Kommersiellt obunden läkemedelsinformation riktad till läkare och sjukvårdspersonal

Propyltiouracil

Klassificering: A

Preparat: Propycil, Tiotil

ATC kod: H03BA02

Substanser: propyltiouracil

Sammanfattning

Tyreostatiska läkemedel kan orsaka agranulocytos, som enligt vissa studier är vanligare hos kvinnliga patienter.
Propyltiouracil är rekommenderat under gravididet, men på grund av risk för levertoxicitet hos modern ska lägsta dos användas.
 

Additional information

Pharmacokinetics and dosing

No studies with a clinically relevant sex analysis regarding the pharmacokinetics or dosing of propylthiouracil have been found. For both men and women, the lowest effective dose is recommended (see Adverse effects) [3]. There is no evidence that the pharmacokinetics of propylthiouracil in pregnant and non-pregnant women differs [9]. 

Effects

Studies have shown that more men than women fail to enter long-term remission after thyreostatic therapy for Graves’ disease [1,2]. A clinical trial (92 men, 444 women) found that men had a markedly worse outcome after medical treatment with carbimazole (prodrug to methimazole) or propylthiouracil for 18 months. Men had with a remission rate of only 19.5% compared with 40% for females [1].

Adverse effects

Antithyroid drug therapy is associated with agranulocytosis. Among reported cases of antithyroid-induced agranulocytosis, women are in majority [3-5]. Mean doses at onset of agranulocytosis are varying; for methimazole 25-44 mg/day and for propylthiouracil 217-383 mg/day. Although antithyroid-induced agranulocytosis is rare, it has been suggest that low-dose methimazole therapy may be safer than high-dose therapy or treatment with conventional doses of propylthiouracil [3]. The reasons why women are affected more frequently than men are suggested to be due to pharmacokinetic differences between men and women, immunologic and hormonal factors as well as differences in co-medications [6].

Reproductive health issues

Some epidemiologic studies suggest that methimazole exposure during the first trimester of pregnancy is associated with an increased risk of congenital malformations. Since propylthiouracil has not been associated with an increased risk of congenital malformations, this is the recommended drug during the first trimester during pregnancy. However, propylthiouracil is associated with hepatotoxicity (estimated incidence 0.1-0.2% of exposed adults), and therefore treatment with low-dose methimazole during the second and third trimesters have been suggested by American guidelines [7], but not in Sweden [8]. Treatment of thyrotoxicosis during pregnancy should always be referred to a specialist.Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).

Försäljning på recept

Fler kvinnor än män hämtade ut tabletter innehållande propyltiouracil (ATC-kod H03BA02) på recept i Sverige år 2015, totalt 971 kvinnor och 127 män [10].,,Prevalensen av hypertyreos är 2 % hos kvinnor och 0,2 % hos män [6].

Uppdaterat: 2017-03-31

Litteratursökningsdatum: 2014-10-06

Referenser

  1. Allahabadia A, Daykin J, Holder RL, Sheppard MC, Gough SC, Franklyn JA. Age and gender predict the outcome of treatment for Graves' hyperthyroidism. J Clin Endocrinol Metab. 2000;85:1038-42. PubMed
  2. Cinemre H, Bilir C, Gokosmanoglu F, Akdemir N, Erdogmus B, Buyukkaya R. Predictors of time to remission and treatment failure in patients with Graves' disease treated with propylthiouracil. Clin Invest Med. 2009;32:E199-205. PubMed
  3. Cooper DS, Goldminz D, Levin AA, Ladenson PW, Daniels GH, Molitch ME et al. Agranulocytosis associated with antithyroid drugs Effects of patient age and drug dose. Ann Intern Med. 1983;98:26-9. PubMed
  4. Tajiri J, Noguchi S, Murakami T, Murakami N. Antithyroid drug-induced agranulocytosis The usefulness of routine white blood cell count monitoring. Arch Intern Med. 1990;150:621-4. PubMed
  5. Nakamura H, Miyauchi A, Miyawaki N, Imagawa J. Analysis of 754 cases of antithyroid drug-induced agranulocytosis over 30 years in Japan. J Clin Endocrinol Metab. 2013;98:4776-83. PubMed
  6. Vera Regitz-Zagrosek. Sex and Gender Differences in Pharmacology. Springer-Verlag Berlin Heidelberg; 2012.
  7. Cassina M, Donà M, Di Gianantonio E, Clementi M. Pharmacologic treatment of hyperthyroidism during pregnancy. Birth Defects Res A Clin Mol Teratol. 2012;94:612-9. PubMed
  8. Tiamazol (Thacapzol). Kloka Listan 2014. Expertråd Endokrinologiska och metabola sjukdomar. [updated 2013-12-11, cited 2014-10-13]. länk
  9. Clark SM, Saade GR, Snodgrass WR, Hankins GD. Pharmacokinetics and pharmacotherapy of thionamides in pregnancy. Ther Drug Monit. 2006;28:477-83. PubMed
  10. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-05.] länk

Författare: Linnéa Karlsson Lind, Desirée Loikas

Faktagranskat av: Mia von Euler

Godkänt av: Karin Schenck-Gustafsson