Levothyroxine Sodium (Page 2 of 4)

7.4 Antidepressant Therapy

Concurrent use of tricyclic (e.g., amitriptyline) or tetracyclic (e.g., maprotiline) antidepressants and levothyroxine may increase the therapeutic and toxic effects of both drugs, possibly due to increased receptor sensitivity to catecholamines. Toxic effects may include increased risk of cardiac arrhythmias and CNS stimulation; onset of action of tricyclics may be accelerated. Administration of sertraline in patients stabilized on levothyroxine may result in increased levothyroxine requirements.

7.5 Ketamine

Concurrent use may produce marked hypertension and tachycardia; cautious administration to patients receiving thyroid hormone therapy is recommended.

7.6 Sympathomimetics

Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.

7.7 Drug-Laboratory Test Interactions

Changes in thyroxine binding globulin (TBG) concentration must be considered when interpreting levothyroxine and triiodothyronine values, which necessitates measurement and evaluation of unbound (free) hormone and/or determination of the free levothyroxine index. Pregnancy, infectious hepatitis, estrogens, estrogen containing oral contraceptives, and acute intermittent porphyria increase TBG concentrations. Decreases in TBG concentrations are observed in nephrosis, severe hypoproteinemia, severe liver disease, acromegaly, and after androgen or corticosteroid therapy. Familial hyper or hypo thyroxine binding globulinemias have been described, with the incidence of TBG deficiency approximating 1 in 9000.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category A – There are no reported cases of Levothyroxine Sodium for Injection used to treat myxedema coma in patients who were pregnant or lactating. Studies in pregnant women treated with oral levothyroxine to maintain a euthyroid state have not shown an increased risk of fetal abnormalities. Therefore, pregnant patients who develop myxedema should be treated with Levothyroxine Sodium for Injection as the risk of nontreatment is associated with a high probability of significant morbidity or mortality to the maternal patient and the fetus.

8.2 Labor and Delivery

Patients in labor who develop myxedema have not been reported in the literature. However, patients should be treated with Levothyroxine Sodium for Injection as the risk of nontreatment is associated with a high probability of significant morbidity or mortality to the maternal patient and the fetus.

8.3 Nursing Mothers

Adequate replacement doses of thyroid hormones are required to maintain normal lactation. There are no reported cases of Levothyroxine Sodium for Injection used to treat myxedema coma in patients who are lactating. However, such patients should be treated with Levothyroxine Sodium for Injection as the risk of nontreatment is associated with a high probability of significant morbidity or mortality to the nursing patient.

8.4 Pediatric Use

Myxedema coma is a disease of the elderly. An approved, oral dosage form of levothyroxine should be used in the pediatric patient population for maintaining a euthyroid state in non-complicated hypothyroidism.

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 for 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)].

10 OVERDOSAGE

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 for Injection (greater than 500 mcg) are associated with cardiac complications in patients with underlying cardiac disease.

Treatment of Overdosage

Levothyroxine Sodium for 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.

11 DESCRIPTION

Levothyroxine Sodium for Injection contains synthetic crystalline 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:

structure

Levothyroxine Sodium for Injection is a sterile, preservative-free lyophilized powder consisting of the active ingredient, levothyroxine sodium, and the excipients dibasic sodium phosphate heptahydrate, USP; mannitol, USP; and sodium hydroxide, NF in single dose amber glass vials. Levothyroxine Sodium for Injection is available at three dosage strengths: 100 mcg per vial, 200 mcg per vial and 500 mcg per vial.

12 CLINICAL PHARMACOLOGY

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, ethionamide, 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.

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2024. All Rights Reserved.