PRECAUTIONS General Thyroid hormone therapy in patients with concomitant diabetes mellitus (see PRECAUTIONS–Drug Interactions, Insulin or Oral Hypoglycemics regarding interaction and dose adjustment with insulin) or insipidus or adrenal cortical insufficiency may aggravate the intensity of their symptoms. Appropriate adjustments of the various therapeutic measures directed at these concomitant endocrine diseases are required. The therapy of myxedema coma requires simultaneous administration of glucocorticoids. (See PRECAUTIONS–Adjunctive Therapy ). Hypothyroidism decreases and hyperthyroidism increases the sensitivity to anticoagulants. Prothrombin time should be closely monitored in thyroid-treated patients on anticoagulants and dosage of the latter agents adjusted on the basis of frequent prothrombin time determinations. Oral therapy should be resumed as soon as the clinical situation has been stabilized and the patient is able to take oral medication. If L-thyroxine rather than liothyronine sodium is used in initiating oral therapy, the physician should bear in mind that there is a delay of several days in the onset of L-thyroxine activity and that intravenous therapy should be discontinued gradually. Adjunctive Therapy Many investigators recommend that corticosteroids be administered routinely in the initial emergency treatment of all patients with myxedema coma. Patients with pituitary myxedema should receive adrenocortical hormone replacement therapy at or before the start of Triostat therapy. Similarly, patients with primary myxedema may also require adrenocortical hormone replacement therapy since a rapid return to normal body metabolism from a severely hypothyroid state may result in acute adrenocortical insufficiency and shock. In considering the need to elevate blood pressure, it should be kept in mind that tissue metabolic requirements are markedly reduced in the hypothyroid patient. Because arrhythmias and circulatory collapse have infrequently occurred following the concomitant administration of thyroid hormones and vasopressor therapies, use caution when administering these therapies concomitantly. (See PRECAUTIONS–Drug Interactions, Vasopressors .) Hyponatremia is frequently present in myxedema coma, but usually resolves without specific therapy as the metabolic status of the patient is improved with thyroid hormone treatment. Fluid therapy should be administered with great care to prevent cardiac decompensation. In addition, some patients with myxedema have inappropriate secretion of ADH and are susceptible to water intoxication. In some patients, respiratory depression has been a significant factor in the development or persistence of the comatose state. Decreased oxygen saturation and elevated CO2 levels respond quickly to artificial respiration. Infection is often present in myxedema coma and should be looked for and treated appropriately. Concomitant use of Triostat and artificial rewarming of patients is contraindicated. Although patients in myxedema coma are often hypothermic, most investigators believe that artificial rewarming is of little value or may be harmful. The peripheral vasodilation produced by external heat serves to further decrease circulation to vital internal organs and to increase shock if present. It has been reported that the administration of liothyronine sodium will restore a normal body temperature in 24 to 48 hours if heat loss is prevented by keeping the patient covered with blankets in a warm room. Laboratory Tests Treatment of patients with thyroid hormones requires the periodic assessment of thyroid status by means of appropriate laboratory tests besides the full clinical evaluation. Serum T3 and TSH levels should be monitored to assess dosage adequacy and biologic effectiveness. Drug Interactions Oral Anticoagulants Thyroid hormones appear to increase catabolism of vitamin K-dependent clotting factors. If oral anticoagulants are also being given, compensatory increases in clotting factor synthesis are impaired. Patients stabilized on oral anticoagulants who are found to require thyroid replacement therapy should be watched very closely when thyroid is started. If a patient is truly hypothyroid, it is likely that a reduction in anticoagulant dosage will be required. No special precautions appear to be necessary when oral anticoagulant therapy is begun in a patient already stabilized on maintenance thyroid replacement therapy. Insulin or Oral Hypoglycemics Initiating thyroid replacement therapy may cause increases in insulin or oral hypoglycemic requirements. The effects seen are poorly understood and depend upon a variety of factors such as dose and type of thyroid preparations and endocrine status of the patient. Patients receiving insulin or oral hypoglycemics should be closely watched during initiation of thyroid replacement therapy. Estrogen, Oral Contraceptives Estrogens tend to increase serum thyroxine-binding globulin (TBG). In a patient with a nonfunctioning thyroid gland who is receiving thyroid replacement therapy, free levothyroxine may be decreased when estrogens are started thus increasing thyroid requirements. However, if the patient's thyroid gland has sufficient function, the decreased free thyroxine will result in a compensatory increase in thyroxine output by the thyroid. Therefore, patients without a functioning thyroid gland who are on thyroid replacement therapy may need to increase their thyroid dose if estrogens or estrogen-containing oral contraceptives are given. Tricyclic Antidepressants Use of thyroid products with imipramine and other tricyclic antidepressants may increase receptor sensitivity and enhance antidepressant activity; transient cardiac arrhythmias have been observed. Thyroid hormone activity may also be enhanced. Digitalis Thyroid preparations may potentiate the toxic effects of digitalis. Thyroid hormonal replacement increases metabolic rate, which requires an increase in digitalis dosage. Ketamine When administered to patients on a thyroid preparation, this parenteral anesthetic may cause hypertension and tachycardia. Use with caution and be prepared to treat hypertension, if necessary. Vasopressors Thyroid hormones increase the adrenergic effect of catecholamines such as epinephrine and norepinephrine. Therefore, use of vasopressors in patients receiving thyroid hormone preparations may increase the risk of precipitating coronary insufficiency, especially in patients with coronary artery disease. Therefore, use caution when administering vasopressors with liothyronine (T3). Drug/Laboratory Test Interactions The following drugs or moieties are known to interfere with laboratory tests performed in patients on thyroid hormone therapy: androgens, corticosteroids, estrogens, oral contraceptives containing estrogens, iodine-containing preparations and the numerous preparations containing salicylates. Changes in TBG concentration should be taken into consideration in the interpretation of T4 and T3 values. In such cases, the unbound (free) hormone should be measured. Pregnancy, estrogens and estrogen-containing oral contraceptives increase TBG concentrations. TBG may also be increased during infectious hepatitis. Decreases in TBG concentrations are observed in nephrosis, acromegaly and after androgen or corticosteroid therapy. Familial hyper- or hypothyroxine-binding globulinemias have been described. The incidence of TBG deficiency approximates 1 in 9000. The binding of thyroxine by thyroxine-binding prealbumin (TBPA) is inhibited by salicylates. Medicinal or dietary iodine interferes with all in vivo tests of radioiodine uptake, producing low uptakes which may not be reflective of a true decrease in hormone synthesis. Carcinogenesis, Mutagenesis and Impairment of Fertility A reportedly apparent association between prolonged thyroid therapy and breast cancer has not been confirmed and patients on thyroid for established indications should not discontinue therapy. No confirmatory long-term studies in animals have been performed to evaluate carcinogenic potential, mutagenicity, or impairment of fertility in either males or females. Pregnancy Pregnancy Category A: Thyroid hormones do not readily cross the placental barrier. The clinical experience to date does not indicate any adverse effect on fetuses when thyroid hormones are administered to pregnant women. On the basis of current knowledge, thyroid replacement therapy to hypothyroid women should not be discontinued during pregnancy. Nursing Mothers Minimal amounts of thyroid hormones are excreted in human milk. Thyroid hormones are not associated with serious adverse reactions and do not have a known tumorigenic potential. However, caution should be exercised when thyroid hormones are administered to a nursing woman. Geriatric Use Clinical studies of liothyronine sodium did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function. Pediatric Use There is limited experience with Triostat in the pediatric population. Safety and effectiveness in pediatric patients have not been established.