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DRUGS & SUPPLEMENTS
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Levothyroxine Sodium:
Novotiral (Levothyroxine Sodium) for Injection is indicated for the treatment of myxedema coma. Important Limitations of Use: The relative bioavailability between Novotiral (Levothyroxine Sodium) for Injection and oral levothyroxine products has not been established. Caution should be used when switching patients from oral levothyroxine products to Novotiral (Levothyroxine Sodium) for Injection as accurate dosing conversion has not been studied.
Novotiral (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.
An initial intravenous loading dose of Novotiral (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 Novotiral (Levothyroxine Sodium) for Injection.
Novotiral (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 Novotiral (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 Novotiral (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 Novotiral (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.
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.
Reconstitute the lyophilized Novotiral (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 Novotiral (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.
Novotiral (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 )
None.
None.
Excessive bolus dosing of Novotiral (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 Novotiral (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 Novotiral (Levothyroxine Sodium) for Injection is advised.
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 Novotiral 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 Novotiral (Levothyroxine Sodium) for Injection, patients with myxedema coma should also be monitored for previously undiagnosed diabetes insipidus.
Thyroid hormones, including Novotiral (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 .
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.
Many drugs affect thyroid hormone pharmacokinetics and metabolism and may alter the therapeutic response to Novotiral (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 Novotiral (Levothyroxine Sodium) for Injection. ( 7 , 12.3 )
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.
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 Novotiral for Injection dose is increased. Prothrombin time should be closely monitored to permit appropriate and timely dosage adjustments.
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.
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.
Concurrent use may produce marked hypertension and tachycardia; cautious administration to patients receiving thyroid hormone therapy is recommended.
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.
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.
Pregnancy Category A – There are no reported cases of Novotiral (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 Novotiral (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.
Patients in labor who develop myxedema have not been reported in the literature. However, patients should be treated with Novotiral 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.
Adequate replacement doses of thyroid hormones are required to maintain normal lactation. There are no reported cases of Novotiral (Levothyroxine Sodium) for Injection used to treat myxedema coma in patients who are lactating. However, such patients should be treated with Novotiral (Levothyroxine Sodium) for Injection as the risk of nontreatment is associated with a high probability of significant morbidity or mortality to the nursing patient.
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.
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 Novotiral (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 )].
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 Novotiral (Levothyroxine Sodium) for Injection (greater than 500 mcg) are associated with cardiac complications in patients with underlying cardiac disease.
Treatment of Overdosage
Novotiral (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.
Novotiral (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:
Novotiral (Levothyroxine Sodium) for Injection is a sterile, preservative-free lyophilized powder consisting of the active ingredient, Novotiral (Levothyroxine Sodium), and the excipients dibasic sodium phosphate heptahydrate, USP; mannitol, USP; and sodium hydroxide, NF in single-use amber glass vials. Novotiral (Levothyroxine Sodium) for Injection is available at three dosage strengths: 100 mcg per vial, 200 mcg per vial and 500 mcg per vial.
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.
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.
Absorption – Novotiral (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 | 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 | |
Animal studies have not been performed to evaluate the carcinogenic potential, mutagenic potential or effects on fertility of Novotiral for Injection.
No animal toxicology studies have been conducted with Novotiral (Levothyroxine Sodium) for Injection.
No clinical studies have been conducted with Novotiral (Levothyroxine Sodium) for Injection in patients with myxedema coma. However, data from published literature support the intravenous use of Novotiral (Levothyroxine Sodium) for the treatment of myxedema coma.
Novotiral 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 |
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
Novotiral (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
Novotiral (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
Novotiral (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
Novotiral (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
Novotiral (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
Novotiral (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:
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.
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.
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 Novotiral (Liothyronine Sodium) ½ or Novotiral (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:
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.
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.
During postmarketing surveillance, the following events have been observed to have occured in patients administered Novotiral (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.
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.
The dosage of Novotiral (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 Novotiral (Liothyronine Sodium) ½ with increments of one tablet of Novotiral (Liothyronine Sodium) ¼ every 2 to 3 weeks. A lower starting dosage, one tablet of Novotiral (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 Novotiral (Liothyronine Sodium) 1 to one tablet of Novotiral (Liothyronine Sodium) 2 per day. Failure to respond to doses of one tablet of Novotiral (Liothyronine Sodium) 3 suggests lack of compliance or malabsorption. Maintenance dosages of one tablet of Novotiral (Liothyronine Sodium) 1 to one tablet of Novotiral (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 |
Novotiral (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 Novotiral (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.
Depending on the reaction of the Novotiral after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Novotiral 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 Novotiral 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.
Visitors | % | ||
---|---|---|---|
Once in a day | 3 | 75.0% | |
3 times in a day | 1 | 25.0% |
Visitors | % | ||
---|---|---|---|
51-100mg | 2 | 40.0% | |
101-200mg | 1 | 20.0% | |
1-5mg | 1 | 20.0% | |
11-50mg | 1 | 20.0% |
Visitors | % | ||
---|---|---|---|
> 3 month | 2 | 66.7% | |
1 day | 1 | 33.3% |
Visitors | % | ||
---|---|---|---|
Empty stomach | 1 | 50.0% | |
After food | 1 | 50.0% |
Visitors | % | ||
---|---|---|---|
> 60 | 3 | 33.3% | |
46-60 | 3 | 33.3% | |
30-45 | 2 | 22.2% | |
16-29 | 1 | 11.1% |
Hello. Is this the correct medication for Hashimoto Hypotiroidism, because I am just taking Levothyroxine. |
The information was verified by Dr. Rachana Salvi, MD Pharmacology