels after 2 to 3 weeks of therapy.
Readjustment of thyroid hormone dosage should be made within the first four weeks of therapy, after proper clinical and laboratory evaluations, including serum levels of T 4, bound and free, and TSH.
T 3may be used in preference to levothyroxine (T 4) during radio-isotope scanning 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 T 4and T 3is suspected.
Myxedema Coma- Myxedema coma is usually precipitated in the hypothyroid patient of long-standing by intercurrent illness or drugs such as sedatives and anesthetics and should be considered a medical emergency. Therapy should be directed at the correction of electrolyte disturbances and possible infection besides the administration of thyroid hormones. Corticosteroids should be administered routinely. T 4and T 3may be administered via a nasogastric tube but the preferred route of administration of both hormones is intravenous. Levothyroxine sodium (T 4) is given at 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 intravenously. Normal T 4levels are achieved in 24 hours followed in 3 days by threefold elevation of T 3. 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- Exogenous thyroid hormone may produce regression of metastases from follicular and papillary carcinoma of the thyroid and is used as ancillary therapy of these conditions with radioactive 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 of endogenous hormone. 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 Graves ophthalmopathy. 131I uptake is determined before and after the administration of the exogenous hormone. A 50% or greater suppression of uptake indicates a normal thyroid-pituitary axis and thus rules out thyroid gland autonomy.
For adults, the usual suppressive dose of levothyroxine (T 4) is 1.56 mcg/kg of body weight per day given for 7 to 10 days. These doses usually yield normal serum T 4and T 3levels 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 with congenital hypothyroidism, therapy with full doses should be instituted as soon as the diagnosis has been made.
| NP Thyroid® Tablets | ||
| Age | Dose per day | Daily dose per kg of body weight |
| 0 - 6 mos. | 15 - 30 mg | 4.8 - 6 mg |
| 6 - 12 mos. | 30 - 45 mg | 3.6 - 4.8 mg |
| 1 - 5 yrs. | 45 - 60 mg | 3 - 3.6 mg |
| 6 - 12 yrs. | 60 - 90 mg | 2.4 - 3 mg |
| Over 12 yrs. | Over 90 mg | 1.2 - 1.8 mg |
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 from the literature, however, of true allergic or idiosyncratic reactions to thyroid hormone.
Adverse Reactions
Adverse reactions other than those indicative of hyperthyroidism because of therapeutic overdosage, either initially or during the maintenance period, are rare (See OVERDOSAGE).
Drug Interactions
Drug Interactions
Oral Anticoagulants— Thyroid hormones appear to increase catabolism of vitamin K-dependent clotting factors. If oral anticoagulants are also being given, compensatory increases in clotting factor synthesis are impaired. Patients stabilized on oral anticoagulants who 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 in anticoagulant dosage 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.
Insulin or Oral Hypoglycemics— 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 hypoglycemics should be closely watched during initiation of thyroid replacement therapy.
Cholestyramine or Colestipol- Cholestyramine or colestipol binds both T 4and T 3in the intestine, thus impairing absorption of these thyroid hormones. In vitrostudies indicate that the binding is not easily removed. Therefore, four to five hours should elapse between administration of cholestyramine and thyroid hormones.
Estrogen, Oral Contraceptives— Estrogens tend to increase serum thyroxine-binding globulin (TBg). In a patient with a nonfunctioning thyroid gland who is receiving thyroid replacement therapy, free levothyroxine 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 will result in a compensatory increase in levothyroxine 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.
Overdosage
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.
Treatment of Overdosage- Dosage should be reduced or therapy temporarily discontinued if signs and symptoms of overdosage appear. Treatment may be reinstituted at a lower dosage. In normal individuals, normal hypothalamic-pituitary-thyroid axis function is restored in 6 to 8 weeks after thyroid suppression.
Treatment of acute massive thyroid hormone overdosage is aimed at reducing gastrointestinal absorption 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 and ventilation maintained. Cardiac glycosides may be indicated if congestive heart failure develops. 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.
Other adjunctive measures may include administration of cholestyramine to interfere with thyroxine absorption, and glucocorticoids to inhibit conversions of T 4to T 3.
Description
NP Thyroid ®(thyroid tablets, USP) for oral use is a natural preparation derived from porcine thyroid glands. They contain both tetraiodothyronine sodium (T 4levothyroxine) and triiodothyronine sodium (T 3liothyronine) providing 38 mcg levothyroxine (T 4) and 9 mcg liothyronine (T 3) per grain of thyroid. The inactive ingredients are calcium stearate, dextrose (agglomerated) and mineral oil. Contains no ingredient made from a gluten-containing grain (wheat, barley, rye).
Clinical Pharmacology
The steps in the synthesis of the thyroid hormones are controlled by thyrotropin (Thyroid Stimulating Hormone, TSH) secreted by the anterior pituitary. This hormone’s secretion is in turn controlled by a feedback mechanism effected by the thyroid hormones themselves and by thyrotropin releasing hormone (TRH), a tripeptide of 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 their physiologic action are not well understood. These hormones enhance oxygen consumption by most tissues of the body, increase the basal metabolic rate, and the metabolism of carbohydrates, 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 the central nervous system.
The normal thyroid gland contains approximately 200 mcg of levothyroxine (T 4) per gram of gland, and 15 mcg of liothyronine (T 3) per gram. The ratio of these two hormones in the circulation does not represent the ratio in the thyroid gland, since about 80 % of peripheral liothyronine (T 3) comes from monodeiodination of levothyroxine. Peripheral monodeiodination of levothyroxine at the 5 position (inner ring) also results in the formation of reverse liothyronine (T 3), which is calorigenically inactive.
Liothyronine (T 3) levels are low in the fetus and newborn, in old age, in chronic caloric deprivation, hepatic cirrhosis, renal failure, surgical stress, and chronic illnesses representing what has been called the “T 3thyronine syndrome.”
How Supplied / Storage and Handling
NP Thyroid ®tablets (thyroid tablets, USP) are available as:
- 15 mg (1/4 gr) NDC 42192-327-30 in 30-count bottle NDC 42192-327-90 in 90-count bottle NDC 42192-327-01 in 100-count bottle
- 30 mg (1/2 gr) NDC 42192-329-30 in 30-count bottle NDC 42192-329-90 in 90-count bottle NDC 42192-329-01 in 100-count bottle NDC 42192-329-10 in 1000-count bottle
- 60 mg (1 gr) NDC 42192-330-30 in 30-count bottle NDC 42192-330-90 in 90-count bottle NDC 42192-330-01 in 100-count bottle NDC 42192-330-10 in 1000-count bottle
- 90 mg (1 1/2 gr) NDC 42192-331-30 in 30-count bottle NDC 42192-331-90 in 90-count bottle NDC 42192-331-01 in 100-count bottle NDC 42192-331-10 in 1000-count bottle
- 120 mg (2 gr) NDC 42192-328-30 in 30-count bottle NDC 42192-328-90 in 90-count bottle NDC 42192-328-01 in 100-count bottle
NP Thyroid ®tablets are available in the following strengths:
- 15 mg (1/4 grain) - tan, oval-shaped tablet, debossed on one side with “AP” and “327” on the other side.
- 30 mg (1/2 grain) – tan, round tablet, debossed on one side with “AP” and “329” on the other side.
- 60 mg (1 grain) – tan, round tablet, debossed on one side with “AP” and “330” on the other side.
- 90 mg (1 1/2 grain) – tan, round tablet, debossed on one side with “AP” and “331” on the other side.
- 120 mg (2 grain) – tan, round tablet, debossed on one side with “AP” and “328” on the other side.
Patient Counseling Information
Information for the Patient- 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, increased pulse rate, palpitations, excessive sweating, heat intolerance, nervousness, or any other unusual event.
3. In case of concomitant diabetes mellitus, 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. Instruct patients to discontinue biotin or any biotin-containing supplements for at least 2 days before thyroid function testing is conducted.
6. 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.