Side Effects of Propylthiouracil (PTU)

Propylthiouracil (PTU) is an anti-thyroid drug used to manage hyperthyroidism which is due to an overactive thyroid gland.

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 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. 

Common side effects of propylthiouracil (PTU) include

• skin effects (such as rash, itching, hives, abnormal hair loss, and skin pigmentation),
• swelling,
• nausea,
• vomiting,
• heartburn,
• loss of taste,
• joint or muscle aches,
• numbness, and
• headache.

Serious side effects of propylthiouracil (PTU) include

• decreased white blood cells (agranulocytosis) (symptoms include infectious lesions of the throat, the gastrointestinal tract, and skin with an overall feeling of illness and fever),
• decreased blood platelets (thrombocytopenia) which can lead to excessive bleeding, and
• severe liver injury and acute liver failure, which can be fatal.

Drug interactions of propylthiouracil (PTU) include oral blood thinners, because PTU may increase their effects.

Hyperthyroidism may cause increased elimination of beta-blockers. 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 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 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 toxicity of theophylline.

PTU crosses the placenta and may harm a 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. Consult your doctor before breastfeeding.

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.

Major adverse reactions (much less common than the minor adverse reactions) include

• inhibition of myelopoiesis (agranulocytosis, granulopenia, and thrombo-cytopenia),
• aplastic anemia,
• drug fever, a lupus-like syndrome including solenomegaly,
• hepatitis,
• periartentis, and
• hypoprothrombinemia and bleeding.

There were also reports of the following:

• nephritis,
• glomerulonephritis,
• interstitial pneumonitis,
• exfoliative dermatitis, and
• erythema nodosum.

Reports of a vasculitic syndrome associated with the presence of anti-neutrophilic cytoplasmic antibodies (ANCA) have also been received.

Manifestations of ANCA-positive vasculitis may include rapidly progressive glomerulonephritis (crescentic and pauci-immune necrotizing glomerulonephritis) sometimes leading to

• acute renal failure;
• fever;
• pulmonary infiltrates or alveolar hemorrhage;
• skin ulcers; and
• leucocytoclastic vasculitis.

Minor adverse reactions include

• skin rash,
• urticaria,
• nausea,
• vomiting,
• epigastric distress,
• arthralgia,
• paresthesias,
• loss of taste,
• abnormal Ioss of hair,
• myalgia,
• headache,
• pruritus,
• drowsiness,
• neuritis,
• edema,
• vertigo,
• skin pigmentation,
• jaundice,
• sialadenopathy,
• lymphadenopathy,
• vasculitis,
• glomerulonephritis, and
• taste perversion.

It should be noted that about 10% of patients with untreated hyperthyroidism have leukopenia (white blood cell count of less than 4,000/mm³), often with relative granulopenia.

Anticoagulants (oral)

The activity of anticoagulants may be potentiated by anti-vitamin-K activity attributed to propylthiouracil (propylthiouracil (propylthiouracil (propylthiouracil tablet) tablet) tablet) .

β-Adrenergic blocking agents

Hyperthyroidism may cause an increased clearance of beta blockers with a high extraction ratio. A dose reduction 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 required.

Theophylline

Theophylline clearance may decrease when hyperthyroid patients on a stable theophylline regimen become euthyroid; a reduced dose of theophylline may be needed.