Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 10 - 12 May 2023

News 12/05/2023

Review of hydroxyprogesterone started

EMA has started a review of medicines containing hydroxyprogesterone following concerns about the safety and effectiveness of these medicines. In the EU, these medicines are available as hydroxyprogesterone caproate and are given as injections to prevent pregnancy loss or premature birth in pregnant women. In some countries they are also authorised for the treatment of various gynaecological disorders, including disorders caused by the lack of a hormone called progesterone.

EMA’s safety committee (PRAC) started this review due to concerns about results from a study1 which suggested that people who were exposed to hydroxyprogesterone caproate in the womb may have an increased risk of cancer compared with those who were not. The risk seemed to increase when the medicine was used during the first trimester of pregnancy and with the number of injections given. The use of hydroxyprogesterone during the second or third trimester appeared to further increase the risk of cancer for males but not for females.

In addition, results from a second studysuggested that hydroxyprogesterone caproate is no more effective than placebo in preventing recurrent premature birth or medical complications due to prematurity in the newborn infant.

As a result of these concerns, the French medicines agency (ANSM) requested the PRAC to review the risks and benefits of these medicines in all their approved uses and to issue a recommendation on whether their marketing authorisations should be maintained, varied, suspended or withdrawn across the EU.

More information on the review is available here.

Fluoroquinolone antibiotics: reminder of measures to reduce the risk of long-lasting, disabling and potentially irreversible side effects

The PRAC is reminding healthcare professionals that the use of fluoroquinolone antibiotics given by mouth, injection or inhalation, is restricted due to the risk of disabling, long-lasting and potentially irreversible side effects.

These restrictions were introduced in 2019 following an EU-wide review of these very rare but serious side effects. An EMA-funded study3 has shown that although the use of fluoroquinolone antibiotics has decreased, these medicines may still be prescribed outside of their recommended uses.

Restrictions on the use of fluoroquinolone antibiotics mean that they should NOT be used:

  • to treat infections that might get better without treatment or are not severe (such as throat infections);
  • to treat non-bacterial infections, e.g. non-bacterial (chronic) prostatitis;
  • for preventing traveller’s diarrhoea or recurring lower urinary tract infections (urine infections that do not extend beyond the bladder);
  • to treat mild or moderate bacterial infections unless other antibacterial medicines commonly recommended for these infections cannot be used.

The study, which evaluated data from the primary care setting in six European countries (Belgium, France, Germany, the Netherlands, Spain and the United Kingdom) between 2016 and 2021, suggests that the measures taken to restrict the use of these medicines as a result of the EU-wide review had a modest impact.

The content of a direct healthcare professional communication (DHPC) is described in the section ‘New safety information for healthcare professionals’.

More information on the review is available here.

New safety information for healthcare professionals

As part of its advice on safety-related aspects to other EMA committees, the PRAC discussed direct healthcare professional communications (DHPCs) containing important information on fluoroquinolone antibiotics, Gavreto and Voxzogo.

Fluoroquinolone antibiotics: reminder of measures to reduce the risk of long-lasting, disabling and potentially irreversible side effects4

This DHPC reminds healthcare professionals that fluoroquinolone antibiotics should only be prescribed for their approved indications and after a careful assessment of the benefits and risks in individual patients. The DHPC also reminds healthcare professionals to advise patients of the risk of serious adverse reactions with fluoroquinolone antibiotics as well as of the potential long-lasting and serious nature of these effects.

Patients should immediately contact a physician at the first signs of these serious adverse reactions prior to continuing treatment. Special caution should be taken in patients who concurrently are treated with corticosteroids, in older adults, in patients with renal impairment and in patients who have undergone solid organ transplants, as the risk of fluoroquinolone-induced tendinitis and tendon rupture may be exacerbated in these patients.

Gavreto: measures to minimise increased risk for tuberculosis

This DHPC aims to inform healthcare professionals of the increased risk of tuberculosis and measures to minimise this risk, which was identified following a post-marketing review.

In the EU, Gavreto (pralsetinib) is indicated as monotherapy for the treatment of adult patients with rearranged-during-transfection (RET) fusion-positive advanced non-small cell lung cancer (NSCLC) not previously treated with a RET inhibitor.

Tuberculosis, mostly extrapulmonary, has been reported in patients receiving this medicine. An investigation of global safety data for Gavreto identified nine cases of tuberculosis in patients, of which the majority (7/9) occurred in tuberculosis-endemic regions.

Before starting treatment, patients should be evaluated for active and inactive (latent) tuberculosis, as per local recommendations. In patients with active or latent tuberculosis, standard antimycobacterial therapy should be initiated before treatment with Gavreto is started.

Voxzogo: introduction of a new type of syringe

This DHPC informs healthcare professionals about the introduction of a new type of syringe for Voxzogo (vosoritide), a medicine that is used to treat achondroplasia, a rare disease that affects growth of almost all bones in the body.

From June 2023, the packs will contain new solvent needles and new administration syringes due to supply chain reasons. Since the new syringe uses a different graduation marking, in international insulin units (IU), healthcare professionals should ensure that caregivers and patients are informed about correct dose administration. The product information has been amended to reflect the alternative needle and syringe use. There are no changes to the Voxzogo dose.

The DHPCs for Gavreto and Voxzogo will be forwarded to EMA’s human medicines committee (CHMP). When adopted, the DHPCs will be disseminated to healthcare professionals by the marketing authorisation holders, according to an agreed communication plan, and published on the Direct healthcare professional communications page and in national registers in EU Member States.

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.


3 “Impact of European Union Label Changes for Fluoroquinolone Containing Medicinal Products for Systemic and Inhalation Use” (EUPAS37856)

4This document was amended on 22 May 2023 to clarify that fluoroquinolone antibiotics should only be used in their approved indications rather than as last-line treatment.

PRAC statistics: May 2023

PRAC statistics May 2023


  • Safety signal assessments. A safety signal is information which suggests a new potentially causal association, or a new aspect of a known association between a medicine and an adverse event that warrants further investigation. Safety signals are generated from several sources such as spontaneous reports, clinical studies and the scientific literature. More information can be found under 'Signal management'.
  • Periodic safety update reports, abbreviated as PSURs, are reports prepared by the marketing authorisation holder to describe the worldwide safety experience with a medicine in a defined period after its authorisation. PSURs for medicinal products that contain the same active substance or the same combination of active substances but have different marketing authorisations and are authorised in different EU Member States, are jointly assessed in a single assessment procedure. More information can be found under 'Periodic safety update reports: questions and answers'.
  • Risk management plans, abbreviated as RMPs, are detailed descriptions of the activities and interventions designed to identify, characterise, prevent or minimise risks relating to medicines. Companies are required to submit an RMP to EMA when applying for a marketing authorisation. RMPs are continually updated throughout the lifetime of the medicine as new information becomes available. More information is available under 'Risk-management plans'.
  • Post-authorisation safety studies, abbreviated as PASSs, are studies carried out after a medicine has been authorised to obtain further information on its safety, or to measure the effectiveness of risk-management measures. The PRAC assesses the protocols (aspects related to the organisation of a study) and the results of PASSs. More information can be found under 'Post-authorisation safety studies'.
  • Referrals are procedures used to resolve issues such as concerns over the safety or benefit-risk balance of a medicine or a class of medicines. In a referral related to safety of medicines, the PRAC is requested by a Member State or the European Commission to conduct a scientific assessment of a particular medicine or class of medicines on behalf of the EU. More information can be found under referral procedures.
  • Summary safety reports have been introduced as part of the enhanced safety monitoring of COVID-19 vaccines. Marketing authorisation holders are required to submit these reports to EMA, starting on a monthly basis. Their submission complements the submission of PSURs. For more information see EMA’s pharmacovigilance plan for COVID-19 vaccines

Ongoing referrals




Topiramate – Article-31 referralUnder evaluationPRAC continued its assessment
Pseudoephedrine-containing medicinal products - Article - 31 referralUnder evaluationPRAC continued its assessment

Related content

How useful was this page?

Add your rating
1 rating