Thyrolar

Name: Thyrolar

Precautions While Using Thyrolar

It is very important that your doctor check your progress at regular visits. This will allow your doctor to see if the medicine is working properly and to decide if you should continue to take it. Blood and urine tests will be needed to check for unwanted effects .

Liotrix should not be used for the treatment of obesity or for the purpose of losing weight. This medicine is ineffective for weight reduction and when taken in larger amount, it may cause more serious medical conditions .

Hypothyroidism can sometimes cause infertility in men and women. Liotrix should not be used for the treatment of infertility unless it is caused by hypothyroidism .

Call your doctor right away if you start to have chest pain, fast or irregular heartbeat, excessive sweating, heat intolerance, nervousness, or any other unusual medical condition .

For patients with diabetes, it is very important that you keep track of your blood or urine sugar levels as instructed by your doctor. Check with your doctor immediately if you notice any changes in your sugar levels .

A temporary loss of hair may occur during the first few months of liotrix therapy. Ask your doctor about this if you have any concerns .

Uses of Thyrolar

  • It is used to add thyroid hormone to the body.
  • It is used to treat or prevent an enlarged thyroid gland.
  • It is used to manage thyroid cancer.
  • It may be given to you for other reasons. Talk with the doctor.

How is this medicine (Thyrolar) best taken?

Use Thyrolar as ordered by your doctor. Read all information given to you. Follow all instructions closely.

  • Take on an empty stomach before breakfast.
  • Do not take colesevelam, colestipol, or cholestyramine within 4 hours of this medicine.
  • It may take several weeks to see the full effects.
  • Keep taking Thyrolar as you have been told by your doctor or other health care provider, even if you feel well.

What do I do if I miss a dose?

  • Take a missed dose as soon as you think about it.
  • If it is close to the time for your next dose, skip the missed dose and go back to your normal time.
  • Do not take 2 doses at the same time or extra doses.

Precautions

GeneralThyroid hormones should be used with great caution in a number of circumstances where the integrity of the cardiovascular system, particularly the coronary arteries, is suspected. These include patients with angina pectoris or the elderly, in whom there is a greater likelihood of occult cardiac disease. In these patients therapy should be initiated with low doses, i.e., one tablet of Thyrolar ½ or Thyrolar ¼. When, in such patients, a euthyroid state can only be reached at the expense of an aggravation of the cardiovascular disease, thyroid hormone dosage should be reduced.

Thyroid hormone therapy in patients with concomitant diabetes mellitus or diabetes insipidus or adrenal cortical insufficiency aggravates 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 DOSAGE AND ADMINISTRATION).

Hypothyroidism decreases and hyperthyroidism increases the sensitivity to oral anticoagulants. Prothrombin time should be closely monitored in thyroid treated patients on oral anticoagulants and dosage of the latter agents adjusted on the basis of frequent prothrombin time determinations. In infants, excessive doses of thyroid hormone preparations may produce craniosynostosis.

Information for the PatientPatients on thyroid hormone preparations and parents of children on thyroid therapy should be informed that:

  1. Replacement therapy is to be taken essentially for life, with the exception of cases of transient hypothyroidism, usually associated with thyroiditis, and in those patients receiving a therapeutic trial of the drug.
  2. They should immediately report during the course of therapy any signs or symptoms of thyroid hormone toxicity, e.g., chest pain, increased pulse rate, palpitations, excessive sweating, heat intolerance, nervousness, or any other unusual event.
  3. In case of concomitant diabetes mellitus, the daily dosage of antidiabetic medication may need readjustment as thyroid hormone replacement is achieved. If thyroid medication is stopped, a downward readjustment of the dosage of insulin or oral hypoglycemic agent may be necessary to avoid hypoglycemia. At all times, close monitoring of urinary glucose levels is mandatory in such patients.
  4. In case of concomitant oral anticoagulant therapy, the prothrombin time should be measured frequently to determine if the dosage of oral anticoagulants is to be readjusted.
  5. Partial loss of hair may be experienced by children in the first few months of thyroid therapy, but this is usually a transient phenomenon and later recovery is usually the rule.
  6. Tablets should be stored at cold temperature, between 36°F and 46°F (2°C and 8°C) in a tight, light-resistant container.

Laboratory TestsTreatment of patients with thyroid hormones requires the periodic assessment of thyroid status by means of appropriate laboratory tests besides the full clinical evaluation. The TSH suppression test can be used to test the effectiveness of any thyroid preparation bearing in mind the relative insensitivity of the infant pituitary to the negative feedback effect of thyroid hormones. Serum T4 levels can be used to test the effectiveness of all thyroid medications except T3. When the total serum T4 is low but TSH is normal, a test specific to assess unbound (free) T4 levels is warranted. Specific measurements of T4 and T3 by competitive protein binding or radioimmunoassay are not influenced by blood levels of organic or inorganic iodine.

Drug InteractionsOral AnticoagulantsThyroid 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 HypoglycemicsInitiating 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.

Cholestyramine or ColestipolCholestyramine or colestipol binds both T4 and T3 in the intestine thus impairing absorption of these thyroid hormones. In vitro studies indicate that the binding is not easily removed. Therefore, four to five hours should elapse between administration of cholestyramine or colestipol and thyroid hormones.

Estrogen, Oral ContraceptivesEstrogens 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.

Drug/Laboratory Test InteractionsThe 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.

  1. 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 9,000. The binding of thyroxine by TBPA is inhibited by salicylates.
  2. Medicinal or dietary iodine interferes with all in vivo tests of radio-iodine uptake, producing low uptakes which may not be relative of a true decrease in hormone synthesis.
  3. The persistence of clinical and laboratory evidence of hypothyroidism in spite of adequate dosage replacement indicates either poor patient compliance, poor absorption, excessive fecal loss, or inactivity of the preparation. Intracellular resistance to thyroid hormone is quite rare.

Carcinogenesis, Mutagenesis, and Impairment of FertilityA 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-Category AThyroid 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 MothersMinimal amounts of thyroid hormones are excreted in human milk. Thyroid is not associated with serious adverse reactions and does not have a known tumorigenic potential. However, caution should be exercised when thyroid is administered to a nursing woman.

Pediatric UsePregnant mothers provide little or no thyroid hormone to the fetus. The incidence of congenital hypothyroidism is relatively high (1:4000) and the hypothyroid fetus would not derive any benefit from the small amounts of hormone crossing the placental barrier. Routine determinations of serum (T4) and/or TSH is strongly advised in neonates in view of the deleterious effects of thyroid deficiency on growth and development.

Treatment should be initiated immediately upon diagnosis, and maintained for life, unless transient hypothyroidism is suspected; in which case, therapy may be interrupted for 2 to 8 weeks after the age of 3 years to reassess the condition. Cessation of therapy is justified in patients who have maintained a normal TSH during those 2 to 8 weeks.

Overdosage

Signs and SymptomsExcessive doses of thyroid result in a hypermetabolic state resembling in every respect the condition of endogenous origin. The condition may be self-induced.

Treatment of OverdosageDosage should be reduced or therapy temporarily discontinued if signs and symptoms of overdosage appear.

Treatment may be reinstituted at a lower dosage. In normal individuals, normal hypothalamic-pituitary-thyroid axis function is restored in 6 to 8 weeks after thyroid suppression.

Treatment of acute massive thyroid hormone overdosage is aimed at reducing gastrointestinal absorption of the drugs and counteracting central and peripheral effects, mainly those of increased sympathetic activity. Vomiting may be induced initially if further gastrointestinal absorption can reasonably be prevented and barring contraindications such as coma, convulsions, or loss of the gagging reflex. Treatment is symptomatic and supportive. Oxygen may be administered and ventilation maintained. Cardiac glycosides may be indicated if congestive heart failure develops. Measures to control fever, hypoglycemia, or fluid loss should be instituted if needed. Antiadrenergic agents, particularly propranolol, have been used advantageously in the treatment of increased sympathetic activity. Propranolol may be administered intravenously at a dosage of 1 to 3 mg over a 10 minute period or orally, 80 to 160 mg/day, initially, especially when no contraindications exist for its use.

Principal Display Panel

Rx Only NDC 0456-0040-01

Thyrolar® 1/4

(liotrix tablets, USP)

Store at cold temperature,

between 36°F and 46°F (2°C and 8°C)

In a tight, light-resistant container.

100 TABLETS

FOREST PHARMACEUTICALS, INC.
Subsidiary of Forest Laboratories, Inc.
St. Louis, MO 63045

Thyrolar Dosage and Administration

General

  • Initially, monitor response to therapy about every 6–8 weeks.e k Once normalization of thyroid function and serum TSH concentrations has been achieved, patients may be evaluated less frequently (i.e., every 6–12 months).e k However, if dosage is changed, measure serum TSH concentrations after 8–12 weeks.k

  • Natural and synthetic thyroid agent preparations are not necessarily directly comparable; however, the following equivalencies have been suggested based on clinical response:j

Equivalencies of Thyroid Preparations Based on Clinical Responsej

Thyroid Agent

Approximate Equivalent Dosage

Levothyroxine sodium

100 mcg or less

Liothyronine sodium

25 mcg

Liotrix (levothyroxine sodium/liothyronine sodium)

50 mcg/12.5 mcg (Thyrolar)

Thyroglobulin

65 mg

Thyroid

60–65 mg (1 grain)

Administration

Oral Administration

Administer orally, usually as a single daily dose before breakfast.a b

Dosage

Available as fixed-combination preparation containing levothyroxine sodium and liothyronine sodium; dosage expressed in terms of the salts of both drugs.a b

Current USP standards define liotrix as containing levothyroxine sodium and liothyronine sodium in a ratio of 4:1 by weight.a Thus, Thyrolar-1 contains 50 mcg of levothyroxine sodium and 12.5 mcg of liothyronine sodium, which is approximately equivalent to 60 mg of thyroid.a (See General under Dosage and Administration.)

Adjust dosage carefully according to clinical and laboratory response to treatment.a j Avoid undertreatment or overtreatment.j (See Therapy Monitoring under Cautions.)

Initiate at a lower dosage level in geriatric patients, in patients with functional or ECG evidence of cardiovascular disease, and in patients with severe, long-standing hypothyroidism or other endocrinopathies.a j

Pediatric Patients

Hypothyroidism Oral

Initiate therapy at full replacement dosages as soon as possible after diagnosis of congenital hypothyroidism to prevent deleterious effects on intellectual and physical growth and development.b h The following dosages have been recommended:a

Dosage for Management of Hypothyroidism in Pediatric Patientsab

Age

Daily T3/T4 Dosage

0–6 months

3.1/12.5–6.25/25 mcg

6–12 months

6.25/25–9.35/37.5 mcg

1–5 years

9.35/37.5–12.5/50 mcg

6–12 years

12.5/50–18.75/75 mcg

>12 years

>18.75/75 mcg

When transient hypothyroidism is suspected, therapy may be temporarily discontinued when the child is >3 years of age to reassess the condition.b j m (See Pediatric Use under Cautions.)

Adults

Hypothyroidism Oral

Usual initial dosage is one tablet of Thyrolar-1/2 daily.a b Increase by one tablet of Thyrolar-1/4 at intervals of 2–3 weeks.a b

For management of long-standing myxedema, particularly when cardiovascular impairment is suspected, usual initial dosage is one tablet of Thyrolar-1/4 daily.b

Usual maintenance dosage is one tablet of Thyrolar-1 to one tablet of Thyrolar-2 daily.a b Serum TSH and T4 concentrations usually return to normal after 2–3 weeks of therapy.a b Failure to respond adequately to one Thyrolar-3 tablet daily suggests presence of malabsorption or patient noncompliance.a b

Pituitary TSH Suppression Thyroid Cancer Oral

Administration of dosages higher than those used for replacement therapy usually is required to suppress TSH to low or undetectable concentrations.b Medullary carcinoma of the thyroid usually unresponsive to this therapy.b

Special Populations

Patients with Cardiovascular Disease

Hypothyroidism

Initiate therapy at lower dosages than those recommended for patients without cardiovascular disease.b j k

Usual initial dosage is one Thyrolar-1/4 tablet or one Thyrolar -1/2 tablet daily.b If angina appears or if cardiovascular disease is aggravated, reduce dosage or temporarily withhold therapy and then cautiously restart therapy at a lower dosage.b j

Geriatric Patients

Hypothyroidism

Initiate therapy at lower dosages than those recommended for younger patients.b j k

Usual initial dosage is one Thyrolar-1/4 tablet or one Thyrolar -1/2 tablet daily.b If cardiovascular disease is aggravated, reduce dosage or temporarily withhold therapy and then cautiously restart therapy at a lower dosage.b j

Thyrolar Pharmacokinetics

Absorption

Bioavailability

Levothyroxine (T4): Variably absorbed from the GI tract (range: 40–80%).b j Extent of absorption is increased in the fasting state and decreased in malabsorption states.b j

Liothyronine (T3): Almost completely absorbed from the GI tract (about 95%).b h j

Onset

Liothyronine has a more rapid onset of action than levothyroxine (24–72 hours versus 1–3 weeks).h i j

Distribution

Extent

T4 is distributed throughout most body tissues and fluids; highest concentrations found in liver and kidneys.j

Thyroid hormones do not readily cross the placenta;b j q however, some transfer does occur, as evidenced by levels in cord blood of athyrotic fetuses being approximately one-third maternal levels.q

Thyroid hormones are minimally distributed into breast milk.b j q

Plasma Protein Binding

Circulating thyroid hormones are >99% bound to serum proteins, including TBG, thyroxine-binding prealbumin (TBPA), and albumin.b j q T4 is more extensively and firmly bound to TBG and TBPA than T3.b j q Only unbound hormone is metabolically active.b q

Elimination

Metabolism

T4 and T3 are metabolized principally in the liver through sequential deiodination.b j q Approximately 80% of the daily dose of T4 is deiodinated to yield equal amounts of T3 and reverse T3 (rT3).j q T3 and rT3 are further deiodinated to diiodothyronine.j q Thyroid hormones are also metabolized via conjugation with glucuronides and sulfates and excreted directly into the bile and gut where they undergo enterohepatic recirculation.b j q

Elimination Route

Thyroid hormones are primarily eliminated by the kidneys.q A portion of the conjugated hormone reaches the colon unchanged and is eliminated in the feces.q Approximately 20% of T4 is eliminated in stool.q Urinary excretion of T4 decreases with age.q

Half-life

T4: Approximately 6–7 days.h i j

T3: Approximately 1–2 days.c h i j

These plasma half-lives are decreased in patients with hyperthyroidism and increased in those with hypothyroidism.h i j

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