لووتیروکسین سدیم

تزریق لووتیروکسین سدیم برای درمان میکسدم کما اندیکاسیون دارد. محدودیت های استفاده: فراهمی زیستی نسبی بین تزریقی لووتیروکسین سدیم و محصولات خوراکی لووتیروکسین ثابت نشده است. هنگام تعویض بیماران از محصولات خوراکی لووتیروکسین به تزریق لووتیروکسین سدیم باید احتیاط کرد زیرا تبدیل دوز دقیق مورد مطالعه قرار نگرفته است. لووتیروکسین سدیم یک محصول ال تیروکسین است. تزریق سدیم لووتیروکسین (T4) برای درمان میکسدم کما نشان داده شده است. ( 1 ) محدودیت های مهم استفاده: فراهمی زیستی نسبی این دارو ثابت نشده است. هنگام تبدیل بیماران از لووتیروکسین خوراکی به داخل وریدی احتیاط کنید. (1)

لووتیروکسین سدیم تزریقی 100 میکروگرم بر میلی لیتر یک محلول شفاف، بی رنگ تا کمی زرد است که به صورت 1 میلی لیتر در هر ویال عرضه می شود. تزریق: mcg/ml 100 در ویال تک دوز. راه حل آماده برای استفاده. (3)

هیچ کدام

5 هشدارها و اقدامات احتیاطی عوارض جانبی قلبی در سالمندان و در بیماران مبتلا به بیماری قلبی عروقی زمینه ای: درمان بیش از حد ممکن است باعث آریتمی، تاکی کاردی، ایسکمی میوکارد و انفارکتوس، یا بدتر شدن نارسایی احتقانی قلب و مرگ، به ویژه در بیماران مبتلا به بیماری قلبی عروقی شود. در بیماران مسن و بیماران مبتلا به بیماری قلبی عروقی زمینه ای با دوزهای پایین تر شروع شود و پس از تجویز بیماران را تحت نظر بگیرید (5.1). بحران حاد آدرنال در بیماران مبتلا به نارسایی همزمان آدرنال شروع هورمون درمانی تیروئید قبل از شروع درمان با گلوکوکورتیکوئید ممکن است باعث بروز بحران حاد آدرنال در بیماران مبتلا به نارسایی غدد فوق کلیوی شود. بیماران مبتلا به نارسایی آدرنال را با گلوکوکورتیکوئیدهای جایگزین قبل از شروع درمان درمان کنید (5.2). بدتر شدن کنترل دیابت: ممکن است کنترل قند خون را بدتر کند و منجر به افزایش نیاز به داروی ضد دیابت یا انسولین شود. کنترل قند خون را به دقت کنترل کنید (5.3)

5.1 خطر عوارض قلبی در سالمندان و بیماران مبتلا به بیماری قلبی عروقی دوز بولوس بیش از حد تزریق لووتیروکسین سدیم (بیش از 500 میکروگرم) با عوارض قلبی، به ویژه در سالمندان و در بیماران مبتلا به بیماری قلبی زمینه ای همراه است. عوارض جانبی که به طور بالقوه می تواند مربوط به تجویز دوزهای زیاد لووتیروکسین تزریقی باشد شامل آریتمی، تاکی کاردی، ایسکمی و انفارکتوس میوکارد، یا بدتر شدن نارسایی احتقانی قلب و مرگ است. استفاده محتاطانه، از جمله دوزهای پایین تر از محدوده توصیه شده، ممکن است در این جمعیت ها ضروری باشد. تحت نظر گرفتن دقیق بیمار پس از تزریق لووتیروکسین سدیم توصیه می شود.

5.2 بحران حاد آدرنال در بیماران مبتلا به نارسایی همزمان آدرنال تیروئیدیت خودایمنی مزمن، که می تواند به کما میکسدم منجر شود، ممکن است همراه با سایر اختلالات خودایمنی مانند نارسایی آدرنال، کم خونی خطرناک و دیابت ملیتوس وابسته به انسولین رخ دهد. بیماران باید قبل از شروع درمان با تزریق لووتیروکسین سدیم، با گلوکوکورتیکوئیدهای جایگزین، تا زمانی که عملکرد آدرنال به اندازه کافی ارزیابی شود، تحت درمان قرار گیرند. در صورت عدم انجام این کار ممکن است با شروع هورمون درمانی تیروئید، به دلیل افزایش کلیرانس متابولیک گلوکوکورتیکوئیدها توسط هورمون تیروئید، یک بحران حاد آدرنال ایجاد شود. با شروع تزریق لووتیروکسین سدیم، بیماران مبتلا به کما میکسدما نیز باید از نظر دیابت بی مزه قبلا تشخیص داده نشده تحت نظر باشند.

5.3 بدتر شدن کنترل دیابت افزودن درمان با لووتیروکسین در بیماران مبتلا به دیابت ممکن است کنترل قند خون را بدتر کرده و منجر به افزایش نیاز به داروی ضد دیابت یا انسولین شود. کنترل قند خون را به دقت کنترل کنید [به تداخلات دارویی (7.1) مراجعه کنید].

5.1 خطر عوارض قلبی در سالمندان و بیماران مبتلا به بیماری قلبی عروقی دوز بولوس بیش از حد تزریق لووتیروکسین سدیم (بیش از 500 میکروگرم) با عوارض قلبی، به ویژه در سالمندان و در بیماران مبتلا به بیماری قلبی زمینه ای همراه است. عوارض جانبی که به طور بالقوه می تواند مربوط به تجویز دوزهای زیاد لووتیروکسین تزریقی باشد شامل آریتمی، تاکی کاردی، ایسکمی و انفارکتوس میوکارد، یا بدتر شدن نارسایی احتقانی قلب و مرگ است. استفاده محتاطانه، از جمله دوزهای پایین تر از محدوده توصیه شده، ممکن است در این جمعیت ها ضروری باشد. تحت نظر گرفتن دقیق بیمار پس از تزریق لووتیروکسین سدیم توصیه می شود.

5.2 بحران حاد آدرنال در بیماران مبتلا به نارسایی همزمان آدرنال تیروئیدیت خودایمنی مزمن، که می تواند به کما میکسدم منجر شود، ممکن است همراه با سایر اختلالات خودایمنی مانند نارسایی آدرنال، کم خونی خطرناک و دیابت ملیتوس وابسته به انسولین رخ دهد. بیماران باید قبل از شروع درمان با تزریق لووتیروکسین سدیم، با گلوکوکورتیکوئیدهای جایگزین، تا زمانی که عملکرد آدرنال به اندازه کافی ارزیابی شود، تحت درمان قرار گیرند. در صورت عدم انجام این کار ممکن است با شروع هورمون درمانی تیروئید، به دلیل افزایش کلیرانس متابولیک گلوکوکورتیکوئیدها توسط هورمون تیروئید، یک بحران حاد آدرنال ایجاد شود. با شروع تزریق لووتیروکسین سدیم، بیماران مبتلا به کما میکسدما نیز باید از نظر دیابت بی مزه قبلا تشخیص داده نشده تحت نظر باشند.

5.3 بدتر شدن کنترل دیابت افزودن درمان با لووتیروکسین در بیماران مبتلا به دیابت ممکن است کنترل قند خون را بدتر کرده و منجر به افزایش نیاز به داروی ضد دیابت یا انسولین شود. کنترل قند خون را به دقت کنترل کنید [به تداخلات دارویی (7.1) مراجعه کنید].

Adverse reactions associated with levothyroxine are primarily those of hyperthyroidism due to therapeutic overdosage [see Warnings and Precautions (5) , Overdosage (10) ] . They include the following: General: fatigue, increased appetite, weight loss, heat intolerance, fever, excessive sweating Central nervous system: headache, hyperactivity, nervousness, anxiety, irritability, emotional lability, insomnia Musculoskeletal: tremors, muscle weakness, muscle spasm Cardiovascular: palpitations, tachycardia, arrhythmias, increased pulse and blood pressure, heart failure, angina, myocardial infarction, cardiac arrest Respiratory: dyspnea Gastrointestinal: diarrhea, vomiting, abdominal cramps, elevations in liver function tests Dermatologic: flushing, rash Seizures have been reported rarely with the institution of levothyroxine therapy. Hypersensitivity Reactions Hypersensitivity reactions to inactive ingredients have occurred in patients treated with thyroid hormone products. These include urticaria, pruritus, skin rash, flushing, angioedema, various gastrointestinal symptoms (abdominal pain, nausea, vomiting and diarrhea), fever, arthralgia, serum sickness, and wheezing. Hypersensitivity to levothyroxine itself is not known to occur. Adverse reactions associated with Levothyroxine Sodium Injection are primarily those of hyperthyroidism due to therapeutic overdosage: fatigue, increased appetite, weight loss, heat intolerance, fever, excessive sweating, headache, hyperactivity, nervousness, anxiety, irritability, emotional lability, insomnia, tremors, muscle weakness, muscle spasm, palpitations, tachycardia, arrhythmias, increased pulse and blood pressure, heart failure, angina, myocardial infarction, cardiac arrest, dyspnea, diarrhea, vomiting, abdominal cramps, elevations in liver function tests, flushing, and rash. ( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Hikma at us.hikma@primevigilance.com or call 1-877-845-0689 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

In general, the signs and symptoms of overdosage with levothyroxine are those of hyperthyroidism [see Warnings and Precautions (5) and Adverse Reactions (6)]. In addition, confusion and disorientation may occur. Cerebral embolism, shock, coma, and death have been reported. Excessive doses of Levothyroxine Sodium Injection (greater than 500 mcg) are associated with cardiac complications in patients with underlying cardiac disease. Treatment of Overdosage Levothyroxine Sodium Injection should be reduced in dose or temporarily discontinued if signs or symptoms of overdosage occur. To obtain up-to-date information about the treatment of overdose, a good resource is the certified Regional Poison Control Center. In managing overdosage, consider the possibility of multiple drug overdoses, interaction among drugs, and unusual drug kinetics in the patient. In the event of an overdose, appropriate supportive treatment should be initiated as dictated by the patient’s medical status.

Elderly and those with underlying cardiovascular disease should receive doses at the lower end of the recommended range. ( 8.5 )

8.1 Pregnancy Risk Summary The clinical data in pregnant women treated with oral levothyroxine to treat hypothyroidism do not indicate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are no data available on the use of Levothyroxine Sodium Injection in pregnant women. There are risks to the mother and fetus associated with myxedema coma in pregnancy (see Clinical Considerations) . No developmental or reproductive toxicity studies in animals have been conducted with Levothyroxine Sodium Injection. The estimated background risks of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have background risks of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Myxedema coma is a medical emergency that can be fatal if left untreated. Delaying treatment in pregnant women with myxedema coma increases the risk of maternal and fetal morbidity and mortality. Life-sustaining therapy for pregnant women with myxedema coma should not be withheld due to potential concerns regarding the effects of Levothyroxine Sodium Injection on the fetus.

8.2 Lactation Risk Summary Published studies report that levothyroxine is present in human milk following the administration of oral levothyroxine. No adverse effects on the breastfed infant have been reported, and there is no information on the effects of levothyroxine on milk production from levothyroxine oral treatment. There are no available data with use of Levothyroxine Sodium Injection in lactating women. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Levothyroxine Sodium Injection and any potential adverse effects on the breastfed infant from Levothyroxine Sodium Injection or from the underlying maternal condition.

8.4 Pediatric Use The safety and effectiveness of Levothyroxine Sodium Injection have not been established in pediatric patients.

8.5 Geriatric Use and Patients with Underlying Cardiovascular Disease See Section 2, Dosage and Administration, for full prescribing information in the geriatric patient population. Because of the increased prevalence of cardiovascular disease in the elderly, cautious use of Levothyroxine Sodium Injection in the elderly and in patients with known cardiac risk factors is advised. Atrial fibrillation is a common side effect associated with levothyroxine treatment in the elderly [see Dosage and Administration (2) and Warnings and Precautions (5) ].

8.6 Renal Impairment Serum creatinine and levothyroxine levels should be closely monitored in patients with severe renal impairment receiving intravenous levothyroxine with betadex sulfobutyl (SBECD) [See Clinical Pharmacology (12.3) ].

8.5 Geriatric Use and Patients with Underlying Cardiovascular Disease See Section 2, Dosage and Administration, for full prescribing information in the geriatric patient population. Because of the increased prevalence of cardiovascular disease in the elderly, cautious use of Levothyroxine Sodium Injection in the elderly and in patients with known cardiac risk factors is advised. Atrial fibrillation is a common side effect associated with levothyroxine treatment in the elderly [see Dosage and Administration (2) and Warnings and Precautions (5) ].

8.6 Renal Impairment Serum creatinine and levothyroxine levels should be closely monitored in patients with severe renal impairment receiving intravenous levothyroxine with betadex sulfobutyl (SBECD) [See Clinical Pharmacology (12.3) ].

Risk Summary The clinical data in pregnant women treated with oral levothyroxine to treat hypothyroidism do not indicate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. There are no data available on the use of Levothyroxine Sodium Injection in pregnant women. There are risks to the mother and fetus associated with myxedema coma in pregnancy (see Clinical Considerations) . No developmental or reproductive toxicity studies in animals have been conducted with Levothyroxine Sodium Injection. The estimated background risks of major birth defects and miscarriage for the indicated populations are unknown. All pregnancies have background risks of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risks of major birth defects and miscarriage in clinically recognized pregnancies are 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk Myxedema coma is a medical emergency that can be fatal if left untreated. Delaying treatment in pregnant women with myxedema coma increases the risk of maternal and fetal morbidity and mortality. Life-sustaining therapy for pregnant women with myxedema coma should not be withheld due to potential concerns regarding the effects of Levothyroxine Sodium Injection on the fetus.

The safety and effectiveness of Levothyroxine Sodium Injection have not been established in pediatric patients.

Levothyroxine sodium injection contains synthetic levothyroxine (L-thyroxine) sodium salt. Levothyroxine sodium has an empirical formula of C 15 H 10 I 4 NNaO 4 , a molecular weight of 798.85 g/mol (anhydrous), and the following structural formula: Levothyroxine sodium injection is a sterile, preservative-free, clear, colorless to slightly yellow solution for intravenous administration available as 100 mcg/mL in a single-dose clear glass vial. Each mL of levothyroxine sodium injection also contains 0.05 mg arginine, USP; 80 mg betadex sulfobutyl ether sodium, USP; 0.05 mg edetate disodium, USP; and water for injection, USP. Sodium chloride, USP was added to adjust tonicity. Hydrochloric acid, NF and/or sodium hydroxide, NF may have been added for pH adjustment. chemical structure

12.1 Mechanism of Action Thyroid hormones exert their physiologic actions through control of DNA transcription and protein synthesis. Triiodothyronine (T 3 ) and levothyroxine (T 4 ) diffuse into the cell nucleus and bind to thyroid receptor proteins attached to DNA. This hormone nuclear receptor complex activates gene transcription and synthesis of messenger RNA and cytoplasmic proteins. The physiological actions of thyroid hormones are produced predominantly by T 3 , the majority of which (approximately 80%) is derived from T 4 by deiodination in peripheral tissues.

12.2 Pharmacodynamics Thyroid hormone synthesis and secretion is regulated by the hypothalamic pituitary-thyroid axis. Thyrotropin releasing hormone (TRH) released from the hypothalamus stimulates secretion of thyrotropin stimulating hormone (TSH) from the anterior pituitary. TSH, in turn, is the physiologic stimulus for the synthesis and secretion of thyroid hormones, T 4 and T 3 , by the thyroid gland. Circulating serum T 3 and T 4 levels exert a feedback effect on both TRH and TSH secretion. When serum T 3 and T 4 levels increase, TRH and TSH secretion decrease. When thyroid hormone levels decrease, TRH and TSH secretion increases. TSH is used for the diagnosis of hypothyroidism and evaluation of levothyroxine therapy adequacy with other laboratory and clinical data [see Dosage (2.1) ]. There are drugs known to affect thyroid hormones and TSH by various mechanisms and those examples are diazepam, ethioamide, lovastatin, metoclopramide, 6-mercaptopurine, nitroprusside, perphenazine, and thiazide diuretics. Some drugs may cause a transient decrease in TSH secretion without hypothyroidism and those drugs (dose) are dopamine (greater than 1 mcg per kg per min), glucocorticoids (hydrocortisone greater than 100 mg per day or equivalent) and octreotide (greater than 100 mcg per day). Thyroid hormones regulate multiple metabolic processes and play an essential role in normal growth and development, and normal maturation of the central nervous system and bone. The metabolic actions of thyroid hormones include augmentation of cellular respiration and thermogenesis, as well as metabolism of proteins, carbohydrates and lipids. The protein anabolic effects of thyroid hormones are essential to normal growth and development.

12.3 Pharmacokinetics Absorption – Levothyroxine Sodium Injection is administered via the intravenous route. Following administration, the synthetic levothyroxine cannot be distinguished from the natural hormone that is secreted endogenously. Distribution – Circulating thyroid hormones are greater than 99% bound to plasma proteins, including thyroxine binding globulin (TBG), thyroxine binding prealbumin (TBPA), and albumin (TBA), whose capacities and affinities vary for each hormone. The higher affinity of both TBG and TBPA for T 4 partially explains the higher serum levels, slower metabolic clearance, and longer half-life of T 4 compared to T 3 . Protein bound thyroid hormones exist in reverse equilibrium with small amounts of free hormone. Only unbound hormone is metabolically active. Many drugs and physiologic conditions affect the binding of thyroid hormones to serum proteins [see Warnings and Precautions (5) and Drug Interactions (7) ]. Thyroid hormones do not readily cross the placental barrier [see Warnings and Precautions (5) and Use in Specific Populations (8) ]. Betadex sulfobutyl ether (SBECD) does not affect levothyroxine binding to plasma proteins. Metabolism – T 4 is slowly eliminated. The major pathway of thyroid hormone metabolism is through sequential deiodination. Approximately eighty percent of circulating T 3 is derived from peripheral T 4 by mono-deiodination. The liver is the major site of degradation for both T 4 and T 3 , with T 4 deiodination also occurring at a number of additional sites, including the kidney and other tissues. Approximately 80% of the daily dose of T 4 is deiodinated to yield equal amounts of T 3 and reverse T 3 (rT 3 ). T 3 and rT 3 are further deiodinated to diiodothyronine. Thyroid hormones are also metabolized via conjugation with glucuronides and sulfates and excreted directly into the bile and gut where they undergo enterohepatic recirculation. Elimination – Thyroid hormones are primarily eliminated by the kidneys. A portion of the conjugated hormone reaches the colon unchanged, where it is hydrolyzed and eliminated in feces as the free hormones. Urinary excretion of T 4 decreases with age. In patients with severe renal impairment or ESRD (eGFR of < 15 mL/min/1.73 m2), accumulation of SBECD occurs [see Renal Impairment 8.6 ]. Table 1: Pharmacokinetic Parameters of Thyroid Hormones in Euthyroid Patients Hormone Ratio in Thyroglobulin Biologic Potency Half-Life (Days) Protein Binding (%) 2 T 4 10 to 20 1 6 to 8 1 99.96 T 3 1 4 ≤ 2 99.5 T 4 : Levothyroxine T 3 : Liothyronine 1 3 to 4 days in hyperthyroidism, 9 to 10 days in hypothyroidism. 2 Includes TBG, TBPA, and TBA.

Thyroid hormones exert their physiologic actions through control of DNA transcription and protein synthesis. Triiodothyronine (T 3 ) and levothyroxine (T 4 ) diffuse into the cell nucleus and bind to thyroid receptor proteins attached to DNA. This hormone nuclear receptor complex activates gene transcription and synthesis of messenger RNA and cytoplasmic proteins. The physiological actions of thyroid hormones are produced predominantly by T 3 , the majority of which (approximately 80%) is derived from T 4 by deiodination in peripheral tissues.

Thyroid hormone synthesis and secretion is regulated by the hypothalamic pituitary-thyroid axis. Thyrotropin releasing hormone (TRH) released from the hypothalamus stimulates secretion of thyrotropin stimulating hormone (TSH) from the anterior pituitary. TSH, in turn, is the physiologic stimulus for the synthesis and secretion of thyroid hormones, T 4 and T 3 , by the thyroid gland. Circulating serum T 3 and T 4 levels exert a feedback effect on both TRH and TSH secretion. When serum T 3 and T 4 levels increase, TRH and TSH secretion decrease. When thyroid hormone levels decrease, TRH and TSH secretion increases. TSH is used for the diagnosis of hypothyroidism and evaluation of levothyroxine therapy adequacy with other laboratory and clinical data [see Dosage (2.1) ]. There are drugs known to affect thyroid hormones and TSH by various mechanisms and those examples are diazepam, ethioamide, lovastatin, metoclopramide, 6-mercaptopurine, nitroprusside, perphenazine, and thiazide diuretics. Some drugs may cause a transient decrease in TSH secretion without hypothyroidism and those drugs (dose) are dopamine (greater than 1 mcg per kg per min), glucocorticoids (hydrocortisone greater than 100 mg per day or equivalent) and octreotide (greater than 100 mcg per day). Thyroid hormones regulate multiple metabolic processes and play an essential role in normal growth and development, and normal maturation of the central nervous system and bone. The metabolic actions of thyroid hormones include augmentation of cellular respiration and thermogenesis, as well as metabolism of proteins, carbohydrates and lipids. The protein anabolic effects of thyroid hormones are essential to normal growth and development.

Absorption – Levothyroxine Sodium Injection is administered via the intravenous route. Following administration, the synthetic levothyroxine cannot be distinguished from the natural hormone that is secreted endogenously. Distribution – Circulating thyroid hormones are greater than 99% bound to plasma proteins, including thyroxine binding globulin (TBG), thyroxine binding prealbumin (TBPA), and albumin (TBA), whose capacities and affinities vary for each hormone. The higher affinity of both TBG and TBPA for T 4 partially explains the higher serum levels, slower metabolic clearance, and longer half-life of T 4 compared to T 3 . Protein bound thyroid hormones exist in reverse equilibrium with small amounts of free hormone. Only unbound hormone is metabolically active. Many drugs and physiologic conditions affect the binding of thyroid hormones to serum proteins [see Warnings and Precautions (5) and Drug Interactions (7) ]. Thyroid hormones do not readily cross the placental barrier [see Warnings and Precautions (5) and Use in Specific Populations (8) ]. Betadex sulfobutyl ether (SBECD) does not affect levothyroxine binding to plasma proteins. Metabolism – T 4 is slowly eliminated. The major pathway of thyroid hormone metabolism is through sequential deiodination. Approximately eighty percent of circulating T 3 is derived from peripheral T 4 by mono-deiodination. The liver is the major site of degradation for both T 4 and T 3 , with T 4 deiodination also occurring at a number of additional sites, including the kidney and other tissues. Approximately 80% of the daily dose of T 4 is deiodinated to yield equal amounts of T 3 and reverse T 3 (rT 3 ). T 3 and rT 3 are further deiodinated to diiodothyronine. Thyroid hormones are also metabolized via conjugation with glucuronides and sulfates and excreted directly into the bile and gut where they undergo enterohepatic recirculation. Elimination – Thyroid hormones are primarily eliminated by the kidneys. A portion of the conjugated hormone reaches the colon unchanged, where it is hydrolyzed and eliminated in feces as the free hormones. Urinary excretion of T 4 decreases with age. In patients with severe renal impairment or ESRD (eGFR of < 15 mL/min/1.73 m2), accumulation of SBECD occurs [see Renal Impairment 8.6 ]. Table 1: Pharmacokinetic Parameters of Thyroid Hormones in Euthyroid Patients Hormone Ratio in Thyroglobulin Biologic Potency Half-Life (Days) Protein Binding (%) 2 T 4 10 to 20 1 6 to 8 1 99.96 T 3 1 4 ≤ 2 99.5 T 4 : Levothyroxine T 3 : Liothyronine 1 3 to 4 days in hyperthyroidism, 9 to 10 days in hypothyroidism. 2 Includes TBG, TBPA, and TBA.

, Mutagenesis, Impairment of Fertility Animal studies have not been performed to evaluate the carcinogenic potential, mutagenic potential or effects on fertility of Levothyroxine Sodium Injection.