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Prescribing Information for Wes-Throid™ (Thyroid USP) Tablets
DESCRIPTION
Westhroid™ (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
Colloidal Silicon Dioxide, Dicalcium Phosphate,
Lactose Monohydrate*, Magnesium Stearate,
Microcrystalline Cellulose, Croscarmellose Sodium,
Stearic Acid, Opadry II 85F19316 Clear. *Present in
traceable amount as part of Thyroid USP (diluent) The
structural formulas of liothyronine (T3) and
levothyroxine (T4) are as follows:
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
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 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 in
the literature 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, whom
have a greater likelihood of occult cardiac 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 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 should be 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 thyroxinebinding 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 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.
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
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 during 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 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 angina 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 or malabsorption.
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 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 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 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.
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 3.3-6.0 mg
6 - 12 years 65 - 97.5 mg 2.4-3.0 mg
Over 12 years Over 97.5 mg 1.2-1.8 mg
HOW SUPPLIED:
Westhroid™ (Thyroid USP) Tablets are supplied as
follows:
16.25 mg. (1/4 gr.) in bottles of 100 Count (NDC
64727-7065-1), 1,000 Count
(NDC 64727-7065-2)
32.5 mg (1/2 gr.) in bottles of 100 Count (NDC
64727-7073-1), 990 Count
Polybags (NDC 64727-7073-3), 1,000 Count (NDC
64727-7073-2), 1,008
Count Polybags (NDC 64727-7073-8)
65 mg (1 gr.) in bottles of 100 Count (NDC
64727-7073-1), 990 Count
Polybags (NDC 64727-7073-3), 1,000 Count (NDC
64727-7073-2), 1,008
Count Polybags (NDC 64727-7073-8)
130 mg (2 gr.) in bottles of 100 Count (NDC
64727-7080-1), 990 Count
Polybags (NDC 64727-7080-3), 1,000 Count (NDC
64727-7080-2), 1,008
Count Polybags (NDC 64727-7080-8)
195 mg (3 gr.) in bottles of 100 Count (NDC
64727-7095-1), 1,000 Count (NDC
64727-7095-2)
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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