Levothyroxine/Liothyronine Sodium Capsules
Levothyroxine/Liothyronine Sodium Capsules
25/5 mcg, 25/10 mcg, 50/5 mcg, 50/10 mcg, 75/5 mcg, 75/10 mcg, 9.5/2.25 mcg, 19/4.5 mcg, 28.5/6.8 mcg, 38/9 mcg, 76/18 mcg, 95/22.5 mcg, 114/27 mcg and 152/36 mcg
Levothyroxine (T4) is a synthetically prepared levo-isomer of thyroxine, a hormone secreted by the thyroid gland. Levothyroxine is used in the treatment of primary, secondary (pituitary), and tertiary (hypothalamic) hypothyroidism. Levothyroxine will potently suppress thyrotropin secretion in the management of goiter and chronic lymphocytic thyroiditis, and it can be used in combination with antithyroid agents to prevent the abc development of hypothyroidism or goitrogenesis during the treatment of thyrotoxicosis. Liothyronine (L-triiodothyronine or L-T3) is a synthetic sodium salt of the endogenous thyroid hormone triiodothyronine (T3). The oral medication is indicated for use as replacement or supplemental therapy in the treatment of hypothyroidism of any etiology, except transient hypothyroidism during the recovery phase of subacute thyroiditis; as a pituitary thyroid-stimulating hormone (TSH) suppressant in the treatment or prevention of various types of euthyroid goiters; and as a diagnostic agent in T3 suppression tests. Either form of liothyronine may be used for patients who are allergic to desiccated thyroid or thyroid extract derived from pork or beef. Liothyronine is potentially more cardiotoxic than levothyroxine. However, due to the faster onset of action and the need to peripherally convert levothyroxine (T4) to the biologically active T3, liothyronine has been recommended for treatment of myxedema coma. Levothyroxine is generally considered the most appropriate of the thyroid replacement agents for long-term treatment of hypothyroidism. However, a small randomized clinical trial demonstrated improvement in mood and neuropsychological function of hypothyroid patients with partial substitution of liothyronine for levothyroxine.3 Liothyronine received approval for use by the FDA in 1954.
Thyroid hormones increase the body's metabolic rate, enhancing oxygen consumption by most tissues of the body. They exert a profound effect on virtually every organ system in the body, being especially important in the development of the central nervous system. Liothyronine exhibits the actions of the biologically active form of the endogenous thyroid hormone, triiodothyronine. T3 is four times more active than T4, but lower serum levels are maintained. It is now well-established that 80% of circulating T3 results from peripheral conversion of T4, with the remainder secreted from the thyroid gland. Approximately 45% of T4 is converted to inactive reverse T3 (rT3) and 35% to 40% to biologically active T3. Iodothyronine 5'-deiodinase, the membrane bound enzyme responsible for extrathyroidal conversion, has the greatest activity in the liver and kidney. Enzymatic conversion also occurs through a PTU-insensitive 5'-deiodinase found primarily in the pituitary and central nervous system. Conversion may be inhibited during times of stress or illness, diverting T4 to the inactive reverse T3 (rT3). It seems that the binding of T3 to a nuclear thyroid hormone receptor initiates the majority of the effects produced in the tissues by thyroid hormones. Most synthetic and natural thyroid hormone analogs will bind to this protein, but T3 has a ten times greater receptor affinity than does T4. The release of T3 and T4 from the thyroid gland into the systemic circulation is regulated by TSH (thyrotropin), which is secreted by the anterior pituitary gland. Thyrotropin release is controlled by the secretion of thyroid-releasing hormone (TRH) from the hypothalamus and by a feedback mechanism dependent on the concentrations of circulating thyroid hormones. Because of this feedback mechanism, the administration of pharmacological doses of exogenous thyroid hormones, including liothyronine, to patients with normal thyroid function suppresses endogenous thyroid hormone secretion. Levothyroxine exhibits all the actions of endogenous thyroid hormone. Liothyronine (T3) is the principal hormone that exhibits these actions whereas levothyroxine (T4) is the major hormone secreted by the thyroid gland and is metabolically deiodinated to T3 in peripheral tissues. Serum concentrations of T4 and TSH are typically used as the primary monitoring parameters for determining thyroid function. Correction of hypothyroidism through administration of liothyronine or other thyroid hormones will increase cardiac consumption, resulting in increased cardiac output, ventricular contractility and heart rate with a decrease in total systemic vascular resistance. An increase in the rate and depth of respiration, vasodilation, motility of the gastrointestinal tract and an improved return to consciousness are also produced. Thyroid hormones increase the metabolic rate, which corrects hypothermia, by enhancing protein and carbohydrate metabolism, increasing gluconeogenesis, facilitating the mobilization of glycogen stores, and increasing protein synthesis. The number and activity of mitochondria in almost all cells of the body is increased. In primary hypothyroidism, thyroid stimulating hormone (TSH) levels should correct when normal levels of thyroid hormone are established.
Oral aluminum hydroxide, magnesium salts, calcium salts, calcium carbonate, and antacids, containing any of these electrolyte salts have been reported to chelate oral levothyroxine within the GI tract when administered simultaneously, leading to decreased absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of levothyroxine with oral calcium supplements and aluminum hydroxide. This interaction may also occur with liothyronine. To be prudent and to minimize this interaction, administer liothyronine at least 4 hours before or after antacids or other drugs containing aluminum, magnesium, or calcium.91213 Polysaccharide-iron complex and other oral iron salts have been reported to chelate oral thyroid hormones within the GI tract when administered simultaneously, leading to decreased thyroid hormone absorption. Some case reports have described clinical hypothyroidism resulting from coadministration of thyroid hormones with oral iron supplements.14 To minimize the risk of interaction, oral thyroid hormones should be administered at least 4 hours before or after the ingestion of iron supplements.9 Cholestyramine can bind T3 and T4 in the gastrointestinal tract, impairing absorption of both hormones.8 Colestipol may have similar effects on absorption. Other cholesterol-lowering agents might also interfere with thyroid absorption.15 At least 4—6 hours should be allowed between the administration of thyroid hormones and either cholestyramine or colestipol. Administration of thyroid hormones with sucralfate16 may result in a decreased bioavailability of liothyronine. The exact mechanism of this interaction is not known, but the agents should be separated in administration. Cation exchange resins like sodium polystyrene sulfonate (i.e., Kayexalate), can bind thyroid hormones in the GI tract and inhibit thyroid hormone absorption.9 Administer liothyronine at least 4 hours apart from cation exchange resins.
Liothyronine is contraindicated for use in patients with untreated thyrotoxicosis of any etiology. Use caution when administering liothyronine to patients with autonomous thyroid tissue to prevent precipitation of thyrotoxicosis. Liothyronine is contraindicated for use in patients with diagnosed but untreated adrenal insufficiency. Adrenal insufficiency should be corrected prior to or during concomitant administration of thyroid agents. Administration of thyroid hormones to patients with uncontrolled adrenal insufficiency can cause adrenal crisis due to an increase in the body's demand for adrenal hormones. Symptoms of adrenal insufficiency can be unmasked or exacerbated by the administration of thyroid agents. Supplemental adrenocortical steroids may be necessary to meet the body's increased demand for adrenal hormones.Liothyronine is known to be substantially excreted by the kidney, and the risk of toxic reactions may be greater in patients with renal impairment or renal failure. Care should be taken in dosage selection for these patients; lower initial dosages and slower titration may be needed. Secondary causes of hypothyroidism (e.g., morphologic hypogonadism and nephroses) should be ruled out prior to beginning treatment with liothyronine. Patients with hypothyroidism secondary to hypopituitarism are likely to have suppressed adrenal function as well, which should be corrected prior to initiating thyroid replacement therapy. Symptoms of hypopituitarism can be unmasked or exacerbated by the administration of thyroid hormones. Caution should be used in geriatric patients since they may be more sensitive to the cardiac effects of thyroid replacement with liothyronine, and are more likely to have concomitant diseases or drug therapy. Lower initial dosages and slower titration are recommended. Individualize dosage.
Levothyroxine and Liothyronine are classified in FDA pregnancy risk category A. Thyroid hormones undergo minimal placental transfer and human experience does not indicate adverse fetal effects; do not discontinue needed replacement during pregnancy.6 Also, hypothyroidism that is diagnosed during pregnancy should be promptly treated. Measure TSH during each trimester to gauge adequacy of thyroid replacement dosage since during pregnancy thyroid requirements may increase. Immediately after obstetric delivery, dosage should return to the pre-pregnancy dose, monitor thyroid function tests 6—8 weeks postpartum to assess for needed adjustments.
Thyroid hormones, like levothyroxine and liothyronine, are generally compatible with breast-feeding; minimal amounts of thyroid hormones are excreted in breast milk.7 Thyroid hormones do not have a known tumorigenic potential and are not associated with serious adverse reactions in nursing infants. However, use caution when administering liothyronine to a nursing woman 6; changes in thyroid status in the post-partum period may require careful monitoring and maternal dosage adjustment. It should be noted that in general, adequate thyroid status is needed to maintain normal lactation, and there is no reason maternal replacement should be halted due to lactation alone. Levothyroxine is often the preferential drug to treat hypothyroidism and is considered compatible with breastfeeding
Some possible side effects include: changes in appetite; changes in menstrual periods; diarrhea; hair loss; headache; trouble sleeping; weight loss. Monitor for signs and symptoms of hypothyroidism that could require an upward adjustment of the liothyronine dosage. Signs or symptoms of underdosage or hypothyroidism include constipation, cold intolerance, dry skin (xerosis) or hair, fatigue, impaired intellectual performance or other mental status changes (e.g., depression), deepening of voice, lethargy, weight gain, tongue enlargement, and, eventually, myxedema coma. Transient partial alopecia may occur in children in the first few months of treatment, but normal hair growth usually recovers.6 Alopecia may be due to hyperthyroidism from therapeutic overdosage or to hypothyroidism from therapeutic underdosage.35 Many of the signs and symptoms of thyroid hormone imbalance are subtle and insidious. Manifestations of liothyronine excessive dosage or hyperthyroidism include anorexia, diaphoresis, diarrhea, dyspnea, elevated hepatic enzymes, emotional lability, fatigue, fever, flushing, headache, heat intolerance, hyperthyroidism, appetite stimulation, infertility, irritability, insomnia, menstrual irregularity (e.g., amenorrhea), muscle weakness, muscle cramps, nausea, vomiting, nervousness or anxiety, tremor, and weight loss. Long-term use of thyroid hormones, like liothyronine, has been associated with decreased bone mineral density, particularly in postmenopausal females on greater than replacement doses or in any women receiving suppressive doses.
Store this medication at 68°F to 77°F (20°C to 25°C) and away from heat, moisture and light. Keep all medicine out of the reach of children. Throw away any unused medicine after the beyond use date. Do not flush unused medications or pour down a sink or drain.