LEVOTHYROXINE SODIUM — levothyroxine sodium anhydrous injection, powder, lyophilized, for solution
Par Pharmaceutical Inc.
WARNING: NOT FOR TREATMENT OF OBESITY OR FOR WEIGHT LOSS
Thyroid hormones, including Levothyroxine Sodium for Injection, should not be used for the treatment of obesity or for weight loss. ( 5.3 )
Larger doses may produce serious or even life threatening manifestations of toxicity. ( 6 )
1 INDICATIONS AND USAGE
Levothyroxine Sodium for Injection is indicated for the treatment of myxedema coma. Important Limitations of Use: The relative bioavailability between Levothyroxine Sodium for Injection and oral levothyroxine products has not been established. Caution should be used when switching patients from oral levothyroxine products to Levothyroxine Sodium for Injection as accurate dosing conversion has not been studied.
2 DOSAGE AND ADMINISTRATION
An initial intravenous loading dose of Levothyroxine Sodium for Injection between 300 to 500 mcg, followed by once daily intravenous maintenance doses between 50 and 100 mcg, should be administered, as clinically indicated, until the patient can tolerate oral therapy. The age, general physical condition, cardiac risk factors, and clinical severity of myxedema and duration of myxedema symptoms should be considered when determining the starting and maintenance dosages of Levothyroxine Sodium for Injection.
Levothyroxine Sodium for Injection produces a gradual increase in the circulating concentrations of the hormone with an approximate half-life of 9 to 10 days in hypothyroid patients. Daily administration of Levothyroxine Sodium for Injection should be maintained until the patient is capable of tolerating an oral dose and is clinically stable. For chronic treatment of hypothyroidism, an oral dosage form of levothyroxine should be used to maintain a euthyroid state. Relative bioavailability between Levothyroxine Sodium for Injection and oral levothyroxine products has not been established. Based on medical practice, the relative bioavailability between oral and intravenous administration of Levothyroxine Sodium for Injection is estimated to be from 48 to 74%. Due to differences in absorption characteristics of patients and the oral levothyroxine product formulations, TSH and thyroid hormone levels should be measured a few weeks after initiating oral levothyroxine and dose adjusted accordingly.
2.2 Dosing in the Elderly and in Patients with Cardiovascular Disease
Intravenous levothyroxine may be associated with cardiac toxicity–including arrhythmias, tachycardia, myocardial ischemia and infarction, or worsening of congestive heart failure and death–in the elderly and in those with underlying cardiovascular disease. Therefore, cautious use, including doses in the lower end of the recommended range, may be warranted in these populations.
2.3 Reconstitution Directions
Reconstitute the lyophilized Levothyroxine Sodium for Injection by aseptically adding 5 mL of 0.9% Sodium Chloride Injection, USP only. Shake vial to ensure complete mixing. The resultant solution will have a final concentration of approximately 20 mcg per mL, 40 mcg per mL and 100 mcg per mL for the 100 mcg, 200 mcg and 500 mcg vials, respectively. Reconstituted drug product is preservative free and is stable for 4 hours. Discard any unused portion. DO NOT ADD LEVOTHYROXINE SODIUM FOR INJECTION TO OTHER IV FLUIDS. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.
3 DOSAGE FORMS AND STRENGTHS
Levothyroxine Sodium for Injection is supplied as a lyophilized powder at three strengths in single dose amber-colored vials: 100 mcg, 200 mcg and 500 mcg.
5 WARNINGS AND PRECAUTIONS
5.1 Risk of Cardiac Complications in Elderly and in Patients with Cardiovascular Disease
Excessive bolus dosing of Levothyroxine Sodium for Injection (greater than 500 mcg) are associated with cardiac complications, particularly in the elderly and in patients with an underlying cardiac condition. Adverse events that can potentially be related to the administration of large doses of Levothyroxine Sodium for Injection include arrhythmias, tachycardia, myocardial ischemia and infarction, or worsening of congestive heart failure and death. Cautious use, including doses in the lower end of the recommended range, may be warranted in these populations. Close observation of the patient following the administration of Levothyroxine Sodium for Injection is advised.
5.2 Need for Concomitant Glucocorticoids and Monitoring for Other Diseases in Patients with Endocrine Disorders
Occasionally, chronic autoimmune thyroiditis, which can lead to myxedema coma, may occur in association with other autoimmune disorders such as adrenal insufficiency, pernicious anemia, and insulin‑dependent diabetes mellitus. Patients should be treated with replacement glucocorticoids prior to initiation of treatment with Levothyroxine Sodium for Injection, until adrenal function has been adequately assessed. Failure to do so may precipitate an acute adrenal crisis when thyroid hormone therapy is initiated, due to increased metabolic clearance of glucocorticoids by thyroid hormone. With initiation of Levothyroxine Sodium for Injection, patients with myxedema coma should also be monitored for previously undiagnosed diabetes insipidus.
5.3 Not Indicated for Treatment of Obesity
Thyroid hormones, including Levothyroxine Sodium for Injection, either alone or with other therapeutic agents, should not be used for the treatment of obesity or for weight loss. In euthyroid patients, doses within the range of daily hormonal requirements are ineffective for weight reduction. Larger doses may produce serious or even life threatening manifestations of toxicity, particularly when given in association with sympathomimetic amines such as those used for their anorectic effects [see Adverse Reactions ( 6) and Overdosage ( 10)].
6 ADVERSE REACTIONS
ExcessI doses of levothyroxine can predispose to signs and symptoms compatible with hyperthyroidism. The signs and symptoms of thyrotoxicosis include, but are not limited to: exophthalmic goiter, weight loss, increased appetite, palpitations, nervousness, diarrhea, abdominal cramps, sweating, tachycardia, increased pulse and blood pressure, cardiac arrhythmias, angina pectoris, tremors, insomnia, heat intolerance, fever, and menstrual irregularities.
7 DRUG INTERACTIONS
Many drugs affect thyroid hormone pharmacokinetics and metabolism (e.g., synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to Levothyroxine Sodium for Injection. In addition, thyroid hormones and thyroid status have varied effects on the pharmacokinetics and actions of other drugs (see Section 12.3).
7.1 Antidiabetic Therapy
Addition of levothyroxine to antidiabetic or insulin therapy may result in increased antidiabetic agent or insulin requirements. Careful monitoring of diabetic control is recommended, especially when thyroid therapy is started, changed, or discontinued.
7.2 Oral Anticoagulants
Levothyroxine increases the response to oral anticoagulant therapy. Therefore, a decrease in the dose of anticoagulant may be warranted with correction of the hypothyroid state or when the Levothyroxine Sodium for Injection dose is increased. Prothrombin time should be closely monitored to permit appropriate and timely dosage adjustments.
7.3 Digitalis Glycosides
The therapeutic effects of digitalis glycosides may be reduced by levothyroxine. Serum digitalis glycoside levels may be decreased when a hypothyroid patient becomes euthyroid, necessitating an increase in the dose of digitalis glycosides.
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