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LEVOTHYROXINE SODIUM - levothyroxine 25 mcg tablets


LEVOTHYROXINE SODIUM-levothyroxine 25 mcg tablets

LEVOTHYROXINE SODIUM - levothyroxine sodium tablet
Patheon Puerto Rico, Inc.
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Levothyroxine Sodium Tablets, USP
Rx ONLY
DESCRIPTION
Levothyroxine sodium tablets, USP contains synthetic crystalline L-3,3',5,5'-tetraiodothyronine sodium salt [levothyroxine (T4)
sodium]. Synthetic T4 is identical to that produced in the human thyroid gland.
Levothyroxine (T4) sodium has an empirical formula of C15H10I4N NaO4 x H2O, molecular weight of 798.86 g/mol (anhydrous), and
structural formula as shown:
Inactive Ingredients
Magnesium Stearate, NF; Microcrystalline Cellulose, NF; Colloidal Silicone Dioxide, NF; Sodium Starch Glycolate, NF. The
following are the color additives by tablet strength:
Strength (mcg) Color Additive(s)
25 FD&C Yellow No. 6 Aluminum Lake
50 None
75 FD&C Blue No. 2 Aluminum Lake
D&C Red No. 27 Aluminum Lake
88 FD&C Blue No. 1 Aluminum Lake
D&C Yellow No. 10 Aluminum Lake
D&C Red No. 30 Aluminum Lake
100 D&C Yellow No. 10 Aluminum Lake
D&C Red Lake Blend (D&C Red No. 27
Lake and D&C Red No. 30 Lake)
112 D&C Red No. 27 Aluminum Lake
D&C Red No. 30 Aluminum Lake
125 FD&C Yellow No. 6 Aluminum Lake
FD&C Red No. 40 Aluminum Lake
FD&C Blue No. 1 Aluminum Lake
137 FD&C Blue No. 1 Aluminum Lake
150 FD&C Blue No. 2 Aluminum Lake
175 D&C Red No. 27 Aluminum Lake
D&C Red No. 30 Aluminum Lake
FD&C Blue No. 1 Aluminum Lake
200 D&C Yellow No. 10 Aluminum Lake
D&C Red No. 27 Aluminum Lake
300 D&C Yellow No. 10 Aluminum Lake
FD&C Yellow No. 6 Aluminum Lake
FD&C Blue No. 1 Aluminum Lake
Meets USP Dissolution Test 2
CLINICAL PHARMACOLOGY
Thyroid hormone synthesis and secretion is regulated by the hypothalamic-pituitary-thyroid axis. Thyrotropin-releasing hormone
(TRH) released from the hypothalamus stimulates secretion of thyrotropin-stimulating hormone, TSH, from the anterior pituitary.
TSH, in turn, is the physiologic stimulus for the synthesis and secretion of thyroid hormones, L-thyroxine (T4) and L-triiodothyronine
(T3), by the thyroid gland. Circulating serum T3 and T4 levels exert a feedback effect on both TRH and TSH secretion. When serum
T3 and T4 levels increase, TRH and TSH secretion decrease. When thyroid hormone levels decrease, TRH and TSH secretion
increase.
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The mechanisms by which thyroid hormones exert their physiologic actions are not completely understood, but it is thought that their
principal effects are exerted through control of DNA transcription and protein synthesis. T3 and T4 diffuse into the cell nucleus and
bind to thyroid receptor proteins attached to DNA. This hormone nuclear receptor complex activates gene transcription and synthesis
of messenger RNA and cytoplasmic proteins.
Thyroid hormones regulate multiple metabolic processes and play an essential role in normal growth and development, and normal
maturation of the central nervous system and bone. The metabolic actions of thyroid hormones include augmentation of cellular
respiration and thermogenesis, as well as metabolism of proteins, carbohydrates and lipids. The protein anabolic effects of thyroid
hormones are essential to normal growth and development.
The physiological actions of thyroid hormones are produced predominantly by T3, the majority of which (approximately 80%) is
derived from T4 by deiodination in peripheral tissues.
Levothyroxine, at doses individualized according to patient response, is effective as replacement or supplemental therapy in
hypothyroidism of any etiology, except transient hypothyroidism during the recovery phase of subacute thyroiditis.
Levothyroxine is also effective in the suppression of pituitary TSH secretion in the treatment or prevention of various types
of euthyroid goiters, including thyroid nodules, Hashimoto's thyroiditis, multinodular goiter and, as adjunctive therapy in the
management of thyrotropin-dependent well-differentiated thyroid cancer (see INDICATIONS AND USAGE, PRECAUTIONS,
DOSAGE AND ADMINISTRATION).
PHARMACOKINETICS
Absorption - Absorption of orally administered T4 from the gastrointestinal (GI) tract ranges from 40% to 80%. The majority of the
levothyroxine dose is absorbed from the jejunum and upper ileum. The relative bioavailability of this brand of Levothyroxine sodium
tablets, USP product, compared to an equal nominal dose of oral levothyroxine sodium solution, is approximately 99 %. T4 absorption
is increased by fasting, and decreased in malabsorption syndromes and by certain foods such as soybean infant formula. Dietary fiber
decreases bioavailability of T4. Absorption may also decrease with age. In addition, many drugs and foods affect T4 absorption (see
PRECAUTIONS, Drug Interactions and Drug-Food Interactions).
Distribution - Circulating thyroid hormones are greater than 99% bound to plasma proteins, including thyroxine-binding globulin
(TBG), thyroxine-binding prealbumin (TBPA), and albumin (TBA), whose capacities and affinities vary for each hormone. The higher
affinity of both TBG and TBPA for T4 partially explains the higher serum levels, slower metabolic clearance, and longer half-life of
T4 compared to T3. Protein-bound thyroid hormones exist in reverse equilibrium with small amounts of free hormone. Only unbound
hormone is metabolically active. Many drugs and physiologic conditions affect the binding of thyroid hormones to serum proteins
(see PRECAUTIONS, Drug Interactions and Drug-Laboratory Test Interactions). Thyroid hormones do not readily cross the
placental barrier (see PRECAUTIONS, Pregnancy).
Metabolism - T4 is slowly eliminated (see Table 1). The major pathway of thyroid hormone metabolism is through sequential
deiodination. Approximately eighty-percent of circulating T3 is derived from peripheral T4 by monodeiodination. The liver is the
major site of degradation for both T4 and T3, with T4 deiodination also occurring at a number of additional sites, including the kidney
and other tissues. Approximately 80% of the daily dose of T4 is deiodinated to yield equal amounts of T3 and reverse T3 (rT3). T3 and
rT3 are further deiodinated to diiodothyronine. Thyroid hormones are also metabolized via conjugation with glucuronides and sulfates
and excreted directly into the bile and gut where they undergo enterohepatic recirculation.
Elimination - Thyroid hormones are primarily eliminated by the kidneys. A portion of the conjugated hormone reaches the colon
unchanged and is eliminated in the feces. Approximately 20% of T4 is eliminated in the stool. Urinary excretion of T4 decreases with
age.
Table 1: Pharmacokinetic Parameters of Thyroid Hormones in Euthyroid Patients
Hormone Ratio in Thyroglobulin Biologic Potency t1/2 (days) Protein Binding (%)2
Levothyroxine (T4) 10 - 20 1 6-71 99.96
Liothyronine (T3) 1 4 2 99.5
1 3 to 4 days in hyperthyroidism, 9 to 10 days in hypothyroidism; 2 Includes TBG, TBPA, and TBA
INDICATIONS AND USAGE
Levothyroxine sodium is used for the following indications:
Hypothyroidism - As replacement or supplemental therapy in congenital or acquired hypothyroidism of any etiology, except transient
hypothyroidism during the recovery phase of subacute thyroiditis. Specific indications include: primary (thyroidal), secondary
(pituitary), and tertiary (hypothalamic) hypothyroidism and subclinical hypothyroidism. Primary hypothyroidism may result from
functional deficiency, primary atrophy, partial or total congenital absence of the thyroid gland, or from the effects of surgery,
radiation, or drugs, with or without the presence of goiter.
Pituitary TSH Suppression - In the treatment or prevention of various types of euthyroid goiters (see WARNINGS and
PRECAUTIONS), including thyroid nodules (see WARNINGS and PRECAUTIONS), subacute or chronic lymphocytic thyroiditis
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(Hashimoto's thyroiditis), multinodular goiter (see WARNINGS and PRECAUTIONS) and, as an adjunct to surgery and radioiodine
therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer.
CONTRAINDICATIONS
Levothyroxine is contraindicated in patients with untreated subclinical (suppressed serum TSH level with normal T3 and T4 levels) or
overt thyrotoxicosis of any etiology and in patients with acute myocardial infarction. Levothyroxine is contraindicated in patients with
uncorrected adrenal insufficiency since thyroid hormones may precipitate an acute adrenal crisis by increasing the metabolic clearance
of glucocorticoids (see PRECAUTIONS). Levothyroxine sodium tablets, USP is contraindicated in patients with hypersensitivity to
any of the inactive ingredients in Levothyroxine sodium tablets, USP (see DESCRIPTION, Inactive Ingredients.)
WARNINGS
WARNING: Thyroid hormones, including Levothyroxine sodium tablets, USP, either alone or with other therapeutic agents, should no
hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life threatening manifestations o
effects.
Levothyroxine sodium should not be used in the treatment of male or female infertility unless this condition is associated with
hypothyroidism.
In patients with nontoxic diffuse goiter or nodular thyroid disease, particularly the elderly or those with underlying cardiovascular
disease, levothyroxine sodium therapy is contraindicated if the serum TSH level is already suppressed due to the risk of precipitating
overt thyrotoxicosis (see CONTRAINDICATIONS). If the serum TSH level is not suppressed, Levothyroxine sodium tablets, USP
should be used with caution in conjunction with careful monitoring of thyroid function for evidence of hyperthyroidism and clinical
monitoring for potential associated adverse cardiovascular signs and symptoms of hyperthyroidism.
PRECAUTIONS
General
Levothyroxine has a narrow therapeutic index. Regardless of the indication for use, careful dosage titration is necessary to avoid
the consequences of over- or under-treatment. These consequences include, among others, effects on growth and development,
cardiovascular function, bone metabolism, reproductive function, cognitive function, emotional state, gastrointestinal function, and
on glucose and lipid metabolism. Many drugs interact with levothyroxine sodium, necessitating adjustments in dosing to maintain
therapeutic response (see Drug Interactions).
Effects on bone mineral density- In women, long-term levothyroxine sodium therapy has been associated with increased bone
resorption, thereby decreasing bone mineral density, especially in post-menopausal women on greater than replacement doses or
in women who are receiving suppressive doses of levothyroxine sodium. The increased bone resorption may be associated with
increased serum levels and urinary excretion of calcium and phosphorous, elevations in bone alkaline phosphatase and suppressed
serum parathyroid hormone levels. Therefore, it is recommended that patients receiving levothyroxine sodium be given the minimum
dose necessary to achieve the desired clinical and biochemical response.
Patients with underlying cardiovascular disease- Exercise caution when administering levothyroxine to patients with
cardiovascular disorders and to the elderly in whom there is an increased risk of occult cardiac disease. In these patients, levothyroxine
therapy should be initiated at lower doses than those recommended in younger individuals or in patients without cardiac disease
(see WARNINGS;PRECAUTIONS, Geriatric Use; and DOSAGE AND ADMINISTRATION). If cardiac symptoms develop
or worsen, the levothyroxine dose should be reduced or withheld for one week and then cautiously restarted at a lower dose.
Overtreatment with levothyroxine sodium may have adverse cardiovascular effects such as an increase in heart rate, cardiac wall
thickness, and cardiac contractility and may precipitate angina or arrhythmias. Patients with coronary artery disease who are
receiving levothyroxine therapy should be monitored closely during surgical procedures, since the possibility of precipitating cardiac
arrhythmias may be greater in those treated with levothyroxine. Concomitant administration of levothyroxine and sympathomimetic
agents to patients with coronary artery disease may precipitate coronary insufficiency.
Patients with nontoxic diffuse goiter or nodular thyroid disease- Exercise caution when administering levothyroxine to patients
with nontoxic diffuse goiter or nodular thyroid disease in order to prevent precipitation of thyrotoxicosis (see WARNINGS). If the
serum TSH is already suppressed, levothyroxine sodium should not be administered (see CONTRAINDICATIONS).
Associated endocrine disorders
Hypothalamic/pituitary hormone deficiencies
In patients with secondary or tertiary hypothyroidism, additional hypothalamic/pituitary hormone deficiencies should be considered,
and, if diagnosed, treated (see PRECAUTIONS, Autoimmune polyglandular syndrome for adrenal insufficiency).
Autoimmune polyglandular syndrome
Occasionally, chronic autoimmune thyroiditis may occur in association with other autoimmune disorders such as adrenal
insufficiency, pernicious anemia, and insulin-dependent diabetes mellitus. Patients with concomitant adrenal insufficiency should be
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What are side effects of levothyroxine? Side effects not requiring immediate medical attention Abdominal or stomach cramps change in appetite crying diarrhea false or unusual sense of well-being fear or nervousness feeling not well or unhappy feeling of discomfort feeling of warmth feeling things are not real More items...