Propylthiouracil 50 MG Oral Tablet
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.
There are cases of liver injury, including liver faillure 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.
The use of an alternative antithyroid medication (e.g., methimazole) may be advisable following the first trimester of pregnancy (see PRECAUTIONS, Pregnancy ).
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, propylthouracil should be discontinued immediately and liver function tests and ALT and AST levels obtained.
Agranulocytosis Agranulocytosis occurs in approximately 0.2% to 0.5% of patients and is a potentially llife-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), ANCA-positive vasculitis, hepatitis, interstitial pneumonitis, fever, or exfoliative dermatitis is suspected, and the patient’s bone marrow indices should be obtained.
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 ).
DRUG INTERACTIONS
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 dosage 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.
Carcinogenesis, Mutagenesis, Impairment of Fertility Laboratory animals treated with propylthiouracil for > 1 year have demonstrated thyroid hyperplasia and carcinoma formation 1 .
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.
Pregnancy Pregnancy Category D.
SEE WARNINGS .
Nursing Mothers Propylthiouracil is transferred to breasdt milk to a small extent and therefore likely results in clinically insignificant doses to the suckling infant.
One one study, nine lactating women were administered 400 mg of propylthiouracil by mouth.
The mean amount of propylthiouracil excreted during 4 hours after drug administration was 0.025% of the administered dose.
Pediatric Use Post-marketing reports of severe liver injury including hepatic failure requiring liver transplantation or resulting in death have been reported in the pediatric population.
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
: 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 patient’s medical status.
DESCRIPTION
: Propylthiouracil (6-propyl-2-thiouracil) is one of the thiocarbamide compounds.
It is a white, 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 50 mg and the following inactive ingredients: anhydrous lactose, magnesium stearate, microcrystalline cellulose, pregelatinized starch, and sodium starch glycolate.
Structural Formula
HOW SUPPLIED
: Propylthiouracil Tablets, USP, 50 mg: White, Round, Scored Tablet, Debossed “West-ward 480”.
• Bottles of 100 tablets.
• Bottles of 1000 tablets.
• Unit Dose Boxes of 100 tablets.
Store at 20-25°C (68-77°F) [See USP Controlled Room Temperature].
Protect from light and moisture.
Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
Reference: 1.
International Agency for Research on Cancer, IARC Monographs on the Evaluation of the Carcinogenic Risk of Chemicals to Man.
1974; 7:67-76.
Manufactured By: West-ward Pharmaceutical Corp.
Eatontown, NJ 07724 Revised August 2011
INDICATIONS AND USAGE
: Propylthiouracil is indicated: • in patients with Graves’ 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.
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 can not tolerate methimazole and in whom radioactive iodine therapy or surgery are not appropriate treatments for the management of hyperthyroidism.
Because of the risk of fetal abnormalities associated with methimazole, proplythiouracil 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 ).
INFORMATION FOR PATIENTS
Information for Patients Patients should be advised that if they become pregnant or intend to become pregnant white taking an antithyroid drug, they should contact their physician immediately about their therapy.
Patients should report immediately any evidence of illness, particularly sore throat, skin eruptions, fever, headache, or general malaise.
They also should report symptoms suggestive of hepatic dysfunction (anorexia, pruritis, right upper quadrant pain, etc).
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.
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.
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 reported with doses as low as 50 mg/day, most cases were associated with doses of 300 mg/day and higher.
Geriatric Use Clinical studies of propylthiouracil did not include sufficient numbers of subjects aged 65 and 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.