Synthroid Information
Synthroid (Levothyroxine) Description
Synthroid (Levothyroxine) (levothyroxine sodium tablets, USP) contain synthetic crystalline L-3,3',5,5'-tetraiodothyronine sodium salt [levothyroxine (T) sodium]. Synthetic T is identical to that produced in the human thyroid gland. Levothyroxine (T) sodium has an empirical formula of CHIN NaO
HO, molecular weight of 798.86 g/mol (anhydrous), and structural formula as shown:
Acacia, confectioner's sugar (contains corn starch), lactose monohydrate, magnesium stearate, povidone, and talc. The following are the color additives by tablet strength:
*Note – FD&C Yellow No. 6 is orange in color.
Meets USP Dissolution Test 3
Synthroid (Levothyroxine) 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 (T) and L-triiodothyronine (T), by the thyroid gland. Circulating serum T and T levels exert a feedback effect on both TRH and TSH secretion. When serum T and T levels increase, TRH and TSH secretion decrease. When thyroid hormone levels decrease, TRH and TSH secretion increase.
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. T and T 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 T, the majority of which (approximately 80%) is derived from T 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 , , and ).
Synthroid (Levothyroxine) Indications And Usage
Levothyroxine sodium is used for the following indications:
Synthroid (Levothyroxine) Contraindications
Levothyroxine is contraindicated in patients with untreated subclinical (suppressed serum TSH level with normal T and T 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 ). Synthroid (Levothyroxine) is contraindicated in patients with hypersensitivity to any of the inactive ingredients in Synthroid (Levothyroxine) tablets (See ).
Synthroid (Levothyroxine) Warnings
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WARNING: Thyroid hormones, including Synthroid (Levothyroxine) , either alone or with other therapeutic agents, should not be used for the treatment of obesity or for weight loss. 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.
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 ). If the serum TSH level is not suppressed, Synthroid (Levothyroxine) 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.
Synthroid (Levothyroxine) Precautions
Many drugs affect thyroid hormone pharmacokinetics and metabolism (e.g., absorption, synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to Synthroid (Levothyroxine) . In addition, thyroid hormones and thyroid status have varied effects on the pharmacokinetics and actions of other drugs. A listing of drug-thyroidal axis interactions is contained in Table 2.
The list of drug-thyroidal axis interactions in Table 2 may not be comprehensive due to the introduction of new drugs that interact with the thyroidal axis or the discovery of previously unknown interactions. The prescriber should be aware of this fact and should consult appropriate reference sources (e.g., package inserts of newly approved drugs, medical literature) for additional information if a drug-drug interaction with levothyroxine is suspected.
Synthroid (Levothyroxine) Adverse Reactions
Adverse reactions associated with levothyroxine therapy are primarily those of hyperthyroidism due to therapeutic overdosage (see and ). They include the following:
Pseudotumor cerebri and slipped capital femoral epiphysis have been reported in children receiving levothyroxine therapy. Overtreatment may result in craniosynostosis in infants and premature closure of the epiphyses in children with resultant compromised adult height.
Seizures have been reported rarely with the institution of levothyroxine therapy.
Inadequate levothyroxine dosage will produce or fail to ameliorate the signs and symptoms of hypothyroidism.
Hypersensitivity reactions to inactive ingredients have occurred in patients treated with thyroid hormone products. These include urticaria, pruritus, skin rash, flushing, angioedema, various GI symptoms (abdominal pain, nausea, vomiting and diarrhea), fever, arthralgia, serum sickness and wheezing. Hypersensitivity to levothyroxine itself is not known to occur.
Synthroid (Levothyroxine) Overdosage
The signs and symptoms of overdosage are those of hyperthyroidism (see and ). In addition, confusion and disorientation may occur. Cerebral embolism, shock, coma, and death have been reported. Seizures have occurred in a child ingesting 18 mg of levothyroxine. Symptoms may not necessarily be evident or may not appear until several days after ingestion of levothyroxine sodium.
Synthroid (Levothyroxine) Dosage And Administration
The goal of replacement therapy is to achieve and maintain a clinical and biochemical euthyroid state. The goal of suppressive therapy is to inhibit growth and/or function of abnormal thyroid tissue. The dose of Synthroid (Levothyroxine) that is adequate to achieve these goals depends on a variety of factors including the patient's age, body weight, cardiovascular status, concomitant medical conditions, including pregnancy, concomitant medications, and the specific nature of the condition being treated (see and ). Hence, the following recommendations serve only as dosing guidelines. Dosing must be individualized and adjustments made based on periodic assessment of the patient's clinical response and laboratory parameters (see ).
Synthroid (Levothyroxine) is administered as a single daily dose, preferably one-half to one-hour before breakfast. Synthroid (Levothyroxine) should be taken at least 4 hours apart from drugs that are known to interfere with its absorption (see ).
Due to the long half-life of levothyroxine, the peak therapeutic effect at a given dose of levothyroxine sodium may not be attained for 4-6 weeks.
Caution should be exercised when administering Synthroid (Levothyroxine) to patients with underlying cardiovascular disease, to the elderly, and to those with concomitant adrenal insufficiency (see ).
Synthroid (Levothyroxine)
Synthroid (Levothyroxine)
Synthroid (Levothyroxine)
Synthroid (Levothyroxine)
