Synthroid drug properties and clinical applications

Synthroid, Drug Profile

SYNTHROID® (levothyroxine sodium tablets, USP) is an important drug, used to treat hypothyroidism. Synthroid has been extensively studied for over 42 years. It is the most widely prescribed thyroid medicine in the United States. Currently, over eight million people are using Synthroid for thyroid replacement therapy. [Abbott, 2001]

Synthetic Levothyroxine (T4 ) is identical in chemical composition and molecular weight to naturally secreted T4. Synthroid tablets contain the following inactive ingredients: acacia, confectioner's sugar, lactose, magnesium stearate, povidone, talc, and color additives.[Abbott, 2001].

Synthroid is pregnancy category A. Studies have shown that Synthroid increases the risk of fetal abnormalities if given during pregnancy. The possibility of fetal harm does appear to be remote, however, Synthroid should only given during pregnancy if it is clearly needed [Abbott, 2001]. In addition Abbot Laboratories reports that thyroid hormones do cross the placental barrier to some extent. T4 levels in the cord blood of a thyroid fetuses have been shown to be about one-third of maternal levels. This could cause hypothyroidism in the developing fetus.

Hypothyroidism during pregnancy is associated with a higher rate of complications, including spontaneous abortion and preeclampsia. It has been reported to have an adverse effect on fetal and childhood development. On the basis of current knowledge, Synthroid should not be discontinued during pregnancy, and hypothyroidism diagnosed during pregnancy should be treated. [Abbott, 2001].

Minimal amounts of thyroid hormones are excreted in human milk. Thyroid hormones are not associated with serious adverse reactions and do not have known tumor-producing potential. While caution should be exercised when Synthroid is administered to a nursing woman, adequate replacement doses of levothyroxine sodium are generally needed to maintain normal lactation. .[Abbott, 2001]

The starting dose of Synthroid, the frequency of the dose, and the optimal dosage must be determined on an individual basis. The proper dosage will be influenced by such factors as age, weight, cardiovascular status, presence of other illness, and the severity and duration of hypothyroid symptoms. The usual full replacement dose of Synthroid for younger, healthy adults is approximately 1.6 mug/kg/day administered once daily. In the elderly, the full replacement dose may be altered by decreases in T4 metabolism and levothyroxine sodium absorption. Older patients may require less than 1 mcg/kg/day. Children generally require higher doses. Women who are maintained on Synthroid during pregnancy may require increased doses. Few patients require doses greater than 200 mcg/day. [Abbott, 2001]

Once optimal replacement is achieved, clinical and laboratory evaluations should be conducted at least annually or whenever warranted by a change in patient status. In general, Synthroid should be given in the smallest dose that will achieve the desired clinical response.

The synthesis and secretion of the major thyroid hormones, L-thyroxine (T4) and L- triiodothyronine (T3), from the normally functioning thyroid gland are regulated by complex feedback mechanisms. TSH secretion is in turn controlled by thyrotropin-releasing hormone (TRH) produced in the hypothalamus, circulating thyroid hormones, and possibly other mechanisms. When serum concentrations of T3 and T4 are increased, secretion of TSH and TRH decreases. Conversely, when serum thyroid hormone concentrations are decreased, secretion of TSH and TRH is increased. Administration of extra thyroid hormones to certain individuals results in suppression of thyroid hormone secretion. .[Abbott, 2001]

T4 is not absorbed from the stomach and little, if any, drug is absorbed from the duodenum. A number of human studies have confirmed the importance of an intact jejunum and ileum for T4, absorption and have shown some absorption from the duodenum. [Abbott, 2001]

Distribution of thyroid hormones in human body tissues and fluids has not been fully studied. In man, approximately 20 to 40% of T4 is eliminated in the stool. About 70% of the T4 secreted daily to yield equal amounts of T3 and rT3. [Abbott, 2001]

The pharmacodynamics of Synthroid have been studied, but with inconclusive results. The onset, peak, and duration of the effects of Synthroid age are highly dependent upon many variables and will differ with each individual case. Decreased absorption may result from administration of infant soybean formula, ferrous sulfate, sodium polystyrene sulfonate, aluminum hydroxide, sucralfate, or bile acid suppressants. [Abbott, 2001].

Forms of Synthroid produced by different manufacturers have not been proven to be interchangeable by the FDA. If a patient switches brands of Synthroid, they must be re-tested and re-evaluated. [Banahan, 1998]

Some vitamins and other medications may either increase the absorption rate or prevent the absorption of Synthroid. The SYNTHROID PI contains the following statement: "The following agents may bind and increase absorption of levothyroxine sodium from the gastrointestinal tract: aluminum hydroxide, cholestyramine resin, colestipol hydrochloride, ferrous sulfate, sodium polystyrene sulfonate, soybean flour (e. g., infant formula), sucralfate" [BASF, 2000]

Many doctors recommend that for best absorption of your thyroid hormone, take it first thing the morning, on an empty stomach, and wait one hour before eating, and at least two hours before taking any vitamin with iron. [BASF, 2000]

Synthroid should not be used for the treatment of obesity, and should not be taken by patients with untreated thyrotoxicosis (excess of thyroid hormone), uncorrected adrenal insufficiency, or apparent hypersensitivity to thyroid hormones or any inactive product constituents. [Abbott, 2001]

Synthroid should not be given to patients untreated thyrotoxicosis of any form or an apparent hypersensitivity to thyroid hormones or any of the inactive product constituents. Synthroid should also not be given to patients with uncorrected adrenal insufficiency. Synthroid should be used with caution in patients with cardiovascular disorders, including angina, coronary artery disease, and hypertension, and in the elderly who have a greater likelihood of cardiac disease. The use of Synthroid in patients with diabetes mellitus, diabetes insipidus or adrenal disorders may aggravate the intensity of their symptoms. [Abbott, 2001]

Adverse reactions other than those indicative of thyrotoxicosis as a result of therapeutic overdosage, either initially or during the maintenance periods, are rare Hypersensitivity reactions to the product additives, such as rash and urticaria, may occur. Partial hair loss may occur during the initial months of therapy, but generally goes away with time. The incidence of continued hair loss is unknown. Pseudotumor cerebri (seizure) has been reported in pediatric patients receiving thyroid hormone replacement therapy [Abbott, 2001]

Excessive doses of Synthroid result in a hypermetabolic state indistinguishable from thyrotoxicosis of natural origin. Signs and symptoms of thyrotoxicosis include weight loss, increased appetite, palpitations, nervousness, diarrhea, abdominal cramps, sweating, tachycardia, increased pulse and blood pressure, cardiac arrhythmias, tremors, insomnia, heat intolerance, fever, and menstrual irregularities. Symptoms are not always evident or may not appear until several days after ingestion. [Abbott, 2001]