THYROID TABLETS
Thyroid tablets USP) for oral use are natural
preparations derived from porcine thyroid glands (T3 liothyronine is
approximately four times as potent as T4 levothyroxine on a micro- gram for
microgram basis). They provide 38-mcg levothyroxine (T4) and 9-mcg liothyronine
(T3) per grain of thyroid.
The inactive ingredients are calcium stearate,
dextrose, microcrystalline cellulose sodium starch glycolate and opadry white.
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
200mcg 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
monodeidination (T4) at the 5th position (inner ring) also results in the
formation of reverse (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 and
thereby makes 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 10 Serum proteins, including thyroid-binding globulin (TBg),
thyroid-binding prealbumin (TBPA), and albumin (TBa), whose capacities and
affinities vary for the hormones. The higher affinity 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
Armour Thyroid tablets are indicated
1. As replacement or supplemental therapy in
patients with hypothroidism of any etiology, except transient hypothyrodism
during the recovery phase of subacute thyroiditis. This category includes
cretinism, myxedema and ordinary hypothyroidism in patients of any age
(children, adults, and 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 autonomy.
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
Information for the patients:-
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, heal intolerance,
nervousness, or any other unusual event.
3. In case of concomitant diabetes mellitus, the
daily dosage of anti diabetic 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.
Adverse Reactions
Adverse reactions other than those indicative of
hyperthyroidism because of therapeutic overdose, either initially or during the
maintenance period are rare (See OVERDOSAGE)
Overdosage
Sign 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 over dosage - Dosage should be
reduced or therapy temporarily discontinued if signs and symptoms of over dosage
appear.
Treatment may be re-instituted at a lower dosage.
In normal individuals, normal hypothalamic pituitary thyroid axis functions is
restored in 6 to 8 weeks after thyroid suppression.
Treatment of acute massive thyroid hormone over
dosage is aimed at reducing gastro intestinal absorption of the drugs and
counteracting central and peripheral effects, mainly those of increased
sympathetic activity. Vomiting may be induced initially if further gastro
intestinal 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 of congestive heart failure
develops. Measures to control fever, hypoglycemia or fluid loss should be
instituted if needed. Anti adrenergic 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 per day, initially especially when no
contraindications exits for its use. Other adjunctive measure may include
administration of cholestyramine to interfere with thyroxine absorption, and
glucocorticoids to inhibit conversion of T4 or T3.
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 total parenteral nutrition. Intramuscular
administration is not advisable because of reported poor absorption.
Hypothyroidism – Therapy is usually
instituted using low doses the increments that depend on the cardiovascular
status of the patient. The usual starting dose is 30 mg with increments of 15 mg
every 2 to 3 weeks. A lower starting dosage, 15 mg per 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 per day. Failure to respond to doses of 180 mg suggests lack of
compliance or malabsorption. Maintenance dosages 60 to 120 mg per day usually
result in normal serum T4 and T3 levels. Adequate therapy usually results in
normal TSH and T4 levels 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 T4, bound and free and TSH.
Liothyronine may be used in preference to
levothyroxine during radioisotope 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
and liothyronine is 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. (T4) and (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 that those used for replacement
therapy are required. Medullary carcinoma of the thyroid is usually unresponsive
to this therapy.
Pediatric Dosage – Pediatric dosage
should follow the recommendations. In infants with congenital hypothyroidism,
therapy with full doses should be instituted as soon as the diagnosis has been
made.
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