Procarbizole

Uses

Procarbizole is used for:

• 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

Procarbizole is also used to associated treatment for these conditions: Hyperthyroidism, Thyrotoxic crisis, Severe alcoholic liver disease

How Procarbizole works

Procarbizole binds to thyroid peroxidase and thereby inhibits the conversion of iodide to iodine. Thyroid peroxidase normally converts iodide to iodine (via hydrogen peroxide as a cofactor) and also catalyzes the incorporation of the resulting iodide molecule onto both the 3 and/or 5 positions of the phenol rings of tyrosines found in thyroglobulin. Thyroglobulin is degraded to produce thyroxine (T4) and tri-iodothyronine (T3), which are the main hormones produced by the thyroid gland. Therefore propylthiouracil effectively inhibits the production of new thyroid hormones.

Dosage

Procarbizole dosage

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: Procarbizole 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.

Side Effects

The most common side effects of Procarbizole include:

• nausea
• muscle pain
• vomiting
• headache
• upper stomach pain or tenderness
• sleepiness
• joint pain
• nerve pain
• itching or tingling
• swelling (edema)
• loss or change in taste
• dizziness
• loss of hair
• enlarged salivary glands or enlarged lymph node

Toxicity

Oral, rat: LD₅₀ = 1250 mg/kg.

Precaution

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.

Interaction

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.

Food Interaction

• Take at the same time every day.

Procarbizole Drug Interaction

Moderate: metoprolol, metoprolol, levothyroxineUnknown: aspirin, aspirin, lorazepam, loratadine, omega-3 polyunsaturated fatty acids, furosemide, escitalopram, acetaminophen, montelukast, acetaminophen, valproic acid, thiamine, cyanocobalamin, pyridoxine, ascorbic acid, cholecalciferol, alprazolam

Procarbizole Disease Interaction

Major: blood dyscrasias, hepatotoxicity, hypoprothombinemiaModerate: hypothyroidism

Elimination Route

Well absorbed following oral administration.

Half Life

2 hours

Elimination Route

Procarbizole 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.

Pregnancy & Breastfeeding use

Pregnancy Category D. 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. Procarbizole crosses the placenta and can cause fetal goiter and cretinism when administered to a pregnant woman. After the first trimester of pregnancy, the use of an alternative antithyroid medication may be advisable.

Nursing Mothers: Procarbizole is present in breast milk to a small extent and therefore likely results in clinically insignificant doses to the nursing infant. In 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.

Contraindication

Procarbizole is contraindicated in patients who have demonstrated hypersensitivity to the drug or any of the other product components.

Acute Overdose

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.

Storage Condition

Store at controlled room temperature 15°-30°C

Innovators Monograph

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