Propylthiouracil

Propylthiouracil (PTU) is a thiourea derivative and belongs to the group of thyreostatics, which are used for the symptomatic treatment of pathological hyperthyroidism (hyperthyroidism).

Propylthiouracil has a thyrostatic effect by binding to thyroid peroxidase and thus preventing the conversion of iodide to iodine. Thyroid peroxidase normally converts iodide to iodine (via hydrogen peroxide as a cofactor) and catalyzes the incorporation of the resulting iodide molecule into both the 3- and 5-positions of the phenol rings of tyrosines found in thyroglobulin. Thyroglobulin is finally degraded to thyroxine (T4) and triiodothyronine (T3), which are the most important hormones of the thyroid gland.

Propylthiouracil is rapidly and almost completely absorbed from the intestine.

After a single oral dose, the maximum serum concentration is reached within one to two hours, with biologically relevant levels being measured after 20 to 30 minutes. In contrast to thiamazole, propylthiouracil is strongly bound to plasma proteins (80-85%). The bioavailability of propylthiouracil is 53 to 88% and the half-life is about one hour. Similar to thiamazole, propylthiouracil is eliminated both renally and with bile. Excretion with feces is low, indicating an enterohepatic circulation. Both propylthiouracil and thiamazole are able to cross the human placenta.

See Embryotox

As a rule, propylthiouracil is administered every 6 to 8 hours.

Adults, adolescents and children over 10 years of age:

The starting dose for mild clinical activity of hyperthyroidism is 100 to 300 mg propylthiouracil per day, corresponding to 2 to 3 single doses of 50 to 100 mg each (1 to 2 tablets). In severe cases and after iodine contamination, higher initial doses of 300 mg to 600 mg propylthiouracil (6 to 12 tablets) per day are recommended, divided into 4 to 6 single doses. The maintenance dose is 50 to 150 mg propylthiouracil (1 to 3 tablets) per day.

Children between 6 and 10 years of age:

The starting dose is 50 - 150 mg propylthiouracil (1 to 3 tablets) daily and as a maintenance dose approximately 25 to 50 mg propylthiouracil (½ to 1 tablet) daily.

The following side effects may occur frequently (≥ 1/10) with the use of propylthiouracil:

Neutropenia without clinical relevance

Hypersensitivity reactions Gastric intolerance, nausea, vomitingAcute liver toxicity

The use of propylthiouracil may be associated with acute liver failure and death. There are reports of cases in pregnant women, adults and children. Therefore, caution should be exercised when using it, especially in the first six months after starting therapy. As the onset is unpredictable and variable, regular monitoring is not recommended.

Patients should be informed of the possible symptoms and consult a doctor in the event of anorexia, itching, pain in the right upper quadrant, nausea, vomiting, pale stools and dark urine. If these symptoms occur for the first time, the medication must be discontinued and a blood count carried out.

Agranulocytosis: Propylthiouracil may cause agranulocytosis, a potentially life-threatening event, in 0.2 to 0.5% of cases. Patients should be instructed to report any symptoms suggestive of pancytopenia such as: fever, sore throat or interstitial pneumonitis. The risk is highest in the first three months of treatment.

Propylthiouracil and dermatological ADRs

• Drug-induced lupus erythematosus (see below lupus erythematosus subacute-cutaneous)
• Vasculitides: Vasculitides often prove to be ANCA positive (see also ANCA-positive vasculitides). Remark: Many patients develop ANCAs but only about 25% of them develop a vasculopathy. A high percentage of ANCAs remain positive even after the symptoms have healed. Around 10% of patients also develop ANAs). There are indications that on the one hand these are occluding vasculitides (see vasculopathies below). On the other hand, leukocytoclastic vasculitides are also observed. The incidence of vasculitic phenomena is given as 1,10,000 (Burg MR et al. 2025). The average duration of therapy with PTU until vasculitis occurs is stated to be around 42 months. Neutrophil extracellular traps(NETs), which consist of DNA, meyloperoxidase (MPO) and antimicrobial proteins, could play a role in the pathogenesis of this vasculopathy. Apparently, PTU alters the three-dimensional structure of the NETs formed so that their degradation by DNase I is inhibited. This prolongs the presentation of neutrophil enzymes such as MPO or proteinase 3 (see PRTN3 gene below) to the immune system, which may facilitate the occurrence of autoantibodies such as MPO-ANCA. Clinical manifestations include livedo symptoms, ulcers, fever, arthralgia, fatigue and weight loss. The combination with other organ changes (kidney, lung) can lead to life-threatening clinical pictures.
• Allergic skin symptoms: pruritus, urticaria.

Coumarins (oral): Propylthiouracil inhibits vitamin K activity and thus enhances the effect of oral anticoagulants. Therefore, PT/INR monitoring is required with concomitant use.

Beta-blockers, digitalis and theophylline: Patients with hyperthyroidism show increased clearance of these drugs. If the patient becomes euthyroid, a reduction in the dose of beta-blockers and theophylline is required.

Propylthiouracil must not be used in patients with known hypersensitivity to the active substance or a drug component. Caution is advised in patients with impaired liver function or myelosuppression and in pediatric patients.

^Propycil®

1. Burg MR et al. (2025) Occlusive cutaneous vasculopathies: rare differential diagnoses. J Dtsch Dermatol Ges 23:487-506.