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
manifiestations 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.
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 liothyronine sodium therapy
should be initiated with low doses with due consideration
for its relatively rapid onset of action. Starting dosage
of Cytomel (liothyronine sodium) Tablets is 5 mcg daily,
and should be increased by no more than 5 mcg increments
at 2-week intervals. 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.
Morphologic hypogonadism and nephrosis should be ruled
out before the drug is administered. If hypopituitarism
is present, the adrenal deficiency must be corrected prior
to starting the drug.
Myxedematous patients are very sensitive to thyroid,
dosage should be started at a very low level and increased
gradually.
Severe and prolonged hypothyroidism can lead to a decreased
level of adrenocortical activity commensurate with the
lowered metabolic state. When thyroid-replacement therapy
is administered, the metabolism increases at a greater
rate than adrenocortical activity. This can precipitate
adrenocortical insufficiency. Therefore, in severe and
prolonged hypothyroidism, supplemental adrenocortical
steroids may be necessary. In rare instances the administration
of thyroid hormone may precipitate a hyperthyroid state
or may aggravate existing hyperthyroidism.
PRECAUTIONS
General
Thyroid hormone therapy in patients with concomitant
diabetes mellitus or insipidus or adrenal cortical insufficiency
aggravates the intensity of their symptoms. Appropriate
adjustments of the various therapeutic measures directed
at these concomitant endorcrine diseases are required.
The therapy of myxedema coma requires simultaneous administration
of glucocorticoids.
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
See PATIENT INFORMATION section.
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. Serum
T4 levels can be used to test the effectiveness of all
thyroid medications except products containing liothyronine
sodium. 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 and have
essentially replaced older tests of thyroid hormone measurements,
i.e. PBI, BEI and T4 by column.
Drug Interactions
See DRUG INTERACTIONS section.
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 T4 and 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 hypo-thyroxine-binding-globulinemias
have been described. The incidence of TBg deficiency approximates
1 in 9000. The binding of thyroxine by thyroxine-binding
prealbumin (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 reflective 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 nursmg woman.
Pediatric Use
Pregnant mothers provide little or no thyroid hormone
to the fetus. The incidence of congenital hypothyroidism
is relatively high (1:4000) and the hypothyroid fetus
would not derive any benefit from the small amounts of
hormone crossing the placental barrier. Routine determinations
of serum T4 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.
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