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Prescribing Information for Nature-Throid™ (Thyroid USP) Tablets
DESCRIPTION
Nature-Throid™ (Thyroid USP) Tablets, micro-coated, easy to swallow with a reduced odor, for
oral use are natural preparations derived from porcine thyroid glands (T3 liothyronine is
approximately four times as potent as T4 levothyroxine on 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
Carnauba Wax, Colloidal Silicon dioxide, Dicalcium Phosphate, Hypromellose, Lactose
Monohydrate*, Magnesium Stearate, Microcrystalline Cellulose, Polyethylene Glycol
(PEG)-400, Sodium Starch Glycolate, Stearic Acid.
*Present in traceable amount as part of Thyroid USP (diluent)
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 affected 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 (T4) per gram of
gland, and 15 mcg of liothyronine (T3) per gram. The ratio of these two hormones in the
circulation does 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, hepatic
cirrhosis, renal failure, surgical 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 the
gastrointestinal tract. The degree of absorption is dependent on the vehicle used for its
administration and by the character of the intestinal contents, the intestinal flora, including
plasma protein, and soluble dietary factors, all of which bind thyroid, thereby making it
unavailable for diffusion. Only 41 percent is absorbed when given in a gelatin capsule as
opposed to 74 percent absorption when given with an albumin carrier.
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 chole
styramine) 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 higher affinity of 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 the bile and gut where it may complete an enterohepatic circulation.
Eighty-five percent of levothyroxine (T4) metabolized daily is deiodinated.
INDICATIONS AND USAGE
1. As replacement of 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.
3. As diagnostic agents in suppression tests to differentiate suspected mild hyperthyroidism or
thyroid gland anatomy.
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 for the literature, however, of true allergic or idiosyncratic reactions to
thyroid hormone.
WARNINGS
Drugs with thyroid hormone activity, alone or together with other therapeutic agents, have been
used for the treatment of obesity. 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 their anorectic effects.
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 female infertility unless 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 the cardiovascular system, particularly the coronary arteries, is
suspected. These include patients with angina pectoris or the elderly, in whom there is a greater
likelihood of occult cardiac disease. In these patients therapy should be initiated with low doses,
i.e. 15–30 mg. When, in such patients, a euthyroid state can only be reached at the expense of
an aggravation of the cardiovascular disease, thyroid hormone dosage should be reduced.
Thyroid hormone therapy in patients with concomitant diabetes mellitus or diabetes insipidus or
adrenal cortical insufficiency 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 (See DOSAGE AND ADMINISTRATION).
Hypothyroidism decreases and hyperthyroidism increases the sensitivity to oral
anticoagulants. Prothrombin time should be closely monitored in thyroid treated patients on oral
anticoagulants and dosage of the latter agents adjusted on the basis of frequent
prothrombin time determinations. In infants, excessive doses of thyroid hormone preparations
may produce craniosynostosis.
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. 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.
Laboratory Tests: Treatment of patients with thyroid hormones requires 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. SerumT4 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 or radioimmunoassay are not influenced by blood levels of
organic or inorganic iodine.
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 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 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 Hypoglycemic-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- 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 (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 thyroid hormone 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 during infectious hepatitis. Decreases
in TBg concentrations are observed in nephrosis, acromegaly, and after androgen or
corticosteroid therapy. Familial hyper or hypothyroxine-binding-globulinemias 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.
Carcinogenesis, Mutagenesis, and Impairment of Fertility: A reportedly apparent association
between prolonged thyroid therapy and breast cancer has 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 evaluate carcinogenic potential,
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 any adverse effect on 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 of congenital hypothyroidism 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 or 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 young 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.
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).
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
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.
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.
Thyroid hormones are given orally. In acute, emergency condition, injectable levothyroxine
sodium (T4) 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, with increment of
15 mg every 2 to 3 weeks. A lower starting dosage, 15 mg/day, is recommended in patients with
longstanding myxedema, particularly if cardiovascular impairment is suspected, in which cause
extreme caution is recommended. The appearance of angina is an indication for
reduction in dosage. Most patients require 60–120 mg/day. Failure to respond to doses of
180 mg suggests lack of compliance or malabsorption. Maintenance dosages
60–120 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 of thyroid hormone dosage 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-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
levothyroxine (T4) and liothyronine (T3) is suspected.
Myxedema Coma: Myxedema coma is 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 of
electrolyte disturbances and possible infection besides the administration of thyroid
hormones. Corticosteroids should be administered routinely. Levothyroxine (T4) and
Liothyronine (T3) may be administered via a nasogastric 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: 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 is 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 Grave’s
ophthalmopathy. 1 uptake is determined before and after the administration of the exogenous
hormone. A fifty percent 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 (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 with congenital hypothyroidism therapy with full doses should be instituted as soon
as the diagnosis has been made.
HOW SUPPLIED
Nature-Throid™ (Thyroid USP) Tablets are supplied as follows:
16.25 mg. (1/4 gr.) in bottles of 100 Count (NDC 64727-3298-1), 990 Count Polybags (NDC 64727-3298-3),
1,000 Count (NDC 64727-3298-2), 1,008 Count Polybags (NDC 64727-3298-8)
32.5 mg (1/2 gr.) in bottles of 100 Count (NDC 64727-3299-1), 990 Count Polybags (NDC 64727-3299-3),
1,000 Count (NDC 64727-3299-2), 1,008 Count Polybags (NDC 64727-3299-8)
65 mg (1 gr.) in bottles of 100 Count (NDC 64727-3300-1), 990 Count Polybags (NDC 64727-3300-3),
1,000 Count (NDC 64727-3300-2), 1,008 Count Polybags (NDC 64727-3300-8)
130 mg (2 gr.) in bottles of 100 Count (NDC 64727-3308-1), 990 Count Polybags (NDC 64727-3308-3),
1,000 Count (NDC 64727-3308-2), 1,008 Count Polybags (NDC 64727-3308-8)
195 mg (3 gr.) in bottles of 100 Count (NDC 64727-3312-1), 990 Count Polybags (NDC 64727-3312-3),
1,000 Count (NDC 64727-3312-2), 1,008 Count Polybags (NDC 64727-3312-8)
STORAGE
Store at controlled room temperature; 15°-30°C (59°-86°F)
Dispense in tight, light-resistant containers as defined in the USP/NF. |
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