Product Elements:
Propylthiouracil propylthiouracil propylthiouracil propylthiouracil lactose monohydrate starch, corn silicon dioxide povidone magnesium stearate 348
Drug Interactions:
â drug interactions anticoagulants (oral): due to the potential inhibition of vitamin k activity by propylthiouracil, the activity of oral anticoagulants (e.g., warfarin) may be increased; additional monitoring of pt/inr should be considered, especially before surgical procedures. beta-adrenergic blocking agents: hyperthyroidism may cause an increased clearance of beta blockers with a high extraction ratio. a reduced dose of beta-adrenergic blockers may be needed when a hyperthyroid patient becomes euthyroid. digitalis glycosides: serum digitalis levels may be increased when hyperthyroid patients on a stable digitalis glycoside regimen become euthyroid; a reduced dose of digitalis glycosides may be needed. theophylline: theophylline clearance may decrease when hyperthyroid patients on a stable theophylline regimen become euthyroid; a reduced dose of theophylline may be needed.
Boxed Warning:
Warning severe liver injury and acute liver failure, in some cases fatal, have been reported in patients treated with propylthiouracil. these reports of hepatic reactions include cases requiring liver transplantation in adult and pediatric patients. propylthiouracil should be reserved for patients who cannot tolerate methimazole and in whom radioactive iodine therapy or surgery are not appropriate treatments for the management of hyperthyroidism. propylthiouracil may be the treatment of choice when an antithyroid drug is indicated during or just prior to the first trimester of pregnancy (see warnings and precautions ).
Indications and Usage:
Indications and usage propylthiouracil tablets are indicated: in patients with gravesâ disease with hyperthyroidism or toxic multinodular goiter who are intolerant of methimazole and for whom surgery or radioactive iodine therapy is not an appropriate treatment option to ameliorate symptoms of hyperthyroidism in preparation for thyroidectomy or radioactive iodine therapy in patients who are intolerant of methimazole
Warnings:
Warnings liver toxicity liver injury resulting in liver failure, liver transplantation, or death, has been reported with propylthiouracil therapy in adult and pediatric patients. no cases of liver failure have been reported with the use of methimazole in pediatric patients. for this reason, propylthiouracil is not recommended for pediatric patients except when methimazole is not well-tolerated and surgery or radioactive iodine therapy are not appropriate therapies. biochemical monitoring of liver function (bilirubin, alkaline phosphatase) and hepatocellular integrity (alt, ast) is not expected to attenuate the risk of severe liver injury due to its rapid and unpredictable onset. patients should be informed of the risk of liver failure. patients should be instructed to report any symptoms of hepatic dysfunction (anorexia, pruritus, right upper quadrant pain, etc.), particularly in the first six months of therapy. when these symptoms occur, propylthiouracil should be discontinued immedia
Read more...tely and liver function tests and alt and ast levels obtained. use in pregnancy there are cases of liver injury, including liver failure and death, in women treated with propylthiouracil during pregnancy. two reports of in utero exposure with liver failure and death of a newborn have been reported. if propylthiouracil is used during pregnancy, or if the patient becomes pregnant while taking propylthiouracil, the patient should be warned of the rare potential hazard to the mother and fetus of liver damage. propylthiouracil crosses the placenta and can cause fetal goiter and cretinism when administered to a pregnant woman (see precautions , pregnancy ). after the first trimester of pregnancy, the use of an alternative antithyroid medication may be advisable (see precautions , pregnancy ). agranulocytosis agranulocytosis occurs in approximately 0.2% to 0.5% of patients and is a potentially life-threatening side effect of propylthiouracil therapy. agranulocytosis typically occurs within the first 3 months of therapy. patients should be instructed to immediately report any symptoms suggestive of agranulocytosis, such as fever or sore throat. leukopenia, thrombocytopenia, and aplastic anemia (pancytopenia) may also occur. propylthiouracil should be discontinued if agranulocytosis, aplastic anemia (pancytopenia) is suspected, and the patient's bone marrow indices should be obtained. vasculitis cases of vasculitis resulting in severe complications and death have been reported in patients receiving propylthiouracil therapy. the cases of vasculitis include: glomerulonephritis, leukocytoclastic cutaneous vasculitis, alveolar/pulmonary hemorrhage, cerebral angiitis, and ischemic colitis. most cases were associated with anti-neutrophilic cytoplasmic antibodies (anca)-positive vasculitis. in some cases, vasculitis resolved/improved with drug discontinuation; however, more severe cases required treatment with additional measures including corticosteroids, immunosuppressant therapy, and plasmapheresis. if vasculitis is suspected, discontinue therapy and initiate appropriate intervention. hypothyroidism propylthiouracil can cause hypothyroidism necessitating routine monitoring of tsh and free t4 levels with adjustments in dosing to maintain a euthyroid state. because the drug readily crosses placental membranes, propylthiouracil can cause fetal goiter and cretinism when administered to a pregnant woman (see precautions, pregnancy ).
General Precautions:
General patients should be instructed to report any symptoms of hepatic dysfunction (anorexia, pruritus, jaundice, light colored stools, dark urine, right upper quadrant pain, etc.), particularly in the first six months of therapy. when these symptoms occur, measurement should be made of liver function (bilirubin, alkaline phosphatase) and hepatocellular integrity (alt/ast levels). patients who receive propylthiouracil should be under close surveillance and should be counseled regarding the necessity of immediately reporting any evidence of illness, particularly sore throat, skin eruptions, fever, headache, or general malaise. in such cases, white blood cell and differential counts should be obtained to determine whether agranulocytosis has developed. particular care should be exercised with patients who are receiving concomitant drugs known to be associated with agranulocytosis.
Dosage and Administration:
Dosage and administration propylthiouracil is administered orally. the total daily dosage is usually given in 3 equal doses at approximately 8-hour intervals. adults the initial dose is 300 mg daily. in patients with severe hyperthyroidism, very large goiters, or both, the initial dose may be increased to 400 mg daily; an occasional patient will require 600 to 900 mg daily initially. the usual maintenance dose is 100 to 150 mg daily. pediatric patients propylthiouracil is generally not recommended for use in the pediatric patient population except in rare instances in which other alternative therapies are not appropriate options. studies evaluating appropriate dosing regimen have not been conducted in the pediatric population although general practice would suggest initiation of therapy in patients 6 years or older at a dosage of 50 mg daily with careful upward titration based on clinical response and evaluation of tsh and free t4 levels. although cases of severe liver injury have been
Read more... reported with doses as low as 50 mg/day, most cases were associated with doses of 300 mg/day and higher. geriatric patients clinical studies of propylthiouracil did not include sufficient numbers of subjects aged 65 or over to determine whether they respond differently from younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, dose selection for an elderly patient should be cautious reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
Contraindications:
Contraindications propylthiouracil is contraindicated in patients who have demonstrated hypersensitivity to the drug or any of the other product components.
Adverse Reactions:
Adverse reactions the following adverse reactions have been reported with the use of propylthiouracil. because these events generally come from voluntary reporting from a population of uncertain size, it is not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. severe adverse reactions include liver injury presenting as hepatitis, liver failure necessitating liver transplantation or resulting in death (see warnings ). inhibition of myelopoiesis (agranulocytosis, granulopenia, aplastic anemia, and thrombocytopenia), drug fever, a lupus-like syndrome (including splenomegaly and vasculitis), periarteritis, hypoprothrombinemia, and bleeding have been reported. nephritis, glomerulonephritis, interstitial pneumonitis, exfoliative dermatitis, and erythema nodosum have also been reported. there are reports of a vasculitis associated with the presence of anti-neutrophilic cytoplasmic antibodies (anca), resulting in severe complications and death (
Read more...see warnings ). there have been rare reports of serious hypersensitivity reactions (e.g., stevens johnson syndrome and toxic epidermal necrolysis) in patients treated with propylthiouracil. other adverse reactions include skin rash, uticaria, nausea, vomiting, epigastric distress, arthralgia, paresthesias, loss of taste, taste perversion, abnormal loss of hair, myalgia, headache, pruritus, drowsiness, neuritis, edema, vertigo, skin pigmentation, jaundice, sialadenopathy, and lymphadenopathy. to report suspected adverse events, contact teva at 1-888-838-2872 or fda at 1-800-fda-1088 or http://www.fda.gov/medwatch for voluntary reporting of adverse reactions.
Drug Interactions:
â drug interactions anticoagulants (oral): due to the potential inhibition of vitamin k activity by propylthiouracil, the activity of oral anticoagulants (e.g., warfarin) may be increased; additional monitoring of pt/inr should be considered, especially before surgical procedures. beta-adrenergic blocking agents: hyperthyroidism may cause an increased clearance of beta blockers with a high extraction ratio. a reduced dose of beta-adrenergic blockers may be needed when a hyperthyroid patient becomes euthyroid. digitalis glycosides: serum digitalis levels may be increased when hyperthyroid patients on a stable digitalis glycoside regimen become euthyroid; a reduced dose of digitalis glycosides may be needed. theophylline: theophylline clearance may decrease when hyperthyroid patients on a stable theophylline regimen become euthyroid; a reduced dose of theophylline may be needed.
Use in Pregnancy:
Pregnancy see warnings . in pregnant women with untreated or inadequately treated gravesâ disease, there is an increased risk of adverse events of maternal heart failure, spontaneous abortion, preterm birth, stillbirth and fetal or neonatal hyperthyroidism. if propylthiouracil is used during pregnancy, or if the patient becomes pregnant while taking propylthiouracil, the patient should be warned of the rare potential hazard to the mother and fetus of liver damage. because propylthiouracil crosses placental membranes and can induce goiter and cretinism in the developing fetus, it is important that a sufficient, but not excessive, dose be given during pregnancy. in many pregnant women, the thyroid dysfunction diminishes as the pregnancy proceeds; consequently a reduction of dosage may be possible. in some instances, antithyroid therapy can be discontinued several weeks or months prior to delivery. since methimazole may be associated with the rare development of fetal abnormalities p
Read more...ropylthiouracil may be the preferred agent during the first trimester of pregnancy. given the potential for maternal hepatotoxicity from propylthiouracil, it may be preferable to switch from propylthiouracil to methimazole for the second and third trimesters during pregnancy.
Pediatric Use:
Pediatric use postmarketing reports of severe liver injury including hepatic failure requiring liver transplantation or resulting in death have been reported in the pediatric population (see warnings ). no such reports have been observed with methimazole. as such, propylthiouracil is not recommended for use in the pediatric population except in rare instances in which methimazole is not well-tolerated and surgery or radioactive iodine therapy are not appropriate. when used in children, parents and patients should be informed of the risk of liver failure. if patients taking propylthiouracil develop tiredness, nausea, anorexia, fever, pharyngitis, or malaise, propylthiouracil should be discontinued immediately by the patient, a physician should be contacted, and a white blood cell count, liver function tests, and transaminase levels obtained.
Overdosage:
Overdosage signs and symptoms nausea, vomiting, epigastric distress, headache, fever, arthralgia, pruritus, edema, and pancytopenia. agranulocytosis is the most serious effect. rarely, exfoliative dermatitis, hepatitis, neuropathies or cns stimulation or depression may occur. no information is available on the following: ld 50 ; concentration of propylthiouracil in biologic fluids associated with toxicity and/or death; the amount of drug in a single dose usually associated with symptoms of overdosage; or the amount of propylthiouracil in a single dose likely to be life-threatening. treatment 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 patientâs medical status.
Description:
Description propylthiouracil, usp is one of the thiocarbamide compounds. it is a white, powdery, crystalline substance that has a bitter taste and is very slightly soluble in water. propylthiouracil is an antithyroid drug administered orally. the structural formula is: each tablet contains propylthiouracil, usp 50 mg and the following inactive ingredients: colloidal silicon dioxide, corn starch, lactose monohydrate, magnesium stearate, povidone, and pregelatinized corn starch,. 1
Clinical Pharmacology:
Clinical pharmacology propylthiouracil inhibits the synthesis of thyroid hormones and thus is effective in the treatment of hyperthyroidism. the drug does not inactivate existing thyroxine and triiodothyronine that are stored in the thyroid or circulating in the blood, nor does it interfere with the effectiveness of thyroid hormones given by mouth or by injection. propylthiouracil inhibits the conversion of thyroxine to triiodothyronine in peripheral tissues and may therefore be an effective treatment for thyroid storm. propylthiouracil is readily absorbed and is extensively metabolized. approximately 35% of the drug is excreted in the urine, in intact and conjugated forms, within 24 hours.
Carcinogenesis and Mutagenesis and Impairment of Fertility:
Carcinogenesis, mutagenesis, impairment of fertility laboratory animals treated with propylthiouracil for greater than 1 year have demonstrated thyroid hyperplasia and carcinoma formation. such animal findings are seen with continuous suppression of thyroid function by sufficient doses of a variety of antithyroid agents, as well as in dietary iodine deficiency, subtotal thyroidectomy, and implantation of autonomous thyrotropic hormone-secreting pituitary tumors. pituitary adenomas have also been described.
How Supplied:
How supplied propylthiouracil tablets, usp are available as follows: 50 mg â each white, round, tablet imprinted with on one side and 348 and partial bisect on the other side contains 50 mg of propylthiouracil, usp. tablets are supplied in bottles of 100 (ndc 0228-2348-10). dispense in a well-closed container as defined in the usp. store at 25°c (77°f); excursions permitted to 15° to 30°c (59° to 86°f) [see usp controlled room temperature]. c66868e0-figure-02
Information for Patients:
Information for patients patients should be advised that if they become pregnant or intend to become pregnant while taking an antithyroid drug, they should contact their physician immediately about their therapy. patients should report immediately any evidence of illness, in particular sore throat, skin eruptions, fever, headache, or general malaise. they also should report symptoms suggestive of hepatic dysfunction (anorexia, pruritus, right upper quadrant pain, etc.). inform patients that cases of vasculitis resulting in severe complications and death have occurred with propylthiouracil. inform patients to promptly report symptoms that may be associated with vasculitis including new rash, hematuria or decreased urine output, dyspnea or hemoptysis (see warnings and adverse reactions ).
Package Label Principal Display Panel:
Package label.principal display panel ndc 0228-2348-10 propylthiouracil tablets, usp 50 mg pharmacist: dispense the accompanying medication guide to each patient. rx only 100 tablets 1