Propylthiouracil

Generic name
Propylthiouracil
Brand name
ATC Code
H03BA02
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Propylthiouracil

Dosages
Side effects in children
Warnings & precautions in children
Contra-indications in children

Interactions
PK
Renal impairment
References

Pharmacokinetics in children

Age Dose Cmax Tmax(h) T1/2 (h) Reference
8-15 years (n=7) ca. 200 mg/m2; range 180-280 mg/m2 - - 1,47 (with hyperthyreodism)
1,53 (with euthyroid status)		 Hoffman 1988
10-17 years (n=6) 10-280 mg/m2 7,2-18 mcg/ml 0,5-1 1,3 ± 0,41 (mean ± SD) Okuno 1983
Adults 50 mg   1-2   SmPC Propycil

Antithyroid drugs are accumulated in the thyroid gland through an active transport mechanism. Although no propylthiouracil is detectable in the serum after 8 hours, the duration of action of a larger single dose is 6 to 8 hours due to the strong accumulation in the thyroid. [SmPC Propycil 50mg]

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

Hyperthyroidism if alternative is not possible
  • Oral
    • 1 month up to 10 years
      • Initial dose: 5 - 7 mg/kg/day in 3 doses. Max: 300 mg/day. Until euthyroid status is achieved.
        Maintenance dose: Adjust the maintenance dosage based on the hormone levels or add levothyroxine.

      • Under 10 years of age, there is little evidence about the optimum and safe doses. Read the warnings and precautions for use in children before administering.

    • 10 years up to 12 years
      [11] [12]
      • Initial dose: 75 - 225 mg/day in 3 doses. 100–300 mg/day orally in 4 doses can possibly be given (observe a dosing interval of 6 hours strictly)
        Until euthyroid status is achieved.
        Maintenance dose: Adjust the maintenance dosage based on the hormone levels or add levothyroxine.
    • 12 years up to 18 years
      [11] [12]
      • Initial dose: 225 - 300 mg/day in 3 doses. 300–400 mg/day orally in 4 doses can possibly be given (observe a dosing interval of 6 hours strictly)
        Until euthyroid status is achieved.
        Maintenance dose: Adjust the maintenance dosage based on the hormone levels or add levothyroxine..
Hyperthyroidism
  • Oral
    • 6 months up to 6 years
      • Initial dose: 5 - 10 mg/kg/day in 3 doses. Max: 300 mg/day. Until euthyroid status is achieved.
        Maintenance dose: Adjust the dosage based on the hormone levels or add levothyroxine.

      • Under 6 years of age, there is little evidence about the optimum and safe doses. Read the warnings and precautions for use in children before administering.

    • 6 years up to 10 years
      • Initial dose: 50 - 150 mg/day in 3 doses. Until euthyroidism is achieved.
      • Maintenance dose: 25 - 50 mg/day in 2 - 3 doses. Adjust dose based on hormone levels or add levothyroxine.
    • 10 years up to 18 years
      • Initial dose: 100 - 300 mg/day in 3 doses. Until euthyroidism is achieved.
        In severe cases and after iodine contamination, higher initial doses of 300 mg to 600 mg daily in 4-6 doses are recommended.
      • Maintenance dose: 50 - 150 mg/day in 2 - 3 doses. Adjust dose based on hormone levels or add levothyroxine..

Renal impaiment in children > 3 months

GFR ≥10 ml/min/1.73m2: Dose adjustment not required.

GFR <10 ml/min/1.73m2: A general recommendation on dose adjustment cannot be provided.

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

Propylthiouracil can lead to liver damage and acute liver failure which can be fatal [Yu 2020; Sato 2011;  Andriana 2013, Rivkees 2009]

Agranulocytosis in children has been reported by Minimatani et al. 2011.  This was dose-dependent in patients treated with methimazole and propylthiouracil  (7-85 years, median 32 years)  [Yoshimura Noh 2024].

Skin rash, Rash with arthralgias, arthritis with purpura and hematuria, elevation in liver enzymes and neutropenia was reported in children [Glaser 2008]

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

Because of the increased risk of serious and fatal liver damage, it should not be used in children unless other therapies are not possible or not tolerated {FDA Back box warning 2011; Karras 2011; Malazowski 2010]; This also applies to adults, but the effects are more prominent in children [Rivkees 2009]. Primarily observed at doses of 300 mg/day upwards, but in some cases already at just 50 mg/day [Yu 2020].

If propylthiouracil is indicated due to the lack of alternatives, monitoring of liver function and symptoms of liver damage is required, particularly during the first 6 months after starting treatment.

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

ANTITHYROID PREPARATIONS

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

Sulfur-containing imidazole derivatives
H03BB01
H03BB02

References

  1. Hoffman WH, et al, Pharmacokinetics of propylthiouracil in children and adolescents with Graves' disease in the hyperthyroid and euthyroid states, Dev Pharmacol Ther, 1988, 11(2), 73-81
  2. FDA, Black box warning propylthiouracil, http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm164162.htm
  3. Gao Y, et al, Long-term outcomes of patients with propylthiouracil-induced anti-neutrophil cytoplasmic auto-antibody-associated vasculitis, Rheumatology (Oxford)., 2008, Oct;47(10), 1515-20
  4. Glaser NS, et al, Organization of Pediatric Endocrinologists of Northern California Collaborative Graves' Disease Study G. Predicting the likelihood of remission in children with Graves' disease: a prospective, multicenter study, Pediatrics, 2008, Mar;121(3), e481-8
  5. Gorton C, et al, Remission in children with hyperthyroidism treated with propylthiouracil. Long-term results, Am J Dis Child, 1987, Oct;141(10), 1084-6
  6. Karras S, et al, Toxicological considerations for antithyroid drugs in children, Expert Opin Drug Metab Toxicol., 2011, Apr;7(4), 399-410
  7. Lian XL, et al, [The clinical characteristics of symptomatic propylthiouracil-induced hepatic injury in patients with hyperthyroidism], Zhonghua Nei Ke Za Zhi, 2004, Jun;43(6), 442-6
  8. Malozowski S, et al, Propylthiouracil-induced hepatotoxicity and death. Hopefully, never more. . , J Clin Endocrinol Metab, 2010, Jul;95(7), 3161-3
  9. Rivkees SA, et al, Dissimilar hepatotoxicity profiles of propylthiouracil and methimazole in children, J Clin Endocrinol Metab, 2010 , Jul;95(7), 3260-7
  10. Sato H, et al, Comparison of methimazole and propylthiouracil in the management of children and adolescents with Graves' disease: efficacy and adverse reactions during initial treatment and long-term outcome., J Pediatr Endocrinol Metab, 2011, 24(5-6), 257-63
  11. Aurobindo Pharma B.V, SmPC Propylthiouracil (RVG 52546) 04-01-2024, www.geneesmiddeleninformatiebank.nl
  12. Admeda Artzneimittel GmHB, SmPC Propycil (6075593.00.00), 09/2019
  13. Malozowski S, et al, Propylthiouracil-induced hepatotoxicity and death. Hopefully, never more. ., J Clin Endocrinol Metab, 2010, Jul;95(7), 3161-3
  14. Rivkees SA, et al, Dissimilar hepatotoxicity profiles of propylthiouracil and methimazole in children, J Clin Endocrinol Metab, 2010, Jul;95(7), 3260-7
  15. Rivkees SA, Mattison DR., Propylthiouracil (PTU) Hepatoxicity in Children and Recommendations for Discontinuation of Use., Int J Pediatr Endocrinol., 2009, 132041
  16. Minamitani K, et al., A Report of Three Girls with Antithyroid Drug-Induced Agranulocytosis; Retrospective Analysis of 18 Cases Aged 15 Years or Younger Reported between 1995 and 2009, Clin Pediatr Endocrinol., 2011, 20(2), 39-46
  17. Yoshimura Noh J, et al., Dose-dependent incidence of agranulocytosis in patients treated with methimazole and propylthiouracil., Endocr J., 2024, 71(7), 695-703
  18. Okuno A, et al., Pharmacokinetics of propylthiouracil in children and adolescents with Graves disease after a single oral dose., Pediatr Pharmacol (New York)., 1983, 3(1), 43-7
  19. Andriana N, et al., Adverse events related with propylthiouracil therapy of Graves’ Disease in children at Cipto Mangunkusumo Hospital Jakarta., Int J Pediatr Endocrinol., 2013, 139
  20. Yu W, et al., Side effects of PTU and MMI in the treatment op hyperthyroidism: a systematic review and meta-analysis, Endocr Pract., 2020, 26(2), 207-17
  21. Dötsch J, et al., Diagnosis and management of juvenile hyperthyroidism in Germany: a retrospective multicenter study., J Pediatr Endocrinol Metab., 2000, 13(7), 879-85
  22. Marques O, et al., Treatment of Graves' disease in children: The Portuguese experience., Endocrinol Diabetes Nutr (Engl Ed)., 2018, 65(3), 143-9
  23. Sato H, et al., Clinical features at diagnosis and responses to antithyroid drugs in younger children with Graves' disease compared with adolescent patients., J Pediatr Endocrinol Metab., 2014, 27(7-8), 677-83
  24. Lippe BM, et al., Hyperthyroidism in children treated with long term medical therapy: twenty-five percent remission every two years., J Clin Endocrinol Metab., 1987, 64(6), 1241-5

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Overdose