Proloid S

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Proloid S uses

Proloid S consists of Levothyroxine Sodium, Liothyronine Sodium.

Levothyroxine Sodium:


1 INDICATIONS AND USAGE

Proloid S (Levothyroxine Sodium) for Injection is indicated for the treatment of myxedema coma. Important Limitations of Use: The relative bioavailability between Proloid S (Levothyroxine Sodium) for Injection and oral levothyroxine products has not been established. Caution should be used when switching patients from oral levothyroxine products to Proloid S (Levothyroxine Sodium) for Injection as accurate dosing conversion has not been studied.

Proloid S (Levothyroxine Sodium) is an L-thyroxine product. Levothyroxine (T4) Sodium for Injection is indicated for the treatment of myxedema coma. (1)

Important Limitations of Use:

The relative bioavailability of this drug has not been established. Use caution when converting patients from oral to intravenous levothyroxine.

2 DOSAGE AND ADMINISTRATION

  • An initial intravenous loading dose of Proloid S 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. ( 2.1 )
  • Reconstitute the lyophilized Proloid S (Levothyroxine Sodium) for Injection by aseptically adding 5 mL of 0.9% Sodium Chloride Injection, USP. Shake vial to ensure complete mixing. Reconstituted drug product is preservative free. Use immediately after reconstitution. Discard any unused portion. ( 2.3 )
  • Do not add to other IV fluids. ( 2.3 )

2.1 Dosage

An initial intravenous loading dose of Proloid S (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 Proloid S (Levothyroxine Sodium) for Injection.

Proloid S (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 Proloid S (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 Proloid S (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 Proloid S (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 Proloid S (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 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 Proloid S (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.

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3 DOSAGE FORMS AND STRENGTHS

Proloid S (Levothyroxine Sodium) for Injection is supplied as a lyophilized powder at three strengths in single use amber-colored vials: 100 mcg, 200 mcg and 500 mcg.

Lyophilized powder for injection in single use vials: 100 mcg, 200 mcg and 500 mcg. ( 3 )

4 CONTRAINDICATIONS

None.

None.

5 WARNINGS AND PRECAUTIONS

  • Excessive bolus doses of Proloid S for Injection (> 500 mcg) are associated with cardiac complications, particularly in the elderly and in patients with an underlying cardiac condition. Initiate therapy with doses at the lower end of the recommended range. ( 5.1 )
  • Close observation of the patient following the administration of Proloid S (Levothyroxine Sodium) for Injection is advised. ( 5.1 )
  • Proloid S (Levothyroxine Sodium) for Injection therapy for patients with previously undiagnosed endocrine disorders, including adrenal insufficiency, hypopituitarism, and diabetes insipidus, may worsen symptoms of these endocrinopathies. ( 5.2 )

5.1 Risk of Cardiac Complications in Elderly and in Patients with Cardiovascular Disease

Excessive bolus dosing of Proloid S (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 Proloid S (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 Proloid S (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 Proloid S 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 Proloid S (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 Proloid S (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 .

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6 ADVERSE REACTIONS

Excessive 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.

Excessive doses of L-thyroxine can predispose to signs and symptoms compatible with hyperthyroidism.


To report SUSPECTED ADVERSE REACTIONS, contact Fresenius Kabi USA, LLC, Medical Affairs Department at 1-800-551-7176 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

7 DRUG INTERACTIONS

Many drugs affect thyroid hormone pharmacokinetics and metabolism and may alter the therapeutic response to Proloid S (Levothyroxine Sodium) for Injection. In addition, thyroid hormones and thyroid status have varied effects on the pharmacokinetics and actions of other drugs.

Many drugs affect thyroid hormone pharmacokinetics and metabolism (e.g., absorption, synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to Proloid S (Levothyroxine Sodium) for Injection. ( 7 , 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 Proloid S 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.

7.4 Antidepressant Therapy

Concurrent use of tricyclic 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.

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8 USE IN SPECIFIC POPULATIONS

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

8.1 Pregnancy

Pregnancy Category A – There are no reported cases of Proloid S (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 Proloid S (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 Proloid S 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 Proloid S (Levothyroxine Sodium) for Injection used to treat myxedema coma in patients who are lactating. However, such patients should be treated with Proloid S (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 Proloid S (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 )].

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

Treatment of Overdosage

Proloid S (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

Proloid S (Levothyroxine Sodium) for Injection contains synthetic crystalline levothyroxine (L-thyroxine) sodium salt. Levothyroxine sodium has an empirical formula of C15H10I4NNaO4, a molecular weight of 798.85 g/mol (anhydrous), and the following structural formula:



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

structure

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Thyroid hormones exert their physiologic actions through control of DNA transcription and protein synthesis. Triiodothyronine and levothyroxine (T4) 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 T3, the majority of which (approximately 80%) is derived from T4 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, T4 and T3, by the thyroid gland. Circulating serum T3 and T4 levels exert a feedback effect on both TRH and TSH secretion. When serum T3 and T4 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 . 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 – Proloid S (Levothyroxine Sodium) for 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 T4 partially explains the higher serum levels, slower metabolic clearance, and longer half life of T4 compared to T3. 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 . Thyroid hormones do not readily cross the placental barrier .

Metabolism – T4 is slowly eliminated. The major pathway of thyroid hormone metabolism is through sequential deiodination. Approximately eighty percent of circulating T3 is derived from peripheral T4 by monodeiodination. The liver is the major site of degradation for both T4 and T3, with T4 deiodination also occurring at a number of additional sites, including the kidney and other tissues. Approximately 80% of the daily dose of T4 is deiodinated to yield equal amounts of T3 and reverse T3 (r T3). T3 and r T3 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 T4 decreases with age.

Table 1: Pharmacokinetic Parameters of Thyroid Hormones in Euthyroid Patients


Hormone


Ratio in

Thyroglobulin


Biologic

Potency


Half-Life

(Days)


Protein

Binding

(%)2


T4


10 to 20


1


6 to 81


99.96


T3


1


4


≤ 2


99.5


T4: Levothyroxine

T3: Liothyronine

1 3 to 4 days in hyperthyroidism, 9 to 10 days in hypothyroidism.

2 Includes TBG, TBPA, and TBA.

Drug Interactions

A listing of drug interaction with T4 is provided in the following tables, although it may not be comprehensive due to the introduction of new drugs that interact with the thyroidal axis or the discovery of previously unknown interactions. The prescriber should be aware of this fact and should consult appropriate reference sources (e.g., package inserts of newly approved drugs, medical literature) for additional information if a drug-drug interaction with levothyroxine is suspected.

Table 2: Drugs That May Alter T4 and T3 Serum Transport Without Affecting free T4 Concentration (Euthyroidism)


Drugs That May Increase Serum TBG Concentration


Drugs That May Decrease Serum TBG Concentration



Clofibrate

Estrogen-containing oral contraceptives

Estrogens (oral)

Heroin / Methadone

5-Fluorouracil

Mitotane

Tamoxifen


Androgens / Anabolic Steroids

Asparaginase

Glucocorticoids

Slow-Release Nicotinic Acid


Drugs That May Cause Protein-Binding Site Displacement

Potential impact : Administration of these agents with levothyroxine results in an initial transient increase in FT4. Continued administration results in a decrease in serum T4 and normal FT4 and TSH concentrations and, therefore, patients are clinically euthyroid.


Salicylates (> 2 g/day)


Salicylates inhibit binding of T4 and T3 to TBG and transthyretin. An initial increase in serum FT4 is followed by return of FT4 to normal levels with sustained therapeutic serum salicylate concentrations, although total-T4 levels may decrease by as much as 30%.


Other drugs:

Furosemide (> 80 mg IV)

Heparin

Hydantoins

Non-Steroidal Anti-inflammatory Drugs

- Fenamates

- Phenylbutazone




Table 3: Drugs That May Alter Hepatic Metabolism of T4 (Hypothyroidism)

Potential impact: Stimulation of hepatic microsomal drug-metabolizing enzyme activity may cause increased hepatic degradation of levothyroxine, resulting in increased levothyroxine requirements.


Drug or Drug Class



Carbamazepine

Hydantoins


Phenytoin and carbamazepine reduce serum protein binding of levothyroxine, and total- and free- T4 may be reduced by 20% to 40%, but most patients have normal serum TSH levels and are clinically euthyroid.


Other drugs:

Phenobarbital

Rifampin




Table 4: Drugs That May Decrease Conversion of T4 to T3

Potential impact: Administration of these enzyme inhibitors decreases the peripheral conversion of T4 to T3, leading to decreased T3 levels. However, serum T4 levels are usually normal but may occasionally be slightly increased.


Drug or Drug Class


Effect


Beta-adrenergic antagonists

(e.g. Propranolol > 160 mg/day)


In patients treated with large doses of propranolol (> 160 mg/day), T3 and T4 levels change slightly, TSH levels remain normal, and patients are clinically euthyroid. It should be noted that actions of particular beta-adrenergic antagonists may be impaired when the hypothyroid patient is converted to the euthyroid state.


Glucocorticoids

(e.g. Dexamethasone > 4 mg/day)



Short-term administration of large doses of glucocorticoids may decrease serum T3 concentrations by 30% with minimal change in serum T4 levels. However, long-term glucocorticoid therapy may result in slightly decreased T3 and T4 levels due to decreased TBG production.


Other drug:

Amiodarone



13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Animal studies have not been performed to evaluate the carcinogenic potential, mutagenic potential or effects on fertility of Proloid S for Injection.

13.2 Animal Toxicology and Pharmacology

No animal toxicology studies have been conducted with Proloid S (Levothyroxine Sodium) for Injection.

14 CLINICAL STUDIES

No clinical studies have been conducted with Proloid S (Levothyroxine Sodium) for Injection in patients with myxedema coma. However, data from published literature support the intravenous use of Proloid S (Levothyroxine Sodium) for the treatment of myxedema coma.

16 HOW SUPPLIED/STORAGE AND HANDLING

16.1 How Supplied

Proloid S for Injection is available in three dosage strengths.

Product

No.

NDC

No.


Strength


Reconstituted

Concentration

506107

63323-649-07


100 mcg/vial


20 mcg/mL

506247

63323-647-10

200 mcg/vial

40 mcg/mL

506248

63323-648-10


500 mcg/vial


100 mcg/mL


16.2 Storage and Handling

Protect from light and store dry product at 20° to 25°C (68° to 77°F). Reconstituted drug product is preservative free. Discard any unused portion.

This container closure is not made with natural rubber latex.

451253C

Revised: April 2013


PACKAGE LABEL - PRINCIPAL DISPLAY - Levothyroxine 100 mcg Single Use Vial Label

NDC 63323-649-07

506107

Proloid S (Levothyroxine Sodium) for Injection

100 mcg/vial

For Intravenous Use

Single Use Vial

Discard any unused portion.

Rx only




PACKAGE LABEL - PRINCIPAL DISPLAY - Levothyroxine 100 mcg Single Use Vial Carton Panel

NDC 63323-649-07

506107

Proloid S (Levothyroxine Sodium) for Injection

100 mcg/vial

For Intravenous Use

Single Use Vial

Discard any unused portion.

Rx only




P ACKAGE LABEL - PRINCIPAL DISPLAY - Levothyroxine 500 mcg Single Use Vial Label

NDC 63323-648-10

506248

Proloid S (Levothyroxine Sodium) for Injection

500 mcg/vial

For Intravenous Use

Single Use Vial

Discard any unused portion.

Rx only



P ACKAGE LABEL - PRINCIPAL DISPLAY - Levothyroxine 500 mcg Single Use Vial Carton Panel

NDC 63323-648-10

506248

Proloid S (Levothyroxine Sodium) for Injection

500 mcg/vial

For Intravenous Use

Single Use Vial

Discard any unused portion.

Rx only



P ACKAGE LABEL - PRINCIPAL DISPLAY - Levothyroxine 200 mcg Single Use Vial Label

NDC 63323-647-10

506247

Proloid S (Levothyroxine Sodium) for Injection

200 mcg/vial

For Intravenous Use

Single Use Vial

Discard any unused portion.

Rx only


P ACKAGE LABEL - PRINCIPAL DISPLAY - Levothyroxine 200 mcg Single Use Vial Carton Label

NDC 63323-647-10

506247

Proloid S (Levothyroxine Sodium) for Injection

200 mcg/vial

For Intravenous Use

Single Use Vial

Discard any unused portion.

Rx only

logo 506107-vial 506107-box 506248-vial 506248-box 506247-vial 506247-box

Liothyronine Sodium:


INDICATIONS AND USAGE

Proloid S Tablets are indicated:

  • As replacement or supplemental therapy in patients with hypothyroidism of any etiology, except transient hypothyroidism during the recovery phase of subacute thyroiditis. This category includes cretinism, myxedema, and ordinary hypothyroidism in patients of any age (children, adults, the elderly), or state (including pregnancy); primary hypothyroidism resulting from functional deficiency, primary atrophy, partial or total absence of thyroid gland, or the effects of surgery, radiation, or drugs, with or without the presence of goiter; and secondary (pituitary), or tertiary (hypothalamic) hypothyroidism.
  • As pituitary TSH suppressants, in the treatment or prevention of various types of euthyroid goiters, including thyroid nodules, sub-acute or chronic Iymphocytic thyroiditis (Hashimoto's), multinodular goiter, and in the management of thyroid cancer.

CONTRAINDICATIONS

Thyroid hormone preparations are generally contraindicated in patients with diagnosed but as yet uncorrected adrenal cortical insufficiency, untreated thyrotoxicosis, and apparent hypersensitivity to any of their active or extraneous constituents. There is no well documented evidence from the literature, however, of true allergic or idiosyncratic reactions to thyroid hormone.

WARNINGS

Drugs with thyroid hormone activity, alone or together with other therapeutic agents, have been used for the treatment of obesity. 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.

The use of thyroid hormones in the therapy of obesity, alone or combined with other drugs, is unjustified and has been shown to be ineffective. Neither is their use justified for the treatment of male or female infertility unless this condition is accompanied by hypothyroidism.

PRECAUTIONS

General-Thyroid hormones should be used with great caution in a number of circumstances where the integrity of the cardiovascular system, particularly the coronary arteries, is suspected. These include patients with angina pectoris or the elderly, in whom there is a greater likelihood of occult cardiac disease. In these patients therapy should be initiated with low doses, i.e., one tablet of Proloid S (Liothyronine Sodium) ½ or Proloid S (Liothyronine Sodium) ¼. When, in such patients, a euthyroid state can only be reached at the expense of an aggravation of the cardiovascular disease, thyroid hormone dosage should be reduced.

Thyroid hormone therapy in patients with concomitant diabetes mellitus or diabetes insipidus or adrenal cortical insufficiency aggravates the intensity of their symptoms. Appropriate adjustments of the various therapeutic measures directed at these concomitant endocrine diseases are required. The therapy of myxedema coma requires simultaneous administration of glucocorticoids.

Hypothyroidism decreases and hyperthyroidism increases the sensitivity to oral anticoagulants. Prothrombin time should be closely monitored in thyroid treated patients on oral anticoagulants and dosage of the latter agents adjusted on the basis of frequent prothrombin time determinations. In infants, excessive doses of thyroid hormone preparations may produce craniosynostosis.

Information for the Patient-Patients on thyroid hormone 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.
  • They should immediately report during the course of therapy 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.
  • In case of concomitant diabetes mellitus, the daily dosage of antidiabetic medication may need readjustment as thyroid hormone replacement is achieved. If thyroid medication is stopped, a downward readjustment of the dosage of insulin or oral hypoglycemic agent may be necessary to avoid hypoglycemia. At all times, close monitoring of urinary glucose levels is mandatory in such patients.
  • In case of concomitant oral anticoagulant therapy, the prothrombin time should be measured frequently to determine if the dosage of oral anticoagulants is to be readjusted.
  • 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 usually the rule.
  • Tablets should be stored at cold temperature, between 36°F and 46°F (2°C and 8°C) in a tight, light-resistant container.

Laboratory Tests-Treatment of patients with thyroid hormones requires the periodic assessment of thyroid status by means of appropriate laboratory tests besides the full clinical evaluation. The TSH suppression test can be used to test the effectiveness of any thyroid preparation bearing in mind the relative insensitivity of the infant pituitary to the negative feedback effect of thyroid hormones. Serum T4 levels can be used to test the effectiveness of all thyroid medications except T3. When the total serum T4 is low but TSH is normal, a test specific to assess unbound (free) T4 levels is warranted. Specific measurements of T4 and T3 by competitive protein binding or radioimmunoassay are not influenced by blood levels of organic or inorganic iodine.

Drug Interactions-Oral Anticoagulants-Thyroid hormones appear to increase catabolism of vitamin K-dependent clotting factors. If oral anticoagulants are also being given, compensatory increases in clotting factor synthesis are impaired. Patients stabilized on oral anticoagulants who are found to require thyroid replacement therapy should be watched very closely when thyroid is started. If a patient is truly hypothyroid, it is likely that a reduction in anticoagulant dosage will be required. No special precautions appear to be necessary when oral anticoagulant therapy is begun in a patient already stabilized on maintenance thyroid replacement therapy.

Insulin or Oral Hypoglycemics-Initiating thyroid replacement therapy may cause increases in insulin or oral hypoglycemic requirements. The effects seen are poorly understood and depend upon a variety of factors such as dose and type of thyroid preparations and endocrine status of the patient. Patients receiving insulin or oral hypoglycemics should be closely watched during initiation of thyroid replacement therapy.

Cholestyramine or Colestipol-Cholestyramine or colestipol binds both T4 and T3 in the intestine thus impairing absorption of these thyroid hormones. In vitro studies indicate that the binding is not easily removed. Therefore, four to five hours should elapse between administration of cholestyramine or colestipol and thyroid hormones.

Estrogen, Oral Contraceptives-Estrogens tend to increase serum thyroxine-binding globulin (TBg). In a patient with a nonfunctioning thyroid gland who is receiving thyroid replacement therapy, free levothyroxine may be decreased when estrogens are started, thus increasing thyroid requirements. However, if the patient's thyroid gland has sufficient function, the decreased free thyroxine will result in a compensatory increase in thyroxine output by the thyroid. Therefore, patients without a functioning thyroid gland who are on thyroid replacement therapy may need to increase their thyroid dose if estrogens or estrogen-containing oral contraceptives are given.

Drug/Laboratory Test Interactions-The following drugs or moieties are known to interfere with laboratory tests performed in patients on thyroid hormone therapy: androgens, corticosteroids, estrogens, oral contraceptives containing estrogens, iodine-containing preparations, and the numerous preparations containing salicylates.

  • Changes in TBg concentration should be taken into consideration in the interpretation of T4 and T3 values. In such cases, the unbound (free) hormone should be measured. Pregnancy, estrogens, and estrogen-containing oral contraceptives increase TBg concentrations. TBg may also be increased during infectious hepatitis. Decreases in TBg concentrations are observed in nephrosis, acromegaly, and after androgen or corticosteroid therapy. Familial hyper- or hypothyroxine-binding-globulinemias have been described. The incidence of TBg deficiency approximates 1 in 9,000. The binding of thyroxine by TBPA is inhibited by salicylates.
  • Medicinal or dietary iodine interferes with all in vivo tests of radio-iodine uptake, producing low uptakes which may not be relative of a true decrease in hormone synthesis.
  • The persistence of clinical and laboratory evidence of hypothyroidism in spite of adequate dosage replacement indicates either poor patient compliance, poor absorption, excessive fecal loss, or inactivity of the preparation. Intracellular resistance to thyroid hormone is quite rare.

Carcinogenesis, Mutagenesis, and Impairment of Fertility-A reportedly apparent association between prolonged thyroid therapy and breast cancer has not been confirmed and patients on thyroid for established indications should not discontinue therapy. No confirmatory long-term studies in animals have been performed to evaluate carcinogenic potential, mutagenicity, or impairment of fertility in either males or females.

Pregnancy-Category A-Thyroid hormones do not readily cross the placental barrier. The clinical experience to date does not indicate any adverse effect on fetuses when thyroid hormones are administered to pregnant women. On the basis of current knowledge, thyroid replacement therapy to hypothyroid women should not be discontinued during pregnancy.

Nursing Mothers-Minimal amounts of thyroid hormones are excreted in human milk. Thyroid is not associated with serious adverse reactions and does not have a known tumorigenic potential. However, caution should be exercised when thyroid is administered to a nursing woman.

Pediatric Use-Pregnant mothers provide little or no thyroid hormone to the fetus. The incidence of congenital hypothyroidism is relatively high (1:4000) and the hypothyroid fetus would not derive any benefit from the small amounts of hormone crossing the placental barrier. Routine determinations of serum (T4) and/or TSH is strongly advised in neonates in view of the deleterious effects of thyroid deficiency on growth and development.

Treatment should be initiated immediately upon diagnosis, and maintained for life, unless transient hypothyroidism is suspected; in which case, therapy may be interrupted for 2 to 8 weeks after the age of 3 years to reassess the condition. Cessation of therapy is justified in patients who have maintained a normal TSH during those 2 to 8 weeks.

ADVERSE REACTIONS

During postmarketing surveillance, the following events have been observed to have occured in patients administered Proloid S (Liothyronine Sodium): fatigue, sluggishness, increase in weight, alopecia, palpitations, dry skin, urticaria, headache, hyperhidrosis, pruritus, asthenia, increased blood pressure, arthralgia, myalgia, tremor, hypothyroidism, increase in TSH, decrease in TSH, nausea, chest pain, hypersensitivity, keratoconjunctivitis sicca, increased heart rate, irregular heart rate, anxiety, depression, and insomnia.

Adverse reactions other than those indicative of hyperthyroidism because of therapeutic overdosage, either initially or during the maintenance period, are rare.

OVERDOSAGE

Signs and Symptoms-Excessive doses of thyroid result in a hypermetabolic state resembling in every respect the condition of endogenous origin. The condition may be self-induced.

Treatment of Overdosage-Dosage should be reduced or therapy temporarily discontinued if signs and symptoms of overdosage appear.

Treatment may be reinstituted at a lower dosage. In normal individuals, normal hypothalamic-pituitary-thyroid axis function is restored in 6 to 8 weeks after thyroid suppression.

Treatment of acute massive thyroid hormone overdosage is aimed at reducing gastrointestinal absorption of the drugs and counteracting central and peripheral effects, mainly those of increased sympathetic activity. Vomiting may be induced initially if further gastrointestinal absorption can reasonably be prevented and barring contraindications such as coma, convulsions, or loss of the gagging reflex. Treatment is symptomatic and supportive. Oxygen may be administered and ventilation maintained. Cardiac glycosides may be indicated if congestive heart failure develops. Measures to control fever, hypoglycemia, or fluid loss should be instituted if needed. Antiadrenergic agents, particularly propranolol, have been used advantageously in the treatment of increased sympathetic activity. Propranolol may be administered intravenously at a dosage of 1 to 3 mg over a 10 minute period or orally, 80 to 160 mg/day, initially, especially when no contraindications exist for its use.

DOSAGE AND ADMINISTRATION

The dosage of Proloid S (Liothyronine Sodium) Tablets (Liotrix Tablets, USP) is determined by the indication and must in every case be individualized according to patient response and laboratory findings.

Thyroid hormones are given orally. In acute, emergency conditions, injectable sodium levothyroxine may be given intravenously when oral administration is not feasible or desirable, as in the treatment of myxedema coma, or during total parenteral nutrition. Intramuscular administration is not advisable because of reported poor absorption.

Hypothyroidism-Therapy is usually instituted using low doses with increments which depend on the cardiovascular status of the patient. The usual starting dose is one tablet of Proloid S (Liothyronine Sodium) ½ with increments of one tablet of Proloid S (Liothyronine Sodium) ¼ every 2 to 3 weeks. A lower starting dosage, one tablet of Proloid S (Liothyronine Sodium) ¼/day, is recommended in patients with long-standing myxedema, particularly if cardiovascular impairment is suspected, in which case extreme caution is recommended. The appearance of angina is an indication for a reduction in dosage. Most patients require one tablet of Proloid S (Liothyronine Sodium) 1 to one tablet of Proloid S (Liothyronine Sodium) 2 per day. Failure to respond to doses of one tablet of Proloid S (Liothyronine Sodium) 3 suggests lack of compliance or malabsorption. Maintenance dosages of one tablet of Proloid S (Liothyronine Sodium) 1 to one tablet of Proloid S (Liothyronine Sodium) 2 per day usually result in normal serum levothyroxine (T4) and triiodothyronine (T3) levels. Adequate therapy usually results in normal TSH and T4 levels after 2 to 3 weeks of therapy.

Readjustment of thyroid hormone dosage should be made within the first four weeks of therapy, after proper clinical and laboratory evaluations, including serum levels of T4, bound and free, and TSH.

T3 may be used in preference to levothyroxine (T4) during radio-isotope scanning procedures, since induction of hypothyroidism in those cases is more abrupt and can be of shorter duration. It may also be preferred when impairment of peripheral conversion of T4 and T3 is suspected.

Myxedema Coma-Myxedema coma is usually precipitated in the hypothyroid patient of long-standing by intercurrent illness or drugs such as sedatives and anesthetics and should be considered a medical emergency. Therapy should be directed at the correction of electrolyte disturbances and possible infection besides the administration of thyroid hormones. Corticosteroids should be administered routinely. T4 and T3 may be administered via a nasogastric tube but the preferred route of administration of both hormones is intravenous. Sodium levothyroxine (T4) is given at a starting dose of 400 mcg (100 mcg/mL) given rapidly, and is usually well tolerated, even in the elderly. This initial dose is followed by daily supplements of 100 to 200 mcg given IV. Normal T4 levels are achieved in 24 hours followed in 3 days by threefold elevation of T3. Oral therapy with thyroid hormone would be resumed as soon as the clinical situation has been stabilized and the patient is able to take oral medication.

Thyroid Cancer-Exogenous thyroid hormone may produce regression of metastases from follicular and papillary carcinoma of the thyroid and is used as ancillary therapy of these conditions with radioactive iodine. TSH should be suppressed to low or undetectable levels. Therefore, larger amounts of thyroid hormone than those used for replacement therapy are required. Medullary carcinoma of the thyroid is usually unresponsive to this therapy.

Thyroid Suppression Therapy-Administration of thyroid hormone in doses higher than those produced physiologically by the gland results in suppression of the production of endogenous hormone. This is the basis for the thyroid suppression test and is used as an aid in the diagnosis of patients with signs of mild hyperthyroidism in whom baseline laboratory tests appear normal, or to demonstrate thyroid gland autonomy in patients with Grave's ophthalmopathy. 131I uptake is determined before and after the administration of the exogenous hormone. A fifty percent or greater suppression of uptake indicates a normal thyroid-pituitary axis and thus rules out thyroid gland autonomy.

For adults, the usual suppressive dose of levothyroxine (T4) is 1.56 mcg/kg of body weight per day given for 7 to 10 days. These doses usually yield normal serum T4 and T3 levels and lack of response to TSH.

Thyroid hormones should be administered cautiously to patients in whom there is strong suspicion of thyroid gland autonomy, in view of the fact that the exogenous hormone effects will be additive to the endogenous source.

Pediatric Dosage-Pediatric dosage should follow the recommendations summarized in Table 1. In infants with congenital hypothyroidism, therapy with full doses should be instituted as soon as the diagnosis has been made.

Age T3/T4 to T3/T4
0-6 mos 3.1/12.5 to 6.25/25
6-12 mos 6.25/25 to 9.35/37.5
1-5 yrs 9.35/37.5 to 12.5/50
6-12 yrs 12.5/50 to 18.75/75
Over 12 yrs over 18.75/75

HOW SUPPLIED

Proloid S (Liothyronine Sodium) Tablets (Liotrix Tablets, USP) are available in five potencies coded as follows:

Composition
Name (T3/T4 per tablet) Color Armacode® NDC
Thyrolar-1/4 3.1 mcg/ 12.5 mcg Violet/White YC 0456-0040-01
Thyrolar-1/2 6.25 mcg/ 25 mcg Peach/White YD 0456-0045-01
Thyrolar-1 12.5 mcg/ 50 mcg Pink/White YE 0456-0050-01
Thyrolar-2 25 mcg/ 100 mcg Green/White YF 0456-0055-01
Thyrolar-3 37.5 mcg/ 150 mcg Yellow/White YH 0456-0060-01

Supplied in bottles of 100, two-layered compressed tablets.

Tablets should be stored at cold temperature, between 36˚F and 46˚F (2˚C and 8˚C) in a tight, light-resistant container.

Note: (T3 Proloid S (Liothyronine Sodium) sodium is approximately four times as potent as T4 thyroxine on a microgram for microgram basis.)

FOREST PHARMACEUTICALS, INC.

A Subsidiary of Forest Laboratories, Inc.

St. Louis, MO 63045

Rev. January 2010

RMC #1436

© 2010 Forest Laboratories, Inc.

Proloid S pharmaceutical active ingredients containing related brand and generic drugs:

Active ingredient is the part of the drug or medicine which is biologically active. This portion of the drug is responsible for the main action of the drug which is intended to cure or reduce the symptom or disease. The other portions of the drug which are inactive are called excipients; there role is to act as vehicle or binder. In contrast to active ingredient, the inactive ingredient's role is not significant in the cure or treatment of the disease. There can be one or more active ingredients in a drug.


Proloid S available forms, composition, doses:

Form of the medicine is the form in which the medicine is marketed in the market, for example, a medicine X can be in the form of capsule or the form of chewable tablet or the form of tablet. Sometimes same medicine can be available as injection form. Each medicine cannot be in all forms but can be marketed in 1, 2, or 3 forms which the pharmaceutical company decided based on various background research results.
Composition is the list of ingredients which combinedly form a medicine. Both active ingredients and inactive ingredients form the composition. The active ingredient gives the desired therapeutic effect whereas the inactive ingredient helps in making the medicine stable.
Doses are various strengths of the medicine like 10mg, 20mg, 30mg and so on. Each medicine comes in various doses which is decided by the manufacturer, that is, pharmaceutical company. The dose is decided on the severity of the symptom or disease.


Proloid S destination | category:

Destination is defined as the organism to which the drug or medicine is targeted. For most of the drugs what we discuss, human is the drug destination.
Drug category can be defined as major classification of the drug. For example, an antihistaminic or an antipyretic or anti anginal or pain killer, anti-inflammatory or so.


Proloid S Anatomical Therapeutic Chemical codes:

A medicine is classified depending on the organ or system it acts [Anatomical], based on what result it gives on what disease, symptom [Therapeutical], based on chemical composition [Chemical]. It is called as ATC code. The code is based on Active ingredients of the medicine. A medicine can have different codes as sometimes it acts on different organs for different indications. Same way, different brands with same active ingredients and same indications can have same ATC code.


Proloid S pharmaceutical companies:

Pharmaceutical companies are drug manufacturing companies that help in complete development of the drug from the background research to formation, clinical trials, release of the drug into the market and marketing of the drug.
Researchers are the persons who are responsible for the scientific research and is responsible for all the background clinical trials that resulted in the development of the drug.


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References

  1. Dailymed."LIOTHYRONINE SODIUM TABLET [PD-RX PHARMACEUTICALS, INC.]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."THYRO-TABS CANINE (LEVOTHYROXINE SODIUM) TABLET [LLOYD, INC. OF IOWA]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. "liothyronine". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Proloid S?

Depending on the reaction of the Proloid S after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Proloid S not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Proloid S addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sdrugs.com conducted a study on Proloid S, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Proloid S consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

Visitor reports

Visitor reported useful

No survey data has been collected yet

Visitor reported side effects

No survey data has been collected yet

Visitor reported price estimates

No survey data has been collected yet

Visitor reported frequency of use

No survey data has been collected yet

Two visitors reported doses

What is the dose of Proloid S drug you are taking?
According to the survey conducted among sdrugs.com website users, the maximum number of people are using the following dose 101-200mg. Few medications come in only one or two doses. Few are specific for adult dose and child dose. The dose of the medicine given to the patient depends on the severity of the symptom/disease. There can be dose adjustments made by the doctor, based on the progression of the disease. Follow-up is important.
Visitors%
101-200mg2
100.0%

Two visitors reported time for results

What is the time duration Proloid S drug must be taken for it to be effective or for it to reduce the symptoms?
Most chronic conditions need at least some time so the dose and the drug action gets adjusted to the body to get the desired effect. The stastistics say sdrugs.com website users needed > 3 month to notice the result from using Proloid S drug. The time needed to show improvement in health condition after using the medicine Proloid S need not be same for all the users. It varies based on other factors.
Visitors%
> 3 month2
100.0%

Visitor reported administration

No survey data has been collected yet

One visitor reported age

Visitors%
30-451
100.0%

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The information was verified by Dr. Rachana Salvi, MD Pharmacology

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