|Labeler Name||AbbVie Inc.|
|Dosage & Substance||tablet levothyroxine sodium|
|Date First Marketed||July 24, 2002|
SYNTHROID is indicated as a replacement therapy in primary (thyroidal), secondary (pituitary), and tertiary (hypothalamic) congenital or acquired hypothyroidism.
Pituitary Thyrotropin (Thyroid‑Stimulating Hormone, TSH) Suppression
SYNTHROID is indicated as an adjunct to surgery and radioiodine therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer.
- Limitations of Use:
- SYNTHROID is not indicated for suppression of benign thyroid nodules and nontoxic diffuse goiter in iodine-sufficient patients as there are no clinical benefits and overtreatment with SYNTHROID may induce hyperthyroidism(5.4)].
- SYNTHROID is not indicated for treatment of hypothyroidism during the recovery phase of subacute thyroiditis.
SYNTHROID is contraindicated in patients with uncorrected adrenal insufficiency.
Adverse reactions associated with SYNTHROID therapy are primarily those of hyperthyroidism due to therapeutic overdosage,. They include the following:
- fatigue, increased appetite, weight loss, heat intolerance, fever, excessive sweating
- headache, hyperactivity, nervousness, anxiety, irritability, emotional lability, insomnia
- tremors, muscle weakness, muscle spasm
- palpitations, tachycardia, arrhythmias, increased pulse and blood pressure, heart failure, angina, myocardial infarction, cardiac arrest
- diarrhea, vomiting, abdominal cramps, elevations in liver function tests
- hair loss, flushing, rash
- decreased bone mineral density
- menstrual irregularities, impaired fertility
Seizures have been reported rarely with the institution of levothyroxine therapy.
Adverse Reactions in Children
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.
Hypersensitivity reactions to inactive ingredients have occurred in patients treated with thyroid hormone products. These include urticaria, pruritus, skin rash, flushing, angioedema, various gastrointestinal symptoms (abdominal pain, nausea, vomiting and diarrhea), fever, arthralgia, serum sickness, and wheezing. Hypersensitivity to levothyroxine itself is not known to occur.
5.1 Cardiac Adverse Reactions in the Elderly and in Patients with Underlying Cardiovascular Disease
Over-treatment with levothyroxine may cause an increase in heart rate, cardiac wall thickness, and cardiac contractility and may precipitate angina or arrhythmias, particularly in patients with cardiovascular disease and in elderly patients. Initiate SYNTHROID therapy in this population at lower doses than those recommended in younger individuals or in patients without cardiac disease.
Monitor for cardiac arrhythmias during surgical procedures in patients with coronary artery disease receiving suppressive SYNTHROID therapy. Monitor patients receiving concomitant SYNTHROID and sympathomimetic agents for signs and symptoms of coronary insufficiency.
If cardiac symptoms develop or worsen, reduce the SYNTHROID dose or withhold for one week and restart at a lower dose.
5.2 Myxedema Coma
Myxedema coma is a life-threatening emergency characterized by poor circulation and hypometabolism, and may result in unpredictable absorption of levothyroxine sodium from the gastrointestinal tract. Use of oral thyroid hormone drug products is not recommended to treat myxedema coma. Administer thyroid hormone products formulated for intravenous administration to treat myxedema coma.
5.3 Acute Adrenal Crisis in Patients with Concomitant Adrenal Insufficiency
Thyroid hormone increases metabolic clearance of glucocorticoids. Initiation of thyroid hormone therapy prior to initiating glucocorticoid therapy may precipitate an acute adrenal crisis in patients with adrenal insufficiency. Treat patients with adrenal insufficiency with replacement glucocorticoids prior to initiating treatment with SYNTHROID.
5.4 Prevention of Hyperthyroidism or Incomplete Treatment of Hypothyroidism
SYNTHROID has a narrow therapeutic index. Over- or undertreatment with SYNTHROID may have negative effects on growth and development, cardiovascular function, bone metabolism, reproductive function, cognitive function, emotional state, gastrointestinal function, and glucose and lipid metabolism. Titrate the dose of SYNTHROID carefully and monitor response to titration to avoid these effects [see Dosage and Administration (2.4)]. Monitor for the presence of drug or food interactions when using SYNTHROID and adjust the dose as necessary.
5.5 Worsening of Diabetic Control
Addition of levothyroxine therapy in patients with diabetes mellitus may worsen glycemic control and result in increased antidiabetic agent or insulin requirements. Carefully monitor glycemic control after starting, changing, or discontinuing SYNTHROID.
5.6 Decreased Bone Mineral Density Associated with Thyroid Hormone Over-Replacement
Increased bone resorption and decreased bone mineral density may occur as a result of levothyroxine over-replacement, particularly in post-menopausal women. 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. Administer the minimum dose of SYNTHROID that achieves the desired clinical and biochemical response to mitigate this risk.
The signs and symptoms of overdosage are those of hyperthyroidism and Adverse Reactions (6)]. In addition, confusion and disorientation may occur. Cerebral embolism, shock, coma, and death have been reported. Seizures occurred in a 3-year-old child ingesting 3.6 mg of levothyroxine. Symptoms may not necessarily be evident or may not appear until several days after ingestion of levothyroxine sodium.
Reduce the SYNTHROID dose or discontinue temporarily if signs or symptoms of overdosage occur. Initiate appropriate supportive treatment as dictated by the patient’s medical status.
For current information on the management of poisoning or overdosage, contact the National Poison Control Center at 1-800-222-1222 or www.poison.org.
SYNTHROID (levothyroxine sodium tablets, USP) contain synthetic crystalline L-3,3′,5,5′-tetraiodothyronine sodium salt [levothyroxine (T4) sodium]. Synthetic T4 is chemically identical to that produced in the human thyroid gland. Levothyroxine (T4) sodium has an empirical formula of C15H10I4N NaO4• H2O, molecular weight of 798.86 (anhydrous), and structural formula as shown:
SYNTHROID tablets for oral administration are supplied in the following strengths: 25 mcg, 50 mcg, 75 mcg, 88 mcg, 100 mcg, 112 mcg, 125 mcg, 137 mcg, 150 mcg, 175 mcg, 200 mcg, and 300 mcg. Each SYNTHROID tablet contains the inactive ingredients acacia, confectioner’s sugar (contains corn starch), lactose monohydrate, magnesium stearate, povidone, and talc. Each tablet strength meets USP Dissolution Test 3. Table 6 provides a listing of the color additives by tablet strength:
|Table 6. SYNTHROID Tablets Color Additives|
|25||FD&C Yellow No. 6 Aluminum Lakea|
|75||FD&C Red No. 40 Aluminum Lake, FD&C Blue No. 2 Aluminum Lake|
|88||FD&C Blue No. 1 Aluminum Lake, FD&C Yellow No. 6 Aluminum Lakea, D&C Yellow No. 10 Aluminum Lake|
|100||D&C Yellow No. 10 Aluminum Lake, FD&C Yellow No. 6 Aluminum Lakea|
|112||D&C Red No. 27 & 30 Aluminum Lake|
|125||FD&C Yellow No. 6 Aluminum Lakea, 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||FD&C Blue No. 1 Aluminum Lake, D&C Red No. 27 & 30 Aluminum Lake|
|200||FD&C Red No. 40 Aluminum Lake|
|300||D&C Yellow No. 10 Aluminum Lake, FD&C Yellow No. 6 Aluminum Lakea, FD&C Blue No. 1 Aluminum Lake|