Tirosint

Name: Tirosint

What should I discuss with my healthcare provider before taking Tirosint (levothyroxine)?

Levothyroxine should not be used to treat obesity or weight problems. Dangerous side effects or death can occur from the misuse of levothyroxine, especially if you are taking any other weight-loss medications or appetite suppressants.

Since thyroid hormone occurs naturally in the body, almost anyone can take levothyroxine. However, you may not be able to take this medicine if you have certain medical conditions.

To make sure levothyroxine is safe for you, tell your doctor if you have:

  • a thyroid disorder called thyrotoxicosis;

  • heart disease, coronary artery disease, or a history of blood clots;

  • diabetes (insulin or oral diabetes medication doses may need to be changed when you start taking levothyroxine);

  • anemia (lack of red blood cells);

  • a blood-clotting disorder;

  • osteoporosis, or low bone mineral density;

  • problems with your pituitary gland;

  • any food or drug allergies;

  • an untreated or uncontrolled adrenal gland disorder;

  • if you also take a blood thinner (warfarin, Coumadin, Jantoven); or

  • if you have recently had a heart attack, or are having any symptoms of a heart attack (chest pain or heavy feeling, pain spreading to the jaw or shoulder, nausea, sweating, general ill feeling).

Tell your doctor if you have recently received radiation therapy with iodine (such as I-131).

Levothyroxine is not expected to harm an unborn baby. If you become pregnant while taking levothyroxine, do not stop taking the medicine without your doctor's advice. Having low thyroid hormone levels during pregnancy could harm both mother and baby. Your dose needs may be different during pregnancy.

Levothyroxine can pass into breast milk, but it is not expected to be harmful to a nursing baby. Tell your doctor if you are breast-feeding. Your dose needs may be different while you are nursing.

Do not give this medicine to a child without medical advice. Tirosint is not approved for use by anyone younger than 6 years old.

What are some side effects that I need to call my doctor about right away?

WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:

  • Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
  • Chest pain or pressure or a fast heartbeat.
  • A heartbeat that does not feel normal.
  • Shortness of breath, a big weight gain, or swelling in the arms or legs.
  • Lump on your neck.
  • Headache.
  • Feeling more or less hungry.
  • A change in weight without trying.
  • Loose stools (diarrhea).
  • Stomach cramps.
  • Throwing up.
  • Feeling irritable.
  • Feeling nervous and excitable.
  • Shakiness.
  • Not able to sleep.
  • Bothered by heat.
  • Sweating a lot.
  • Fever.
  • Leg cramps.
  • Muscle weakness.
  • Period (menstrual) changes.

Dosage Forms and Strengths

Tirosint capsules are amber-colored, round/biconvex capsules, imprinted with a dosage strength specific letter on one side and containing a viscous amber-colored liquid and are available as follows:

Strength (mcg) Imprint Code
13 A
25 E
50 G
75 H
88 J
100 K
112 M
125 N
137 P
150 S
175 U
200 Y

Contraindications

Tirosint is contraindicated in patients with uncorrected adrenal insufficiency [see Warnings and Precautions (5.3)].

Drug Interactions

Drugs Known to Affect Thyroid Hormone Pharmacokinetics

Many drugs can exert effects thyroid hormone pharmacokinetics (e.g., absorption, synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to Tirosint (see Tables 2 to 5 below).

Table 2: Drugs That May Decrease T4 Absorption (Hypothyroidism)
Potential impact: Concurrent use may reduce the efficacy of Tirosint by binding and delaying or preventing absorption, potentially resulting in hypothyroidism
Drug or Drug Class Effect
Calcium Carbonate
Ferrous Sulfate
Calcium carbonate may form an insoluble chelate with levothyroxine, and ferrous sulfate likely forms a ferric-thyroxine complex. Administer Tirosint at least 4 hours apart from these agents.
Orlistat Monitor patients treated concomitantly with orlistat and Tirosint for changes in thyroid function.
Bile Acid Sequestrants
-Colesevelam
-Cholestyramine
-Colestipol
Ion Exchange Resins
-Kayexalate
-Sevelamer
Bile acid sequestrants and ion exchange resins are known to decrease levothyroxine absorption. Administer Tirosint at least 4 hours prior to these drugs or monitor thyrotropin (TSH) levels.
Other drugs:
Proton Pump Inhibitors
Sucralfate
Antacids
- Aluminum & Magnesium Hydroxides
- Simethicone
Gastric acidity is an essential requirement for adequate absorption of levothyroxine. Sucralfate, antacids and proton pump inhibitors may cause hypochlorhydria, affect intragastric pH, and reduce levothyroxine absorption. Monitor patients appropriately
Table 3: Drugs That May Alter T4 and Triiodothyronine (T3) Serum Transport Without Affecting Free Thyroxine (FT4) Concentration (Euthyroidism)
Drug or Drug Class Effect
Clofibrate
Estrogen-containing oral contraceptives
Estrogens (oral)
Heroin / Methadone
5-Fluorouracil
Mitotane
Tamoxifen
These drugs may increase serum thyroxine-binding globulin (TBG) concentration.
Androgens / Anabolic Steroids
Asparaginase
Glucocorticoids
Slow-Release Nicotinic Acid
These drugs may decrease serum TBG concentration.
Potential impact (below): Administration of these agents with Tirosint results in an initial transient increase in FT4. Continued administration results in a decrease in serum T4 and normal FT4 and TSH concentrations.
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:
Carbamazepine
Furosemide (> 80 mg IV)
Heparin
Hydantoins
Non-Steroidal Anti-inflammatory Drugs
- Fenamates
These drugs may cause protein-binding site displacement. Furosemide has been shown to inhibit the protein binding of T4 to TBG and albumin, causing an increased free-T4 fraction in serum. Furosemide competes for T4-binding sites on TBG, prealbumin, and albumin, so that a single high dose can acutely lower the total T4 level. 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. Closely monitor thyroid hormone parameters.
Table 4: 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 Tirosint requirements.
Drug or Drug Class Effect
Phenobarbital
Rifampin
Phenobarbital has been shown to reduce the response to thyroxine. Phenobarbital increases L-thyroxine metabolism by inducing uridine 5'-diphospho-glucuronosyltransferase (UGT) and leads to a lower T4 serum levels. Changes in thyroid status may occur if barbiturates are added or withdrawn from patients being treated for hypothyroidism. Rifampin has been shown to accelerate the metabolism of levothyroxine.
Table 5: 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, TSH levels remain normal, and patients are clinically euthyroid. 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 (see Table 3 above).
Other:
Amiodarone
Amiodarone inhibits peripheral conversion of levothyroxine (T4) to triiodothyronine (T3) and may cause isolated biochemical changes (increase in serum free-T4, and decrease or normal free-T3) in clinically euthyroid patients.

Antidiabetic Therapy

Addition of Tirosint therapy in patients with diabetes mellitus may worsen glycemic control and result in increased antidiabetic agent or insulin requirements. Careful monitor glycemic control, especially when thyroid therapy is started, changed, or discontinued [see Warnings and Precautions (5.5)].

Oral Anticoagulants

Tirosint 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 Tirosint dose is increased. Closely monitor coagulation tests to permit appropriate and timely dosage adjustments.

Digitalis Glycosides

Tirosint may reduce the therapeutic effects of digitalis glycosides. Serum digitalis glycoside levels may decrease when a hypothyroid patient becomes euthyroid, necessitating an increase in the dose of digitalis glycosides.

Antidepressant Therapy

Concurrent use of tricyclic (e.g., Amitriptyline) or tetracyclic (e.g., Maprotiline) antidepressants and Tirosint 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 central nervous system stimulation. Tirosint may accelerate the onset of action of tricyclics. Administration of sertraline in patients stabilized on Tirosint may result in increased Tirosint requirements.

Ketamine

Concurrent use of ketamine and Tirosint may produce marked hypertension and tachycardia. Closely monitor blood pressure and heart rate in these patients.

Sympathomimetics

Concurrent use of sympathomimetics and Tirosint 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.

Tyrosine-Kinase Inhibitors

Concurrent use of tyrosine-kinase inhibitors such as imatinib may cause hypothyroidism. Closely monitor TSH levels in such patients.

Drug-Food Interactions

Consumption of certain foods may affect Tirosint absorption thereby necessitating adjustments in dosing [see Dosage and Administration (2.1)]. Soybean flour (infant formula), cottonseed meal, walnuts, and dietary fiber may bind and decrease the absorption of Tirosint from the GI tract. Grapefruit juice may delay the absorption of levothyroxine and reduce its bioavailability.

Drug-Laboratory Test Interactions

Consider changes in TBG concentration when interpreting T4 and T3 values. Measure and evaluate unbound (free) hormone and/or determine the free T4 index (FT4I) in this circumstance. Pregnancy, infectious hepatitis, estrogens, estrogen-containing oral contraceptives, and acute intermittent porphyria increase TBG concentrations. Nephrosis, severe hypoproteinemia, severe liver disease, acromegaly, androgens and corticosteroids decrease TBG concentration. Familial hyper- or hypo-thyroxine binding globulinemias have been described, with the incidence of TBG deficiency approximating 1 in 9000.

PRINCIPAL DISPLAY PANEL - 50 mcg Capsule Blister Pack Carton

Tirosint®
(levothyroxine sodium) capsules

NDC 24090-492-84

50 mcg
per capsule

Rx Only

Do not remove individual capsules from blister packaging until ready to use

AKRIMAX
PHARMACEUTICALS

4 blisters x 7 capsules

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