DRUG STUDY

PROPYLTHIOURACIL

Class: Antithyroid agent

Trade Names: Propylthiouracil Tablets 50 mg

Pharmacology: Inhibits synthesis of thyroid hormones.

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 300mg/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 86F.

Drug Interactions
Anticoagulants, oral (eg, warfarin)
The activity of anticoagulants may be potentiated by antivitamin 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.

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.

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.

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.