In accordance with paragraph 8 of Section IV of the Procedure for Expert Evaluation, the applicant must amend the instructions for medical use of the medicinal product upon receipt of new data, including bringing the instructions for medical use into line with the approved instructions for medical use of the original (reference) medicinal product, and ensure that the information on the medicinal product corresponds to current scientific knowledge.
The European Medicines Agency (EMA) has started a review of medicinal products containing hydroxyprogesterone because of concerns about the safety and efficacy of these medicinal products. In the European Union (EU), these medicinal products are available in the form of hydroxyprogesterone caproate and are administered by injection to prevent pregnancy loss or preterm birth in pregnant women. In some countries they are also authorized for the treatment of various gynecological conditions, including disorders caused by a lack of the hormone progesterone.
The Pharmacovigilance Risk Assessment Committee (PRAC) started this review because of concerns about the results of a study1 that showed that people who were exposed in utero to hydroxyprogesterone caproate may have an increased risk of developing cancer compared with those who were not exposed. The risk increased when the medicinal product was used during the first trimester of pregnancy and with a greater number of injections. Use of hydroxyprogesterone caproate during the second or third trimester was found to increase the risk of cancer even more in males, but not in females.
In addition, the results of the second study2 showed that hydroxyprogesterone caproate (hydroxyprogesterone caproate) is no more effective than placebo in preventing recurrent preterm birth or medical complications in newborns caused by prematurity.
In this regard, the French National Agency for the Safety of Medicines and Health Products (ANSM) asked the PRAC to review the risks and benefits of using the medicinal products in all authorized indications and to provide a recommendation on maintaining, varying, suspending, or revoking the authorizations for the use of these medicinal products in the territory of the EU.
After the review is completed, EMA will communicate the PRAC recommendations.
1 Murphy CC, et al. In utero exposure to 17α-hydroxyprogesterone caproate and risk of cancer in offspring. Am J Obstet Gynecol. 2022 Jan;226(1):132.e1-132.e14. doi:10.1016/j.ajog.2021.10.035
2 Blackwell, S. C. et al. 17-OHPC to prevent recurrent preterm birth in singleton gestations (PROLONG Study): A multicenter, international, randomized double-blind trial. Am J Perinatol. 2020 Jan;37(2):127-136. doi:10.1055/s-0039-3400227
More about the medicinal product
Hydroxyprogesterone caproate is a synthetic form of natural hydroxyprogesterone, which is formed in the body from progesterone. Progesterone is involved in preparing the endometrium (the lining of the uterus) for pregnancy and maintaining it during pregnancy. Hydroxyprogesterone caproate attaches to receptors (targets) on cells to which progesterone normally binds. It is expected to reduce the risk of pregnancy loss or preterm birth in pregnant women and to help treat certain gynecological disorders associated with progesterone deficiency, such as menstrual cycle disorders.
Hydroxyprogesterone caproate is available as a solution for injection. In EU countries, this medicinal product is currently available in Austria, France and Italy under the trade names Proluton Depot, Progesterone Retard Pharlon and Lentogest.
More about the procedure
The review of medicinal products containing hydroxyprogesterone was initiated at the request of France, pursuant to Article 31 of Directive 2001/83/EC.
The review is being conducted by the PRAC, the committee responsible for assessing safety issues of medicinal products for human use, which will provide a number of recommendations. Since all medicinal products containing hydroxyprogesterone are registered through the decentralized procedure, the PRAC recommendations will be sent to the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh), which will adopt the relevant position. The CMDh is a body representing the EU Member States, as well as Iceland, Liechtenstein and Norway. It is responsible for ensuring harmonized safety standards for medicinal products authorized through national procedures in the EU.
Перелік лікарських засобів, що містять гідроксипрогестерон (hydroxyprogesterone) та дозволені до медичного застосування в Україні (за даними Державного реєстру лікарських засобів станом на 29.05.2023).
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