Thyroid Hormones (Systemic)

This monograph includes information on the following:

1) Levothyroxine
2) Liothyronine
3) Liotrix 
4) Thyroglobulin  * 
5) Thyroid

VA CLASSIFICATION
Levothyroxine
Primary: HS851
Secondary: AN500; DX900

Liothyronine
Primary: HS851
Secondary: AN500; DX900

Liotrix
Primary: HS851
Secondary: AN500

Thyroglobulin
Primary: HS851
Secondary: AN500

Thyroid
Primary: HS851
Secondary: AN500


Commonly used brand name(s): Armour Thyroid5; Cytomel2; Eltroxin1; Levo-T1; Levothroid1; Levoxyl1; PMS-Levothyroxine Sodium1; Synthroid1; Thyrar5; Thyroid Strong5; Triostat®2; Westhroid5.

Another commonly used name for Levothyroxine is
L-Thyroxine .
Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

*Not commercially available in the U.S.

Not commercially available in Canada.



Category:


Thyroid hormone—Levothyroxine; Liothyronine; Liotrix; Thyroglobulin; Thyroid;

Antineoplastic—Levothyroxine; Liothyronine; Liotrix; Thyroglobulin; Thyroid;

Diagnostic aid (thyroid function)—Levothyroxine; Liothyronine;

Indications

Accepted

Hypothyroidism (diagnosis and treatment)—Thyroid hormones are indicated as replacement therapy in the treatment of thyroid hormone deficiency (hypothyroidism) of any etiology (except transient hypothyroidism during the recovery phase of subacute thyroiditis), as well as for simple (nonendemic) goiter and chronic lymphocytic (Hashimoto's) thyroiditis1 {11} {12} {13}.
—In general, levothyroxine is the preferred thyroid hormone for use in the treatment of hypothyroidism because of the absence of variability and the ease of monitoring of plasma concentrations; it is the drug of choice in the treatment of congenital hypothyroidism. Liothyronine is recommended by some clinicians because of its short half-life and readily reversible effects for initial therapy in myxedema and myxedema coma, as well as for hypothyroid patients who also have heart disease, although there are significant risks associated with the latter use. Liothyronine may also be preferred during preparation for radioisotope scanning procedures or when gastrointestinal absorption processes are impaired. Disadvantages of thyroid extract and thyroglobulin tablets are their variable potencies and the fact that triiodothyronine (T 3) and thyroxine (T 4) concentrations fluctuate and cannot be used to regulate dosage. Liotrix is no longer considered advantageous because of the natural conversion of T 4 to T 3 in the tissues.

Goiter (prophylaxis1 and treatment)—Thyroid hormones are indicated to suppress the growth of some {05} adenomatous goiters, and to prevent the goitrogenic effects of other medications such as lithium, aminosalicylic acid, and some sulfonamide compounds {13}.

Carcinoma, thyroid (prophylaxis and treatment)1—Thyroid hormones are indicated in the treatment of thyrotropin-dependent thyroid gland carcinoma {13}. Some clinicians believe that prophylactic administration of thyroid hormones after neck irradiation will prevent development of thyroid gland carcinoma.

Thyroid function studies—Levothyroxine1and liothyronine are indicated as diagnostic aids (for example, the T 3 suppression test), although this use has generally been replaced by other tests {08} {13}.

Unaccepted
Use of thyroid hormones to treat vague symptoms such as dry skin, fatigue, constipation, abnormalities of reproductive function, growth retardation, or obesity without laboratory confirmation of contributing hypothyroidism is inappropriate and may cause hyperthyroidism in euthyroid individuals.

1 Not included in Canadian product labeling.



Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Source—
    Natural products include thyroglobulin and thyroid.
    Synthetic products include levothyroxine, liothyronine, and liotrix.


Composition
    Levothyroxine: T 4 (thyroxine), with approximately 30% being converted to T 3 in peripheral tissues.
    Liothyronine: T 3 (triiodothyronine).
    Liotrix, thyroglobulin, and thyroid: T 3 and T 4.
Molecular weight—
    Levothyroxine sodium: 798.86 (anhydrous)
    Liothyronine sodium: 672.96


Equivalent strength (approximate), based on clinical response
    Levothyroxine: 100 mcg (0.1 mg) or less.

    Liothyronine: 25 mcg (0.025 mg).



Liotrix
     Levothyroxine and liothyronine: 60 mcg (0.06 mg) and 15 mcg (0.015 mg), or 50 mcg (0.05 mg) and 12.5 mcg (0.0125 mg), respectively.

    Thyroglobulin: 60 mg.

     Thyroid USP: 60 mg.


Note: Because of the difficulty in measuring actual hormonal content of thyroglobulin and Thyroid USP, the measurable amounts of levothyroxine and liothyronine in these preparations may be less than the clinical equivalent. However, for purposes of dosage adjustment, the above equivalent strengths are appropriate.


Mechanism of action/Effect:

The action of thyroid hormones is not completely understood, but they have both catabolic (calorigenic) and anabolic effects and are therefore involved in normal metabolism, growth, and development, especially the development of the central nervous system (CNS) of infants. A feedback system involving the hypothalamus, anterior pituitary, and thyroid normally regulates circulating thyroid hormone concentrations.

Absorption:


Oral:

Levothyroxine: Incomplete and variable, especially when taken with food; average 50 to 75% {13}.

Liothyronine: Approximately 95% {08}.

Note: Absorption may be reduced in patients with congestive heart failure, malabsorption syndromes, or diarrhea {13}.



Protein binding:

Very high (more than 99%), but not firmly bound {01} {08} {13}.

Biotransformation:

As for endogenous thyroid hormone; levothyroxine (approximately 30% {09}) is deiodinated in peripheral tissues; small amounts are metabolized in the liver and excreted in bile.

Half-life:


Levothyroxine:

Euthyroid: 6 to 7 days.

Hypothyroid: 9 to 10 days.

Hyperthyroid: 3 to 4 days.



Liothyronine:

Euthyroid: 1 day.

Hypothyroid: 1.4 days.

Hyperthyroid: 0.6 day.


Note: Because thyroid and thyroglobulin contain varying amounts of thyroxine and triiodothyronine, their half-lives will vary but will be somewhere between that for T 4 and T 3.


Time to peak therapeutic effect


With chronic stable oral dosing:

Levothyroxine, thyroglobulin, thyroid: 3 to 4 weeks.

Liothyronine: 48 to 72 hours {01}.


Duration of therapeutic action


After withdrawal of chronic therapy:

Levothyroxine, thyroglobulin, thyroid: 1 to 3 weeks.

Liothyronine: Up to 72 hours.



Precautions to Consider

Note: The following precautions apply to patients with abnormal thyroid status (hypothyroidism or, in some cases, hyperthyroidism). Patients in stable euthyroid condition as a result of continuing thyroid hormone therapy may be expected to respond in the same way as individuals with normal thyroid function and, therefore, the following precautions (except for Patient monitoring) do not usually apply in those circumstances.


Carcinogenicity/Mutagenicity

Studies have not been done in animals. A reported association with breast cancer has not been confirmed and does not justify withholding thyroid hormone treatment.

Pregnancy/Reproduction

Pregnancy—
Thyroid hormones cross the placenta, but only to a limited extent. However, clinical experience in humans has not shown that appropriate use of thyroid hormones causes adverse effects in the fetus. Monitoring of maternal dose is important as maternal dose requirements may change during pregnancy. Intra-amniotic levothyroxine has been used to treat fetal hypothyroidism.

FDA Pregnancy Category A.

Breast-feeding

Problems in humans have not been documented with appropriate use of thyroid hormones in women who are breast-feeding. Minimal amounts of exogenous thyroid hormones are distributed into breast milk.

Pediatrics

Studies performed to date have not demonstrated pediatrics-specific problems that would limit the usefulness of thyroid hormones in children. However, caution is necessary in interpreting results of thyroid function tests in neonates, because serum T 4 concentrations are transiently elevated and serum T 3 concentrations are transiently low, and the infant pituitary is relatively insensitive to the negative feedback effect of thyroid hormones.


Geriatrics


The elderly may be more sensitive to the effects of thyroid hormones. Thyroid hormone replacement requirements are about 25% lower in some patients over the age of 60 years than in younger adults; therefore, individualization of dose is recommended {08}.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.
In most cases, relative need for thyroid hormone dosage adjustment will depend on the thyroid state of the patient and the dosages of all medications involved. Dosage adjustment should be based on results of thyroid function tests and clinical status {03}.

» Anticoagulants, coumarin- or indandione-derivative    (the effects of the oral anticoagulant may be altered, depending on the thyroid status of the patient; an increase in dosage of thyroid hormone may necessitate a decrease in oral anticoagulant dosage; adjustment of oral anticoagulant dosage on the basis of prothrombin time is recommended)


Antidepressants, tricyclic    (concurrent use with thyroid hormones may increase the therapeutic and toxic effects of both drugs, possibly due to increased receptor sensitivity to catecholamines; toxic effects include cardiac arrhythmias and CNS stimulation; also the onset of action of tricyclics may be accelerated)


Antidiabetic agents, sulfonylurea or
Insulin    (thyroid hormones may increase {08} insulin or antidiabetic agent requirements; careful monitoring of diabetic control is recommended, especially when thyroid therapy is started, changed, or discontinued)


Beta-adrenergic blocking agents    (may decrease peripheral conversion of T 4 [thyroxine] to T 3 [triiodothyronine])


» Cholestyramine or
» Colestipol    (concurrent use may decrease the effects of thyroid hormones by binding and delaying or preventing absorption; an interval of 4 to 5 hours between administration of the two medications and regular monitoring of thyroid function tests are recommended)


Corticosteroids, glucocorticoid with mineralocorticoid activity or
Corticosteroids, mineralocorticoid or
Corticotropin (ACTH)    (changes in the thyroid status of the patient that may occur as a result of administration, changes in dosage, or discontinuation of thyroid hormones may necessitate adjustment of corticosteroid dosage because metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients)


Digitalis glycosides    (hypothyroid patients may have an increased risk for digitalis toxicity; thyroid hormone replacement therapy increases the metabolic rate, which may necessitate an increase in the digitalis dose{35})


Estrogens    (increase serum thyroxine-binding globulin; in patients with a nonfunctioning thyroid gland, thyroid hormone requirements may be increased)


Hepatic enzyme inducers (See Appendix II )    (increase hepatic degradation of levothyroxine, which may result in increased requirements; dosage adjustment may be necessary)

    (phenytoin also reduces serum protein binding of levothyroxine, and reduces total and free serum T 4 by 15 to 25%; despite this, most patients remain euthyroid and dosage of thyroid hormone does not need to be adjusted)


Ketamine    (concurrent use may produce marked hypertension and tachycardia; cautious administration to patients receiving thyroid hormone therapy is recommended )


Maprotiline    (concurrent use with thyroid hormones may enhance the possibility of cardiac arrhythmias; dosage adjustment may be necessary)


Sodium iodide I 123 or
Sodium iodide I 131 or
Sodium pertechnetate Tc 99m    (thyroid hormones may decrease the normal thyroidal uptake of I 123, I 131, or pertechnetate ion)


Somatrem or
Somatropin    (concurrent excessive use of thyroid hormones with somatrem or somatropin may accelerate epiphyseal closure. However, untreated hypothyroidism may interfere with growth response to somatrem or somatropin; prior and/or concurrent thyroid hormone replacement is recommended)


» Sympathomimetics    (concurrent use may increase the effects of these medications or thyroid hormone; thyroid hormones enhance risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease)


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Risk-benefit should be considered when the following medical problems exist
» Adrenocortical insufficiency    (must be corrected while thyroid replacement therapy is being given, to prevent precipitation of acute adrenocortical insufficiency)


» Cardiovascular disease, including angina pectoris, arteriosclerosis, coronary artery disease, hypertension, myocardial infarction    (because of the risks associated with overly rapid thyroid hormone replacement and increased metabolic demands; mobilization of myxedema fluid may produce pitting edema 1 to 3 or more weeks after a change in dosage)


Diabetes mellitus    (possible reduced glucose tolerance and increased insulin or oral antidiabetic agent requirements)


» Hyperthyroidism, history of    (residual autonomous thyroid function may be present after therapy for hyperthyroidism, necessitating lower than typical doses)


Malabsorption states, such as celiac disease    (absorption, especially of levothyroxine, is reduced; dosage adjustment may be necessary)


» Pituitary insufficiency    (associated adrenocortical insufficiency must be corrected before thyroid replacement therapy is initiated, to prevent precipitation of acute adrenocortical insufficiency)


Sensitivity to thyroid hormone
» Thyrotoxicosis being treated with antithyroid medication
» Caution is required also in patients with long-standing hypothyroidism or myxedema, who may be more sensitive to effects of thyroid hormones.

Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):


Note: In patients receiving levothyroxine, liotrix, or thyroid extract for primary hypothyroidism, serum free T 4 index (total serum T 4 and T 3 resin uptake) or serum free T 4 together with a serum thyroid-stimulating hormone (TSH) are the most useful tests for monitoring replacement therapy. Serum TSH measurements are not useful in hypothyroidism secondary to pituitary insufficiency. In the rare patient receiving liothyronine replacement, serum T 4 concentrations will remain low and normalization of serum TSH indicates that treatment is adequate. Overdosage with liothyronine can best be recognized by clinical symptoms of hyperthyroidism and/or by a decrease in serum TSH to subnormal levels.
Many medications affect the results of thyroid function tests and may produce false results.
Caution is necessary in interpreting results of thyroid function tests in neonates, because serum T 4 concentrations are transiently elevated and serum T 3 concentrations are transiently low, and the infant pituitary is relatively insensitive to the negative feedback effect of thyroid hormones.

The following have been found to be the most useful in general and may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):
» Free T 4 (thyroxine) index determinations or
Free (unbound) T 4 determinations     (recommended at periodic intervals in most patients)


Measurement of bone age and
» Measurement of growth and
» Measurement of psychomotor development    (recommended at periodic intervals in children with congenital hypothyroidism )


» Observation for signs of ischemia or tachyarrhythmias     (recommended in hypothyroid patients with cardiovascular disease to aid in adjustment of dosage and to prevent overdosage or overly rapid increase in dosage)


» TSH (thyroid-stimulating hormone) determinations and
» T 3 (triiodothyronine) or T 4 resin uptake determinations and
» Total serum T 4 determinations, by radioimmunoassay and
» Total serum T 3 determinations, by radioimmunoassay    (which thyroid function tests are most useful for a particular patient depends on the agent, condition being treated, other agents used concomitantly, and existing conditions that are capable of altering test results by altering serum thyroxine-binding globulin [TBG] concentrations)




Side/Adverse Effects

Note: Side/adverse effects are dose-related and the dose at which they occur varies with each patient; incidence may be reduced by slowly increasing the initial dose to the minimum effective dose.
Side/adverse effects may occur more rapidly with liothyronine than with levothyroxine or thyroid because of its rapid onset of action.
In infants, excessive doses may result in craniosynostosis.
Partial loss of hair may occur in children during the first few months of treatment; normal hair growth usually returns, even with continued treatment.

The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent or rare
    
Allergic reaction (skin rash or hives){35}
    
hyperthyroidism or overdosage {35}{35}(changes in appetite; changes in menstrual periods; chest pain; diarrhea; fast or irregular heartbeat; fever; hand tremors; headache; irritability ; leg cramps; nervousness; sensitivity to heat; shortness of breath; sweating; trouble in sleeping; vomiting ; weight loss)
    
pseudotumor cerebri, in children (severe headache)



Those indicating need for medical attention only if they continue or are bothersome
    
Hypothyroidism or underdosage (changes in menstrual periods ; clumsiness; coldness; constipation; dry, puffy skin; headache ; listlessness; muscle aches; sleepiness; tiredness; weakness; weight gain)





Overdose
For specific information on the agents used in the management of thyroid hormones overdose, see:    • Beta-adrenergic Blocking Agents (Systemic) monograph;
   • Charcoal, Activated (Oral-Local) monograph;
   • Hydrocortisone in Corticosteroids—Glucocorticoid Effects (Systemic) monograph; and/or
   • Digitalis Glycosides (Systemic) monograph.


For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses when appropriate)—not necessarily inclusive:
    
Changes in appetite
    
changes in menstrual periods {35}
    
chest pain {35}
    
diarrhea {35}
    
fast or irregular heartbeat {35}
    
fever
    
hand tremors
    
headache {35}
    
irritability {35}
    
leg cramps
    
nervousness {35}
    
sensitivity to heat
    
shortness of breath
    
sweating {35}
    
thyroid storm–like effects (confusion; fever; jaundice, mild ; mood swings; muscle wasting; psychosis; restlessness, extreme; weakness, marked)—following massive overdose{35}
    
trouble in sleeping
    
vomiting
    
weight loss


Treatment of overdose
If symptoms of hyperthyroidism occur, it is recommended that thyroid hormone therapy be withdrawn for 2 to 6 days (1 to 2 days {02} for liothyronine), then resumed at a lower dose.


To decrease absorption:
Acute massive overdose is treated by reducing gastrointestinal absorption, if possible, by means of vomiting, followed by emptying of the stomach and/or use of a charcoal instillation, which may be useful up to 3 to 4 hours after oral ingestion of toxic doses of thyroid hormones.



Specific treatment:
Cardiac glycosides if congestive heart failure develops {01}{35}.

Beta-adrenergic blocking agents such as propranolol for treatment of increased sympathetic activity.{35}

Intravenous hydrocortisone to partially inhibit conversion of T 4 to T 3 {02} {08}.



Supportive care:
Administration of oxygen.{35} Implementation of measures to control fever, hypoglycemia, or fluid loss.{35} Patients in whom intentional overdose is confirmed or suspected should be referred for psychiatric consultation.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Thyroid Hormones (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Allergy to thyroid hormones

Pregnancy—Crosses the placenta to a limited extent and has not caused problems in the fetus with appropriate doses; regular monitoring is necessary as maternal dose requirements may change during pregnancy





Breast-feeding—Small amounts are distributed into breast milk





Use in the elderly—Sensitivity to thyroid effects is greater in the elderly than in younger age groups and dose adjustment may be necessary
Other medications, especially cholestyramine, colestipol, coumarin- or indandione-derivative anticoagulants, or sympathomimetics
Other medical problems, especially adrenocortical insufficiency, cardiovascular disease, history of hyperthyroidism, pituitary insufficiency, thyroid sensitivity with long-standing hypothyroidism or myxedema, or thyrotoxicosis

Proper use of this medication
» Importance of not taking more or less medication than the amount prescribed; taking medication at the same time every day for consistent effect

» Possible need for lifelong therapy; checking with physician before discontinuing medication

» Proper dosing
Missed dose: Taking as soon as possible; not taking if almost time for next dose and not doubling doses; notifying physician if two or more doses in a row are missed

» Proper storage

Precautions while using this medication
» Importance of close monitoring by the physician

Caution with angina or coronary artery disease; heavy exercise or exertion may precipitate angina

» Caution if any kind of surgery (including dental surgery) or emergency treatment is required

Avoiding other medications unless prescribed by physician because of possible interference with effects of thyroid hormone


Side/adverse effects
Signs of potential side effects, especially allergic reaction, hyperthyroidism, and pseudotumor cerebri


General Dosing Information
Dosage must be adjusted to meet the individual requirements of each patient, on the basis of clinical response and results of thyroid function tests.

Levothyroxine is the preferred form of thyroid replacement therapy.

Patients who are more than mildly hypothyroid initially should be treated with less than a full replacement dose, with doses then being increased gradually over a period of weeks. Otherwise, nervousness and rapid heart rate may occur.

Thyroid hormone replacement therapy for congenital hypothyroidism should be initiated as soon as possible after birth to minimize impaired mental and physical development. Treatment after about 3 months of age may reverse many of the physical effects but not all of the mental effects of hypothyroidism. Treatment should be continued for life, unless transient hypothyroidism is suspected, in which case therapy may be withdrawn for 2 to 8 weeks after 3 years of age; if thyroid-stimulating hormone (TSH) and thyroxine (T 4) concentrations remain normal throughout the withdrawal period, treatment is no longer necessary.

Suppression of TSH to normal levels must not be used as the sole criterion of adequacy of dose in congenital hypothyroidism, since TSH concentrations may remain elevated despite adequate or even excessive doses of thyroid hormone. Maintenance of appropriate T 4 concentrations for age is a more accurate guideline during infancy and childhood.

In general, thyroid hormone therapy is begun at a low dose, which is increased gradually to obtain a euthyroid state, followed by the dose required to maintain the response. However, this is not necessary in neonates, in whom rapid replacement is important, and who may be started at the full replacement dose. Adverse effects such as hyperactivity in the older child may be lessened by utilizing a starting dose of one-fourth the full replacement dose, and increasing the dose by one-fourth weekly until the full replacement dose is reached.

Rapid replacement of thyroid hormone is associated with less risk in younger adults than in older ones.

In hypothyroid patients with adrenocortical insufficiency or panhypopituitarism, replacement therapy with thyroid hormones must be preceded by adequate amounts of corticosteroids to prevent precipitation of acute adrenocortical insufficiency by the increase in metabolism. Supplemental corticosteroids may also be necessary for patients with prolonged or severe hypothyroidism, including myxedema.

In hypothyroid patients with myxedema or cardiovascular disease, the initial dosage of thyroid hormones should be very small and must be increased very gradually to prevent precipitation of angina, coronary occlusion, or stroke. If cardiovascular reactions occur, a reduction in thyroid hormone dosage may be required. Although some clinicians prefer to use liothyronine in these patients because its effects disappear more rapidly after withdrawal, regulation of dosage is more difficult and its rapid onset of action may also produce adverse cardiac effects as a result of abrupt changes in metabolic demands.

If, after prolonged therapy (2 to 6 months), no response occurs with physiologic doses or a response occurs only with large doses of thyroid hormone, it is recommended that the diagnosis be reevaluated.

For treatment of myxedema coma
It has been recommended that corticosteroids be administered initially in the emergency treatment of all patients with myxedema coma.{35} Patients with pituitary myxedema should receive adrenocortical hormone replacement therapy prior to or when beginning therapy with liothyronine.{35} Similarly, patients with primary myxedema should receive adrenocortical hormone replacement therapy to prevent acute adrenocortical insufficiency and shock, which may occur following a rapid return to normal body metabolism from a hypothyroid state.{35}

Artificial rewarming is contraindicated in conjunction with administration of liothyronine in patients with myxedema coma. The external heat causes peripheral vasodilation that further decreases circulation to vital organs and increases shock if it is present. If heat loss is prevented by keeping the patient in a warm room covered with blankets, administration of liothyronine usually restores normal body temperature within 24 to 48 hours.{35}

LEVOTHYROXINE

Summary of Differences
Indications: Usual drug of choice. Advantage over thyroid and thyroglobulin is a predictable effect because of standard hormonal content.

Pharmacology/pharmacokinetics: Absorption after oral administration is incomplete and variable, especially when taken with food.

Precautions: Medical problems/contraindications—Absorption may be significantly reduced in patients with malabsorption states.


Oral Dosage Forms

LEVOTHYROXINE SODIUM TABLETS USP

Usual adult dose
Mild hypothyroidism
Initial: Oral, 50 mcg (0.05 mg) as a single daily dose, with increments of 25 to 50 mcg (0.025 to 0.05 mg) at two- to three-week intervals {10} until the desired result is obtained. {13}

Maintenance: Oral, 75 to 125 mcg (0.075 to 0.125 mg) per day (or 1.5 mcg per kg of body weight per day) as a single daily dose. A higher maintenance dose (up to 200 mcg per day) may be necessary in some patients (e.g., those with malabsorption) {08}.

Severe hypothyroidism
Initial: Oral, 12.5 to 25 mcg (0.0125 to 0.025 mg) as a single daily dose, with increments of 25 mcg (0.025 mg) at two- to three-week intervals {10} until the desired result is obtained.

Maintenance: Oral, 75 to 125 mcg (0.075 to 0.125 mg) per day (or 1.5 mcg per kg of body weight per day) as a single daily dose. A higher maintenance dose (up to 200 mcg per day) may be necessary in some patients (e.g., those with malabsorption) {08}.


Note: In the elderly and in patients with long-standing hypothyroidism, myxedematous infiltration, or cardiovascular dysfunction, the initial dose is usually 12.5 to 25 mcg (0.0125 to 0.025 mg) a day, and dosage is incremented at three- to four-week intervals {08} {10} {12}. In the elderly, the maintenance dose is usually about 75 mcg (0.075 mg) per day.


Usual adult prescribing limits
Failure to respond to a daily dose of 150 mcg (0.15 mg) or more may indicate erroneous diagnosis of hypothyroidism, malabsorption, or poor compliance.

Usual pediatric dose
Children less than 6 months of age—Oral, 5 to 6 mcg (0.005 to 0.006 mg) per kg of body weight per day {12} or 25 to 50 mcg (0.025 to 0.05 mg) per day as a single daily dose {13}.

Children 6 to 12 months of age—Oral, 5 to 6 mcg (0.005 to 0.006 mg) per kg of body weight per day {12} or 50 to 75 mcg (0.05 to 0.075 mg) per day as a single daily dose {13}.

Children 1 to 5 years of age—Oral, 3 to 5 mcg (0.003 to 0.005 mg) per kg of body weight per day {12} or 75 to 100 mcg (0.075 to 0.1 mg) per day as a single daily dose {13}.

Children 6 to 10 years of age—Oral, 4 to 5 mcg (0.004 to 0.005 mg) per kg of body weight per day {12} or 100 to 150 mcg (0.1 to 0.15 mg) per day as a single daily dose {13}.

Children over 10 years of age—Oral, 2 to 3 mcg (0.002 to 0.003 mg) per kg of body weight per day {12} as a single daily dose until the adult dose is reached (usually 150 mcg [0.15 mg] per day) up to 200 mcg (0.2 mg) per day.

Note: Premature infants weighing less than 2000 grams, or infants at risk for cardiac failure receive a starting dose of 25 mcg (0.025 mg) a day which may be increased to 50 mcg (0.05 mg) a day in four to six weeks.


Usual geriatric dose
See Usual adult dose.

Strength(s) usually available
U.S.—


25 mcg (0.025 mg) (Rx) [Levo-T (scored){23}] [Levothroid] [Levoxyl{12}{32}{33}] [Synthroid (scored){22}][Generic]{25}


50 mcg (0.05 mg) (Rx) [Levo-T (scored){23}] [Levothroid] [Levoxyl{12}{32}{33}] [Synthroid (scored){22}][Generic]{25}


75 mcg (0.075 mg) (Rx) [Levo-T (scored){23}] [Levothroid] [Levoxyl{12}{32}{33}] [Synthroid (scored){22}][Generic]{25}


88 mcg (0.088 mg) (Rx) [Levothroid{24}] [Levoxyl{12}{32}{33}] [Synthroid (scored){13}{22}]


100 mcg (0.1 mg) (Rx) [Levo-T (scored){23}] [Levothroid] [Levoxyl{12}{32}{33}] [Synthroid (scored){13}{22}][Generic]


112 mcg (0.112 mg) (Rx) [Levothroid{24}] [Levoxyl{12}{32}{33}] [Synthroid (scored){13}{22}]


125 mcg (0.125 mg) (Rx) [Levo-T (scored){23}] [Levothroid] [Levoxyl{12}{32}{33}] [Synthroid (scored){13}{22}][Generic]{25}


137 mcg (0.137 mg) (Rx) [Levothroid] [Levoxyl{24}{32}{33}]


150 mcg (0.15 mg) (Rx) [Levo-T (scored){23}] [Levothroid] [Levoxyl{12}{32}{33}] [Synthroid (scored){13}{22}][Generic]


175 mcg (0.175 mg) (Rx) [Levothroid] [Levoxyl{12}{32}{33}] [Synthroid ( scored){13}{22}]


200 mcg (0.2 mg) (Rx) [Levo-T (scored){23}] [Levothroid] [Levoxyl{12}{32}{33}] [Synthroid (scored){13}{22}][Generic]


300 mcg (0.3 mg) (Rx) [Levo-T (scored){23}] [Levothroid] [Levoxyl{12}{32}{33}] [Synthroid (scored){13}{22}][Generic]

Canada—


25 mcg (0.025 mg) (Rx) [PMS-Levothyroxine Sodium (scored){27}] [Synthroid (scored){26}]


50 mcg (0.05 mg) (Rx) [Eltroxin] [PMS-Levothyroxine Sodium (scored){27}] [Synthroid ( scored){26}]


75 mcg (0.075 mg) (Rx) [PMS-Levothyroxine Sodium (scored){27}] [Synthroid (scored){26}]


88 mcg (0.088 mg) (Rx) [Synthroid (scored){26}]


100 mcg (0.1 mg) (Rx) [Eltroxin] [PMS-Levothyroxine Sodium (scored){27}] [Synthroid ( scored){26}]


112 mcg (0.112 mg) (Rx) [Synthroid (scored){26}]


125 mcg (0.125 mg) (Rx) [PMS-Levothyroxine Sodium (scored){27}] [Synthroid (scored){26}]


150 mcg (0.15 mg) (Rx) [Eltroxin] [PMS-Levothyroxine Sodium (scored){27}] [Synthroid ( scored){26}]


175 mcg (0.175 mg) (Rx) [Synthroid (scored){26}]


200 mcg (0.2 mg) (Rx) [Eltroxin] [PMS-Levothyroxine Sodium (scored){27}] [Synthroid ( scored){26}]


300 mcg (0.3 mg) (Rx) [Eltroxin] [PMS-Levothyroxine Sodium (scored){27}] [Synthroid ( scored){26}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.

Auxiliary labeling:
   • Take on empty stomach.
   • Do not take other medicines without your doctor"s advice.

Note: Caution is recommended when changing products because of the potential difference in actual levothyroxine content between brands.




Parenteral Dosage Forms

LEVOTHYROXINE SODIUM INJECTION

Usual adult dose
Hypothyroidism
Intravenous or intramuscular, 50 to 100 mcg (0.05 to 0.1 mg) as a single daily dose.

Myxedema coma or stupor
Initial: Intravenous, 200 to 500 mcg (0.2 to 0.5 mg), even in the elderly; an additional 100 to 300 mcg (0.1 to 0.3 mg) may be given on the second day if improvement has not occurred, followed by continuous daily administration of smaller doses, until the patient can tolerate oral administration.

Note: Smaller doses may be required in patients with concomitant cardiovascular disease.



Usual pediatric dose
Hypothyroidism
Intravenous or intramuscular, daily dose equal to 75% of the usual oral pediatric dose.


Usual geriatric dose
See Usual adult dose.

Strength(s) usually available
U.S.—
Not commercially available.

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer.


LEVOTHYROXINE SODIUM FOR INJECTION

Usual adult dose
See Levothyroxine Sodium Injection.

Usual pediatric dose
See Levothyroxine Sodium Injection.

Usual geriatric dose
See Levothyroxine Sodium Injection.

Size(s) usually available:
U.S.—


200 mcg (0.2 mg) (Rx) [Levothroid] [Synthroid{13}][Generic]{11}


500 mcg (0.5 mg) (Rx) [Levothroid] [Synthroid{13}][Generic]{11}

Canada—


500 mcg (0.5 mg) (Rx) [Synthroid]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Protect from light.

Preparation of dosage form:
Levothyroxine sodium for injection may be reconstituted for parenteral use by adding 0.5, 2, or 5 mL of Sodium Chloride Injection USP (without preservative) to the 50-, 200-, or 500-mcg vial, respectively, and shaking to dissolve, producing a solution containing 100 mcg (0.1 mg) per mL {11} {13}.

Stability:
Solution should be freshly reconstituted immediately prior to each dose. Any unused portion should be discarded.


LIOTHYRONINE

Summary of Differences


Indications:
Advantage over thyroid and thyroglobulin is a predictable effect because of standard hormonal content. May be preferred over levothyroxine when a rapid effect or rapidly reversible effect is desired, or when gastrointestinal absorption processes or peripheral conversion of T 4 (thyroxine) to T 3 (triiodothyronine) is impaired; however, regulation of dosage is more difficult and rapid onset of action may also produce adverse cardiac effects as a result of abrupt changes in metabolic demands.



Pharmacology/pharmacokinetics:
Maximal effects with continued use occur within 48 to 72 hours and persist for up to 72 hours after withdrawal.



Side/adverse effects:
May occur more rapidly with liothyronine than with levothyroxine or thyroid.



General dosing information:
Rapid action and abrupt increase in metabolic demands may produce adverse cardiac effects.

If symptoms of hyperthyroidism occur, withdrawal for 2 to 3 days is recommended before resumption at a lower dose.



Additional Dosing Information
See also General Dosing Information.

When a patient is transferred to liothyronine from other thyroid therapy, the other therapy is discontinued and liothyronine is initiated at a low dosage, increased gradually on the basis of patient response. Keep in mind that the effects of liothyronine occur rapidly, while the effects of other thyroid hormones may persist for several weeks.

Liothyronine may be given in divided daily doses to minimize fluctuations in T 3 concentrations.


Oral Dosage Forms

LIOTHYRONINE SODIUM TABLETS USP

Usual adult dose
Mild hypothyroidism
Initial: Oral, 25 mcg (0.025 mg) a day, with increments of 12.5 or 25 mcg (0.0125 or 0.025 mg) every one or two weeks until the desired result is obtained.

Maintenance: Oral, 25 to 50 mcg (0.025 to 0.05 mg) a day.

Myxedema
Initial: Oral, 2.5 to 5 mcg (0.0025 to 0.005 mg) a day, with increments of 5 to 10 mcg (0.005 to 0.01 mg) every one or two weeks. When 25 mcg (0.025 mg) a day is reached, increments may sometimes be by 12.5 to 25 mcg (0.0125 to 0.025 mg) every one or two weeks.

Maintenance: Oral, 25 to 50 mcg (0.025 to 0.05 mg) a day.

Simple (nontoxic) goiter
Initial: Oral, 5 mcg (0.005 mg) a day, with increments of 5 to 10 mcg (0.005 to 0.01 mg) every one or two weeks. When 25 mcg (0.025 mg) a day is reached, increments may be by 12.5 or 25 mcg (0.0125 or 0.025 mg) every week.

Maintenance: Oral, 50 to 100 mcg (0.05 to 0.1 mg) a day.


Note: In patients with cardiovascular disease, the initial dose is 5 mcg (0.005 mg) a day, with increments of no more than 5 mcg every two weeks. In the elderly also, the initial dose is 5 mcg a day, with increments of no more than 5 mcg at the recommended intervals.


Usual pediatric dose
Cretinism
USP Advisory Panels do not recommend use for cretinism in children because of significant question about T 3 crossing the blood-brain barrier.


Usual geriatric dose
See Usual adult dose.

Strength(s) usually available
U.S.—


5 mcg (0.005 mg) (Rx) [Cytomel]


25 mcg (0.025 mg) (Rx) [Cytomel (scored){28}][Generic]


50 mcg (0.05 mg) (Rx) [Cytomel (scored){28}]

Canada—


5 mcg (0.005 mg) (base) {30} (Rx) [Cytomel]


25 mcg (0.025 mg) (base) (Rx) [Cytomel (scored){30}]

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • Do not take other medicines without your doctor"s advice.



Parenteral Dosage Forms

LIOTHYRONINE SODIUM INJECTION

Usual adult dose
Myxedema coma/precoma
Initial: Intravenous, 25 to 50 mcg every four to twelve hours.{35} Subsequent doses should be determined on the basis of continuous monitoring of the patient's clinical condition and response to the previous injection.{35}

In patients with confirmed or suspected cardiovascular disease, an initial dose of 10 to 20 mcg is suggested{35}.

Note: Oral therapy should be resumed as soon as clinically possible. When switching a patient to liothyronine sodium tablets, liothyronine sodium injection should be discontinued, and oral therapy should be initiated at a low dosage and increased gradually based on the patient's response. When switching a patient to levothyroxine sodium tablets, liothyronine sodium injection should be gradually discontinued because there is a delay in the onset of action of levothyroxine.{35}



Usual adult prescribing limits
Clinical experience with total daily doses greater than 100 mcg per day is limited.{35}

Usual pediatric dose
Safety and efficacy have not been established{35}.

Strength(s) usually available
U.S.—


10 mcg per mL (Rx) [Triostat® (alcohol 6.8% by volume ) (anhydrous citric acid 0.175 mg) (ammonia 2.19 mg [as ammonium hydroxide]){35}]

Canada—
Not commercially available.

Packaging and storage:
Store between 2 and 8 °C (35 and 46 °F),{35} unless otherwise specified by manufacturer.


LIOTRIX

Summary of Differences
Indications: Advantage over thyroid and thyroglobulin is a predictable effect because of standard hormonal content; provision of a product containing T 3 (triiodothyronine) no longer considered an advantage because of natural conversion of T 4 (thyroxine) to T 3 in the tissues.


Oral Dosage Forms

LIOTRIX TABLETS USP

Usual adult and adolescent dose
Hypothyroidism without myxedema
Initial: Oral, 50 mcg (0.05 mg) of levothyroxine and 12.5 mcg (0.0125 mg) of liothyronine a day, with increments of a like amount at monthly intervals until the desired result is obtained.

Maintenance: Oral, 50 to 100 mcg (0.05 to 0.1 mg) of levothyroxine and 12.5 to 25 mcg (0.0125 to 0.025 mg) of liothyronine a day.

Myxedema or hypothyroidism with cardiovascular disease
Initial: Oral, 12.5 mcg (0.0125 mg) of levothyroxine and 3.1 mcg (0.0031 mg) of liothyronine a day, with increments of a like amount at two- to three-week intervals until the desired result is obtained.

Maintenance: Oral, 50 to 100 mcg (0.05 to 0.1 mg) of levothyroxine and 12.5 to 25 mcg (0.0125 to 0.025 mg) of liothyronine a day.


Note: In the elderly, the initial dose is one-fourth to one-half the usual adult dose, doubled at six- to eight-week intervals until the desired result is obtained.


Usual pediatric dose
Cretinism or severe hypothyroidism
See Usual adult and adolescent dose for myxedema.

Hypothyroidism
See Usual adult and adolescent dose for hypothyroidism without myxedema.


Note: Increments in dosage are made at two-week intervals in children.
Dosage should always be based on results of thyroid function tests.


Usual geriatric dose
See Usual adult and adolescent dose.

Strength(s) usually available
U.S.—


Levothyroxine sodium
(mcg)
Liothyronine
sodium (mcg)
Brand name
12.5
3.1
Thyrolar (Rx)
25
6.25
Thyrolar (Rx)
50
12.5
Thyrolar (Rx)
100
25
Thyrolar (Rx)
150
37.5
Thyrolar (Rx)


Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • Do not take other medicines without your doctor"s advice.

Note: Be very careful always to dispense the same brand of liotrix that a patient has received previously.



THYROGLOBULIN

Summary of Differences
Indications: Disadvantages include variable hormonal content of commercial preparations and fluctuation of T 3 (triiodothyronine) and T 4 (thyroxine) concentrations produced.


Oral Dosage Forms

THYROGLOBULIN TABLETS USP

Usual adult and adolescent dose
Hypothyroidism without myxedema
Initial: Oral, 32 mg a day, with increments every one or two weeks until the desired result is obtained.

Maintenance: Oral, 65 to 160 mg a day.

Myxedema or hypothyroidism with cardiovascular disease
Initial: Oral, 16 to 32 mg a day, with increments of a like amount every two weeks until the desired result is obtained.

Maintenance: 65 to 160 mg a day.


Usual pediatric dose
Cretinism or severe hypothyroidism
See Usual adult and adolescent dose for myxedema.

Hypothyroidism
See Usual adult and adolescent dose for hypothyroidism without myxedema.


Note: Dosage should always be based on results of thyroid function tests.
Levothyroxine is considered the drug of choice in the treatment of congenital hypothyroidism.


Strength(s) usually available
U.S.—
Not commercially available.

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • Do not take other medicines without your doctor"s advice.


THYROID

Summary of Differences
Indications: Disadvantages include variable hormonal content of commercial preparations and fluctuation of T 3 (triiodothyronine) and T 4 (thyroxine) concentrations produced.


Oral Dosage Forms

THYROID TABLETS USP

Usual adult and adolescent dose
Hypothyroidism without myxedema
Initial: Oral, 60 mg a day, with increments of 30 {08} mg at monthly intervals until the desired result is obtained.

Maintenance: Oral, 60 to 120 mg a day.

Myxedema or hypothyroidism with cardiovascular disease
Initial: Oral, 15 mg a day, increased to 30 mg a day after two weeks, and to 60 mg a day after a further two weeks. Careful clinical assessment is recommended after one month and two months of treatment at 60 mg a day. If necessary, dosage may then be increased to 120 mg a day. If necessary, further increases of 30 or 60 mg may be made.

Maintenance: Oral, 60 to 120 mg a day.


Note: An initial dose of 7.5 to 15 mg a day is recommended in the elderly; this dose may be doubled every six to eight weeks until the desired result is obtained.


Usual pediatric dose
Cretinism or severe hypothyroidism
See Usual adult and adolescent dose for myxedema.

Hypothyroidism
See Usual adult and adolescent dose for hypothyroidism without myxedema.


Note: Dosage should always be based on results of thyroid function tests.
Levothyroxine is considered the drug of choice in the treatment of congenital hypothyroidism.


Usual geriatric dose
See Usual adult and adolescent dose .

Strength(s) usually available
U.S.—



Regular


15 mg (Rx) [Armour Thyroid{14}{15}{16}][Generic]


30 mg (Rx) [Armour Thyroid{14}{15}{16}] [Westhroid{31}][Generic]


60 mg (Rx) [Armour Thyroid{14}{15}{16}] [Westhroid{31}][Generic]


90 mg (Rx) [Armour Thyroid{14}{15}{16}]


120 mg (Rx) [Armour Thyroid{14}{15}{16}] [Westhroid{31}][Generic]


180 mg (Rx) [Armour Thyroid{14}{15}{16}] [Westhroid{31}][Generic]


240 mg (Rx) [Armour Thyroid{14}{15}{16}] [Westhroid{31}]


300 mg (Rx) [Armour Thyroid{14}{15}{16}] [Westhroid{31}][Generic]



Bovine


30 mg (Rx) [Thyrar{14}{17}{18}]


60 mg (Rx) [Thyrar{14}{17}{18}]


120 mg (Rx) [Thyrar{14}{17}{18}]



Strong (contains iodine 0.3%)


30 mg (Rx) [Thyroid Strong{14}{19}]


60 mg (Rx) [Thyroid Strong{14}{19}]


120 mg (Rx) [Thyroid Strong{14}{19}]


180 mg (Rx) [Thyroid Strong{14}{19}]

Canada—



Regular


30 mg (Rx)[Generic]


60 mg (Rx)[Generic]


125 mg (Rx)[Generic]

Note: Administration of strengths above 120 mg may result in thyrotoxic symptoms {08}.


Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight container.

Auxiliary labeling:
   • Do not take other medicines without your doctor"s advice.



Revised: 06/21/2000



References
  1. Cytomel package insert (SKF—US), 1988.
  1. Cytomel (SKF). In: CPS Compendium of pharmaceuticals and specialties. 23rd ed. Ottawa: Canadian Pharmaceutical Association, 1988.
  1. Reviewer comment, 1987.
  1. JAMA 1985 Oct 18; 254: 2109-10.
  1. Neurology 1985 Dec; 35: 1792-3.
  1. Clin Pharm 1986 Apr; 5: 304-18.
  1. Clin Pharm 1986 May; 5: 385-95.
  1. Panel comments, 1989.
  1. Reviewer comments, 1989.
  1. Synthroid (Flint). In: PDR 1988.
  1. Levothyroxine sodium for injection package insert (Lyphomed—US), Rev 5/91, Rec 12/31/91.
  1. Levoxine tablets package insert (Daniels—US), Rev 4/91, Rec 7/19/91.
  1. Synthroid tablets and injection package insert (Boots—US), Rev 4/30/90, Rec 1/17/91.
  1. Olin BR, editor. Drug facts and comparisons. St. Louis: Facts and Comparisons Inc., 1991 Jun: 132h.
  1. Thyroid (Armour Thyroid, Forest). In: PDR Physicians" desk reference. 48th ed. 1994. Montvale, NJ: Medical Economics Data, 1994: 952.
  1. Red book 1993. Montvale, NJ: Medical Economics Data, 1993. March 1994 Update: 6.
  1. Thyroid (Thyrar, Rhône-Poulenc Rorer). In: PDR Physicians" desk reference. 48th ed. 1994. Montvale, NJ: Medical Economics Data, 1994: 1845.
  1. Red book 1993. Montvale, NJ: Medical Economics Data, 1993. March 1994 Update: 43.
  1. Red book 1993. Montvale, NJ: Medical Economics Data, 1993: 555.
  1. Thyroid (S-P-T, Fleming). In: PDR Physicians" desk reference. 48th ed. 1994. Montvale, NJ: Medical Economics Data, 1994: 948.
  1. Red book 1993. Montvale, NJ: Medical Economics Data, 1993: 493.
  1. Olin BR, editor. Drug facts and comparisons. St. Louis: Facts and Comparisons Inc., 1991 Jun: 133.
  1. Levothroxine sodium package insert (Levo-T, Lederle—US), Rev 7/92, Rec 12/93.
  1. Levothyroxine sodium (Levothroid, Forest). In: PDR Physicians" desk reference. 48th ed. 1994. Montvale, NJ: Medical Economics Data, 1994: 955.
  1. Red book 1993. Montvale, NJ: Medical Economics Data, 1993. March 1994 Update: 25.
  1. Levothyroxine sodium (Synthroid, Boots). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 29th ed. Ottawa: Canadian Pharmaceutical Association, 1994: 1270.
  1. Levothyroxine sodium (PMS-Levothyroxine, Pharmascience). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 29th ed. Ottawa: Canadian Pharmaceutical Association, 1994: 1035.
  1. Olin BR, editor. Drug facts and comparisons. St. Louis: Facts and Comparisons Inc., 1992 Apr: 133b.
  1. Liothyronine sodium (Triostat, SmithKline Beecham). In: PDR Physicians" desk reference. 48th ed. 1994. Montvale, NJ: Medical Economics Data, 1994: 2295.
  1. Liothyronine sodium (Cytomel, SmithKline Beecham). In: Krogh CME, editor. CPS Compendium of pharmaceuticals and specialties. 29th ed. Ottawa: Canadian Pharmaceutical Association, 1994: 317.
  1. Red book 1993. Montvale, NJ: Medical Economics Data, 1993: 602.
  1. Levothyroxine package insert (Levoxyl, Daniels—US), Rev 8/94, Rec 10/94.
  1. Manufacturer"s letter, 10/94.
  1. Manufacturer"s letter, 11/94.
  1. Product Information: Triostat®, liothyronine sodium injection (T3). Jones Pharma Inc, St. Louis, MO (PI revised 4/1998) reviewed 6/2000.
Hide
(web4)