Propylthiouracil

Pronunciation

Pronunciation: PROE-pil-THYE-oh-URE-a-sil
Class: Antithyroid agent

Trade Names

Propylthiouracil
- Tablets 50 mg

Propyl-Thyracil (Canada)

Pharmacology

Inhibits synthesis of thyroid hormones.

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Pharmacokinetics

Absorption

Readily absorbed from the GI tract.

Metabolism

Extensively metabolized.

Elimination

Urine (35%).

Indications and Usage

For treatment of 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 regimen; to ameliorate hyperthyroidism in preparation for subtotal thyroidectomy or radioactive iodine therapy in patients who are intolerant of methimazole.

Unlabeled Uses

Management of alcoholic liver disease.

Contraindications

Hypersensitivity to propylthiouracil or any of the product's components.

Dosage and Administration

Adults

PO 300 mg/day in 3 equal doses every 8 h initially. In patients with severe hyperthyroidism or very large goiters, initial dosage may be increased to 400 mg/day, occasionally up to 600 to 900 mg/day. The maintenance dosage is 100 to 150 mg/day in divided doses every 8 h.

Children 6 y of age and older

PO Propylthiouracil is generally not recommended for use in children, except in rare instances in which other alternative therapies are not appropriate options. The initial dosage is 50 mg/day in divided doses every 8 h. Carefully titrate upward based on clinical response and evaluation of TSH and free T4 levels.

General Advice

Give with meals to minimize GI irritation.

Storage/Stability

Store at 59° to 86°F.

Drug Interactions

Anticoagulants, oral (eg, warfarin)

The activity of anticoagulants may be potentiated by anti–vitamin K activity attributed to propylthiouracil. Monitor PT/INR and adjust the warfarin dose as needed.

Beta-blockers (eg, propranolol)

Increased effects of beta-blockers. A dose reduction of beta-blockers may be needed when a hyperthyroid patient becomes euthyroid.

Corticosteroids (eg, prednisolone)

Propylthiouracil may decrease pharmacologic effects and plasma concentrations of corticosteroids. Larger corticosteroids doses may be needed during coadministration of propylthiouracil.

Digitalis glycosides (eg, digoxin)

Increased digitalis levels, resulting in toxicity. A dose reduction of digitalis glycoside may be needed when a hyperthyroid patient becomes euthyroid.

Theophylline

Altered theophylline Cl in hyperthyroid or hypothyroid patients. A dose reduction of theophylline may be needed when a hyperthyroid patient becomes euthyroid.

Adverse Reactions

CNS

Drowsiness, headache, neuritis, paresthesia, vertigo.

Dermatologic

Abnormal hair loss, erythema nodosum, exfoliative dermatitis, lupus-like syndrome (splenomegaly, vasculitis), pruritus, rash, skin pigmentation, skin rash, skin ulcers, urticaria.

EENT

GI

Epigastric distress, loss of taste, nausea, taste perversion, vomiting.

Genitourinary

Glomerulonephritis, nephritis.

Hepatic

Hepatitis; jaundice; liver failure; liver injury resulting in hepatitis; a need for transplantation.

Hematologic

Aplastic anemia, hypoprothrombinemia and bleeding, myelopoiesis (eg, agranulocytosis, granulopenia, thrombocytopenia).

Musculoskeletal

Arthralgia, myalgia.

Respiratory

Alveolar hemorrhage, interstitial pneumonitis, pulmonary infiltrates.

Miscellaneous

Antineutrophil cytoplasmic antibody (ANCA)–positive vasculitis syndrome, including rapidly progressive glomerulonephritis sometimes leading to acute renal failure; drug fever; edema; leukocytoclastic vasculitis; lymphadenopathy; periarteritis; sialadenopathy.

Precautions

Warnings

Hepatotoxicity

Severe liver injury and acute liver failure, sometimes fatal or requiring liver transplantation, have been reported. Reserve for patients who are intolerant to methimazole and are not candidates for radioactive iodine or surgery.

Pregnancy

Because of the risks of fetal abnormalities associated with methimazole, propylthiouracil may be the treatment of choice when an antithyroid agent is indicated during or just prior to the first trimester.


Monitor

Periodically monitor thyroid function tests and prothrombin time during therapy. Measure alkaline phosphatase, ALT, AST, and bilirubin if symptoms of hepatic dysfunction occur. Measure CBC with differential if symptoms of infection develop.


Pregnancy

Category D . Cases of liver injury, including liver failure and death, have been reported in pregnant women using propylthiouracil. Other agents (eg, methimazole) may be preferred following the first trimester of pregnancy.

Lactation

Excreted.

Children

Severe liver injury, including hepatic failure requiring liver transplantation or resulting in death, has been reported in children. Propylthiouracil is not recommended for use in children except in rare instances in which methimazole is not well-tolerated and surgery or radioactive iodine therapy is not appropriate.

Hematologic effects

Agranulocytosis, a potentially life-threatening adverse reaction, may occur. Leukopenia, thrombocytopenia, and aplastic anemia may also occur.

Hemorrhagic effects

May cause hypoprothrombinemia and bleeding.

Hypothyroidism

May occur.

Overdosage

Symptoms

Agranulocytosis; arthralgia; CNS depression or stimulation; edema; epigastric distress; exfoliative dermatitis; fever; headache; hepatitis; nausea; neuropathy; pancytopenia; pruritus; vomiting.

Patient Information

  • Instruct patient to take resting pulse daily and encourage patient to keep recorded chart.
  • Advise patient to monitor weight at least 2 to 3 times/wk or per health care provider instruction, obtaining weight at same time, using same scale. Encourage patient to keep recorded chart.
  • Emphasize importance of following dietary restrictions regarding shellfish, iodized salt, and other foods high in iodine.
  • Explain that desired response may take several months if the thyroid is greatly enlarged.
  • Advise patient to carry medical identification (eg, card, bracelet) at all times describing medications.
  • Instruct patient to notify dentist or health care provider of drug regimen before surgical or dental procedures.
  • Emphasize importance of follow-up visits to monitor effectiveness of drug therapy.
  • Caution patient not to stop taking medication abruptly to avoid thyroid crisis.
  • Instruct patient to report the following symptoms to health care provider: sore throat, fever, rash, mouth sores; cold intolerance, mental depression; tachycardia, irritability; persistent nausea, steatorrhea, or vomiting; drowsiness; yellowing of skin or whites of eyes; unusual bleeding or bruising.
  • Advise patient that drug may cause drowsiness and to use caution while driving or performing other activities requiring mental alertness.

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