Propylthiouracil (PTU)

Propylthiouracil (PTU) is an oral medication that is used to manage hyperthyroidism which is due to an overactive thyroid gland.

It is an anti-thyroid drug that has a mechanism of action that is similar to methimazole (Tapazole). Graves' disease is the most common cause of hyperthyroidism. It is an autoimmune disease where an individual makes antibodies to thyroid stimulating hormone receptors on cells of the thyroid gland and then trigger the overproduction of thyroid hormone by the cells.

The two thyroid hormones manufactured by the thyroid gland, thyroxine (T4 ) and triiodothyronine (T3), are formed by combining iodine and a protein called thyroglobulin with the assistance of an enzyme called peroxidase. PTU inhibits iodine and peroxidase from their normal interactions with thyroglobulin to form T4 and T3. This action decreases production of thyroid hormone. PTU also interferes with the conversion of T4 to T3, and, since T3 is more potent than T4, this also reduces the activity of thyroid hormones. The FDA approved PTU in July 1947.

The most common side effects are related to the skin, such as:

• rash,
• itching,
• hives,
• abnormal
• hair loss, and
• skin pigmentation.

Other important side effects include:

• swelling,
• nausea,
• vomiting,
• heartburn,
• loss of taste,
• joint or muscle aches,
• numbness, and
• headache.

Less common but serious side effects have occurred with PTU therapy. A decrease of white blood cells in the blood (agranulocytosis) may occur. Symptoms and signs of agranulocytosis include infectious lesions of the throat, the gastrointestinal tract, and skin with an overall feeling of illness and fever.

A decrease in blood platelets (thrombocytopenia) also may occur. Since platelets are important for the clotting of blood, thrombocytopenia may lead to excessive bleeding. Severe liver injury and acute liver failure, in some cases fatal, have been associated with PTU. Some adults and pediatric patients required liver transplantation.

• The initial adult dose of PTU is 300 mg/day divided into 3 divided doses. PTU is usually administered every eight hours.
• Patients with large goiters may require initial doses of up to 900 mg daily.
• The usual long-term adult dose after initial treatment is 100-150 mg/day.

• PTU may increase the effect of oral blood thinners, for example warfarin. Therefore, warfarin dose changes and monitoring for the effects of warfarin on blood clotting are necessary.
• Hyperthyroidism may cause increased elimination of beta blockers (for example, propranolol [Inderal, Inderal LA, Innopran XL)). Once hyperthyroidism is reversed the excretion of beta-blockers may return to normal and less beta-blocker will be needed to provide the same effect.
• Digoxin (Lanoxin) blood levels may be increased when hyperthyroidism is reversed in patients on a stable digoxin dose. A smaller dose of digoxin may be needed in order to avoid the toxicity of digoxin. Similarly, theophylline elimination may decrease when hyperthyroidism is reversed in patients on a stable theophylline dose. A reduced dose of theophylline may be needed in order to avoid the toxicity of theophylline.

• PTU crosses the placenta and may cause harm to the fetus. If it is necessary to use PTU during pregnancy the lowest effective dose should be used. Since methimazole is associated with fetal abnormalities, PTU is used during the first trimester if an antithyroid drug is needed.
• PTU is excreted in breast milk in small amounts.

What preparations of propylthiouracil are available?

• Tablet: 50 mg.

How should I keep propylthiouracil stored?

• PTU should be stored at room temperature, 15 C - 30 C (59 F - 86 F).