Eltroxin (Levothyroxine Sodium)


Glaxo Wellcome

Levothyroxine Sodium

Hypothyroidism Therapy

Action And Clinical Pharmacology: Levothyroxine sodium is the monosodium salt of the levorotatory isomer of thyroxine (tetraiodothyronine), the principal hormone secreted by the normal thyroid gland.

Pharmacokinetics: Following oral administration, the absorption of levothyroxine is incomplete and variable (50 to 75%), especially when taken with food. Once absorbed, synthetic levothyroxine is indistinguishable from the endogenous hormone.

Levothyroxine is nearly totally bound to serum proteins and has an elimination half-life of 6 to 7 days in the euthyroid subject. Half-life is shortened in hyperthyroidism and prolonged in hypothyroidism and in pregnancy. Deiodination of levothyroxine (T4) to 1-triiodothyronine (T3) occurs in various tissues, particularly liver and kidney. T3 is approximately 4 times as potent as T4 on a weight basis.

The mechanism of action of thyroid hormones is not completely understood. The principle effect is to increase the metabolic rate of body tissues. Thyroid hormones have both catabolic and anabolic effects, and are therefore involved in normal metabolism, growth, and development, especially the development of the CNS in infancy.

Indications And Clinical Uses: Specific hormonal replacement therapy in the presence of hypothyroidism of any etiology.

Contra-Indications: Patients with hypersensitivity to any ingredient of the tablets and patients with thyrotoxicosis, acute myocardial infarction or uncorrected adrenal insufficiency.

Manufacturers’ Warnings In Clinical States: Lactation: In euthyroid lactating mothers, levothyroxine (endogenous or exogenous) may be secreted into breast milk in amounts sufficient to mask signs of hypothyroidism in the nursing infant.

The use of levothyroxine in the treatment of obesity in patients who are not hypothyroid has been shown to be ineffective and potentially harmful.

Precautions: Pregnancy: Levothyroxine does not readily cross the placenta, and when successfully employed to render or maintain the patient in an euthyroid state, therapy is considered to be warranted in pregnant patients. Hypo- or hyperthyroid activity in the mother may unfavorably influence the fetal outcome or well being.

Due to the profound effects of thyroid hormones on energy-requiring metabolic processes, the administration of levothyroxine to a hypothyroid patient may unmask occult cardiovascular, endocrine or metabolic disease.

Long standing hypothyroidism is associated with atherogenesis, which may or may not manifest itself in the hypometabolic state. In such cases levothyroxine should be administered with extreme caution employing low initial dosage increased slowly by small increments, as even a gradual restoration of normal metabolic rate may result in development or exacerbation of myocardial ischemia and angina. In some patients, cardiovascular status may be so compromised that the metabolic demands of the euthyroid state cannot be met, despite the employment of appropriate antianginal therapy. Clinical judgment may then dictate a less-than-complete restoration of thyroid status.

Endocrine disorders such as diabetes mellitus, diabetes insipidus, Addison’s disease (adrenal insufficiency) and hypopituitarism are characterized by signs and symptoms which may be diminished in severity or obscured by hypothyroidism.

Treatment with levothyroxine may require that appropriate adjustments in therapy for these concomitant disorders be made. In particular, when hypothyroidism is accompanied by adrenal insufficiency (such as in panhypopituitarism), appropriate adrenocortical replacement therapy should be instituted prior to commencement of treatment with levothyroxine in order to prevent the possible precipitation of Addisonian crisis.

Slightly excessive dosage of thyroid agents were previously recommended for replacement therapy in congenital hypothyroidism (cretinism), since it was thought that slight underdosage was harmful while slightly excessive dosage was not. However, it is currently recommended that excessive dosage be avoided since minimal brain damage has occurred in children with thyrotoxicosis during infancy and excessive dosage may accelerate bone age and cause premature craniosynostosis (see Dosage).

The intestinal absorption of levothyroxine may be impaired in patients with certain malabsorption states, particularly celiac sprue (gluten enteropathy). Higher dosages of levothyroxine may be required in such patients, especially during exacerbations of the enteropathy.

Levothyroxine should be used with caution in elderly patients who may be more sensitive to the effects of thyroid hormones (see Dosage).

Due to potential differences in potency and bioavailability, different levothyroxine products may not be interchangeable. Patients stabilized on a particular brand of levothyroxine should not be unnecessarily switched to another brand. When such a brand change is necessary, the patients must be carefully re-evaluated to assess the potential need for dosage adjustment.

Drug Interactions: Thyroid hormones potentiate the hypoprothrombinemic effects of oral anticoagulant agents such as warfarin. When treatment with levothyroxine is initiated in patients receiving oral anticoagulants, the prothrombin time should be determined frequently and the anticoagulant dosage reduced appropriately.

Administration of levothyroxine to a diabetic patient may result in an increase in the patient’s requirements for insulin and/or hypoglycemic medication since thyroxine raises blood sugar levels (see above).

Cholestyramine resin binds levothyroxine in the intestinal tract and substantially impairs its absorption. When the 2 agents must be used concurrently the levothyroxine dose should be taken at least 1 hour before or 4 hours after the dose of cholestyramine, with regular monitoring of thyroid function.

Anticonvulsants such as carbamazepine and phenytoin enhance the metabolism of thyroid hormones and may displace them from plasma proteins.

Phenobarbital induces hepatic enzymes and increases the rate of degradation of thyroid hormones. The dosage of levothyroxine may need to be increased when concurrent therapy with phenobarbital is employed.

Beta-adrenergic blocking agents may decrease peripheral conversion of T4 to T3, thereby reducing the efficacy of exogenous levothyroxine.

Estrogens increase serum thyroxine-binding globulin levels, thereby decreasing the unbound fractions of T3 and T4. Administration of estrogen-containing preparations (such as oral contraceptives) to hypothyroid patients may cause an increase in their levothyroxine requirements.

Patients receiving thyroid replacement therapy who undergo anesthesia with ketamine should be closely monitored for possible hypertension and tachycardia.

Concurrent use of sympathomimetic agents or tricyclic antidepressants with thyroid hormones may result in enhanced effects of either medication. In patients with coronary artery disease receiving thyroid replacement therapy, administration of sympathomimetic agents increases the risk of coronary insufficiency.

If coadministered with cardiac glycosides, adjustment of dosage of cardiac glycoside may be necessary.

Sucralfate or aluminium-containing antacids may decrease the absorption of levothyroxine. Adjustment of the levothyroxine dose, or cessation of the aluminum-containing medication may be necessary.

Simultaneous ingestion of ferrous sulfate and levothyroxine causes a reduction in thyroxine efficacy. When the two agents must be used concurrently, the levothyroxine and ferrous sulfate doses must be separated by an interval of 2 hours or more, with regular monitoring of thyroid function.

Laboratory Test Interactions : Various physiologic and pathologic conditions or certain drugs can interfere with thyroid function tests and their interpretation. Serum thyroxine-binding globulin (TBG) is increased in pregnancy, on estrogen therapy, or in patients using estrogen-containing oral contraceptives. Infectious hepatitis may also increase serum TBG concentration. Decreased TBG is found in patients on androgen or corticosteroid therapy and also in cases of nephrosis and acromegaly. Some drugs such as phenylbutazone and salicylates bind competitively to TBG or thyroxine-binding prealbumin. Familial hyper-or hypo-thyroxine-binding globulinemias have been reported.

Adverse Reactions: Adverse reactions to levothyroxine are confined to hypersensitivity to or intolerance of an ingredient of the tablets, and toxicity due to overdosage of levothyroxine (see Overdose: Symptoms and Treatment).

Symptoms And Treatment Of Overdose: Symptoms and Treatment: Overdosage with levothyroxine can be expected to produce the typical signs and symptoms of thyrotoxicosis. These may include weight loss, increased appetite, palpitations, nervousness, diarrhea, abdominal cramps, sweating, tachycardia, increased pulse and blood pressures, angina pectoris, cardiac dysrhythmias, tremors, headache, insomnia, heat intolerance, fever and dysmenorrhea.

Severe overdosage is equivalent to thyroid storm and may be manifested by coma, cardiac decompensation, and possibly death secondary to cardiac dysrhythmia or failure. The effects of acute overdosage of levothyroxine may take several days to appear.

The manifestations of levothyroxine overdosage should be managed by discontinuation of levothyroxine for 2 to 7 days followed by resumption of treatment with lower doses.

The management of acute severe overdosage should consist principally of reducing absorption of the drug and counteracting central and peripheral effects, mainly those of increased sympathetic nervous activity. Initially, the stomach should be emptied immediately by inducing emesis or by gastric lavage. If the patient is comatose, having seizures, or lacks the gag reflex, gastric lavage may be performed if an endotracheal tube with cuff inflated is in place to prevent aspiration of vomitus. Oxygen may be administered and ventilation maintained. If congestive heart failure develops, cardiac glycosides may be administered. Measures to control fever, hypoglycemia, or fluid loss should be initiated as necessary. A b-adrenergic blocking agent may be useful to counteract many of the effects of increased sympathetic activity. Provided no contraindications for its use exist, propranolol may be administered i.v. in a dosage of 1 to 3 mg every 10 minutes, or orally in a dosage of 80 to 100 mg/day. However, propylthiouracil and other antithyroid agents are not effective in the treatment of thyrotoxicosis due to overdosage of exogenous levothyroxine.

Dosage And Administration: Dosage of levothyroxine must be carefully adjusted according to individual requirements and response. The age and general physical condition of the patients and the severity and duration of hypothyroid symptoms determine the initial dosage and rate at which dosage may be increased to the eventual maintenance dosage (see Precautions). Adjustment of levothyroxine dosage should be based mainly on the patient’s clinical response and confirmed by appropriate laboratory tests. Laboratory tests alone should not be relied upon to guide therapy.

For purposes of conversion, levothyroxine sodium (T4) 100 µg is usually considered equivalent to desiccated thyroid 60 mg, thyroglobulin 60 mg, or liothyronine sodium (T3) 25 µg. However, these are rough guidelines only and do not obviate the careful re-evaluation of a patient when switching thyroid hormone preparations, including a change from one brand of levothyroxine to another (see Precautions).

Information for the Patient: Patients on thyroid preparations and parents of children on thyroid therapy should be informed that 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.

Patients should immediately report to the physician experiences during the course of therapy of 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.

Patients with concurrent diabetes mellitus or who are on concurrent oral anticoagulant therapy should be warned of the need for close monitoring and possible dosage adjustments.

Parents should be warned that 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 normally the rule.

Adults: For the management of mild hypothyroidism, the usual initial dose is 50 µg once daily. Dosage may be increased in increments of 25 to 50 µg/day at intervals of 2 to 4 weeks until the desired response is obtained.

For the management of severe hypothyroidism the usual initial dosage is 12.5 to 25 µg once daily. Dosage may be increased by increments of 25 to 50 µg/day at intervals of 2 to 4 weeks until the desired response is obtained. The usual maintenance dosage for full replacement therapy is 100 to 200 µg/day, although certain patients may require higher dosages. Failure to respond adequately to dosages exceeding 300 to 400 µg/day is rare and should prompt re-evaluation of the diagnosis, or suggest the presence of malabsorption or patient noncompliance.

For geriatric patients with hypothyroidism, the usual initial dosage is 12.5 to 50 µg once daily. Dosage may be increased at intervals of 3 to 8 weeks until the desired response is obtained. Thyroid hormone replacement requirements are about 25% lower in patients over the age of 60 years than in younger adults.

Infants and Children: In infants and children, it is essential to achieve rapid and complete thyroid replacement because of the critical importance of thyroid hormones in sustaining growth and maturation, including the normal development of the CNS. In general, the dosage requirements of children, on a per body weight basis, are higher than those of adults.

Premature neonates weighing less than 2 kg and neonates at risk of cardiac failure may receive an initial dosage of 25 µg once daily; dosage may be increased to 50 µg once daily in 4 to 6 weeks.

Availability And Storage: 50 µg: Each white tablet contains: levothyroxine sodium USP 50 µg. Nonmedicinal ingredients: acacia powder, corstarch, lactose and magnesium stearate. Gluten- and tartrazine-free. Bottles of 100 and 500.

100 µg: Each yellow tablet contains: levothyroxine sodium 100 µg. Nonmedicinal ingredients: acacia powder, Colorcon yellow, cornstarch, lactose and magnesium stearate. Gluten- and tartrazine-free. Bottles of 500.

150 µg: Each blue tablet contains: levothyroxine sodium 150 µg. Nonmedicinal ingredients: acacia powder, Colorcon blue, cornstarch, lactose and magnesium stearate. Gluten- and tartrazine-free. Bottles of 500.

200 µg: Each pink tablet contains: levothyroxine sodium 200 µg. Nonmedicinal ingredients: acacia powder, cornstarch, erythrosine, lactose and magnesium stearate. Gluten- and tartrazine-free. Bottles of 500.

300 µg: Each green tablet contains: levothyroxine sodium 300 µg. Nonmedicinal ingredients: acacia powder, Colorcon green, cornstarch, lactose and magnesium stearate. Gluten- and tartrazine-free. Bottles of 100 and 500.

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ELTROXIN® Glaxo Wellcome Levothyroxine Sodium Hypothyroidism Therapy

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