Action and Spectrum

Actions and Spectrum: 

Actions: 

• Inhibits the production of thyroid hormone by blocking the activity of an enzyme called thyroperoxidase, which is involved in the synthesis of thyroid hormones. 
• Reduces the conversion of the thyroid hormone thyroxine (T4) to its active form, triiodothyronine (T3), by inhibiting another enzyme called 5′-deiodinase. 
• May also have some immunosuppressive effects. 

Spectrum: 

• PTU is mainly used in the treatment of hyperthyroidism, including Graves’ disease, toxic multinodular goiter, and toxic adenoma. 
• It can also be used in the treatment of thyroid storm, a life-threatening complication of hyperthyroidism. 
• PTU may be used in pregnant women with hyperthyroidism, as it is considered safer than methimazole, another medication used for hyperthyroidism, during pregnancy. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Agranulocytosis 

Aplastic anemia 

Hepatitis 

Polyarthritis 

Drowsiness 

Vertigo 

Alopecia 

Erythema nodosum 

Skin ulcers 

Goiter 

Weight gain 

Constipation 

Loss of taste 

Granulopenia 

Leukopenia 

Thrombocytopenia 

Black Box Warning

Black Box Warning: 

Severe liver injury and acute liver failure are rare but serious side effects of propylthiouracil, and patients taking this medication should be closely monitored for symptoms and signs of liver injury. The FDA recommends that healthcare providers measure liver function tests prior to initiating treatment with propylthiouracil and periodically thereafter, especially during the first six months of therapy. 

propylthiouracil should be reserved for those patients who cannot tolerate other treatments, such as methimazole, radioactive iodine, or surgery, due to the potential risk of liver injury. In pregnant women with hyperthyroidism, propylthiouracil may be the treatment of choice during the first trimester of pregnancy due to the strong association of methimazole with congenital malformations during this period. However, in later stages of pregnancy, methimazole is generally preferred due to a lower risk of liver injury in the mother. 

Contraindication / Caution

Contraindication/Caution: 

Contraindications: 

• Known hypersensitivity to PTU or any of its components. 
• Patients with a history of agranulocytosis (a severe blood disorder) or other blood dyscrasias related to PTU use. 

Precautions: 

• Patients with liver disease or a history of liver injury, as PTU can cause severe liver damage. 
• Patients with bone marrow depression or other blood disorders, as PTU can affect blood cell counts. 
• Patients with autoimmune diseases, as PTU may exacerbate these conditions. 
• PTU should be used with caution in pregnant women, particularly during the first trimester, as it can cross the placenta and affect fetal thyroid function. The medication should only be used if the benefits outweigh the risks. 
• PTU can interact with other medications, such as warfarin and digoxin, and patients should be monitored closely for any potential drug interactions. 
• PTU should be used with caution in patients with renal impairment, as it is excreted by the kidneys. 

Pregnancy / Lactation

Pregnancy consideration:  

Category D 

Breastfeeding warnings:  

Propylthiouracil is distributed in breastmilk and hence contraindicated during breastfeeding  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: No evidence shown of risk to the fetus found in animal reproduction studies, and there are not enough studies on pregnant women    
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for a product in humans; Pregnant women must take care of the potential risks. 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms. However, despite potential dangers may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits. The drug is not for pregnant women. 
• Category N: No data is available for the drug under this category. 

Pharmacology

Pharmacology: 

propylthiouracil (PTU) is an antithyroid medication used in the treatment of hyperthyroidism, which is the overactivity of the thyroid gland that leads to excessive thyroid hormone production. Here are some key points about the pharmacology of PTU: 

• Mechanism of action: PTU inhibits the synthesis of thyroid hormones by blocking the iodination of thyroglobulin and the coupling of iodotyrosine residues. It also inhibits the conversion of thyroxine (T4) to triiodothyronine (T3) in peripheral tissues by blocking the enzyme 5′-deiodinase. 
• Pharmacokinetics: PTU is rapidly absorbed after oral administration and reaches peak plasma levels within 30 minutes to 2 hours. The drug is extensively metabolized in the liver and excreted in the urine as metabolites. The half-life of PTU is about 1-2 hours, but the duration of its therapeutic effect is much longer due to the inhibition of thyroid hormone synthesis. 
• Indications: PTU is used to treat hyperthyroidism, including Graves’ disease, toxic multinodular goiter, and thyroid storm. It is also sometimes used in preparation for thyroidectomy or radioactive iodine therapy. 
• Dosage: The usual adult dose of PTU is 100-150 mg three times daily. The dose may be adjusted based on the patient’s response and thyroid function tests. 
• Adverse effects: PTU can cause a variety of side effects, including skin rash, arthralgia, leukopenia, agranulocytosis, hepatotoxicity, and vasculitis. Patients taking PTU should be monitored closely for signs of these adverse effects, especially during the first few months of therapy. 
• Drug interactions: PTU can interact with other medications, such as warfarin, which can increase the risk of bleeding. It can also enhance the effects of other antithyroid drugs, such as methimazole. 

Pharmacodynamics: 

The pharmacodynamics of PTU involve inhibition of both thyroid hormone synthesis and peripheral conversion, leading to a reduction in circulating levels of T4 and T3 and improvement in symptoms of hyperthyroidism. The slow onset and prolonged duration of action of the drug must be considered when managing patients with hyperthyroidism. 

Pharmacokinetics: 

Absorption 

The 75% of drug is absorbed 

Duration of action is 12-24 hours 

The half-life of elimination is 1-2 hours 

Distribution 

The volume of distribution is 0.4 L/kg 

The bound protein is 80-85% 

Peak plasma concentration is achieved in 1-2 hours 

The peak plasma concentration is 6-9 mcg/mL 

Metabolism 

The drug is metabolised in the liver, to glucuronide conjugates, sulfur metabolites, inorganic sulfates 

Elimination and Excretion 

The rate of total body clearance is 7 L/hr 

The drug is excreted 35% in urine

Adminstartion

Administration: 

propylthiouracil (PTU) is an anti-thyroid medication used to treat hyperthyroidism, a condition where the thyroid gland produces too much thyroid hormone. PTU works by inhibiting the production of thyroid hormone by blocking the activity of an enzyme called thyroid peroxidase. 

PTU is usually taken orally in tablet form, and the dose and duration of treatment will depend on the individual patient’s condition and response to the medication. It is important to take the medication exactly as prescribed by the healthcare provider and not to stop taking it abruptly without medical advice, as this can cause a rebound increase in thyroid hormone levels. 

PTU can have several potential side effects, including nausea, vomiting, loss of appetite, headache, dizziness, rash, and joint pain. Rare but serious side effects can also occur, such as liver toxicity and a decrease in white blood cell count. Patients should be monitored closely for any signs of these side effects and advised to seek medical attention immediately if they occur. 

In addition, PTU should not be used during pregnancy unless the benefits outweigh the risks, as it can cross the placenta and potentially harm the developing fetus. It is also important to inform the healthcare provider of any other medications or supplements being taken, as they may interact with PTU and affect its effectiveness or increase the risk of side effects. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: propylthiouracil 

Pronounced: PRO-pil-THYE-oh-URE-a-sil 

Why do we use propylthiouracil? 

propylthiouracil (PTU) is used to treat hyperthyroidism, a condition where the thyroid gland produces too much thyroid hormone. Hyperthyroidism can be caused by various conditions, including Graves’ disease, toxic multinodular goiter, and toxic adenoma. 

PTU works by inhibiting the production of thyroid hormone by blocking the activity of an enzyme called thyroid peroxidase. This enzyme is required for the synthesis of thyroid hormone, and by inhibiting its activity, PTU reduces the amount of thyroid hormone produced by the thyroid gland. 

PTU is often used as a first-line treatment for hyperthyroidism, particularly in patients who cannot tolerate or have contraindications to other anti-thyroid medications like methimazole. PTU may also be used in combination with other medications or radioactive iodine therapy to achieve better control of hyperthyroidism. 

In addition to treating hyperthyroidism, PTU may also be used to prepare patients for thyroid surgery by reducing the size and activity of the thyroid gland before the procedure.