Hydroxyprogesterone Caproate – Effectiveness Reviewed By EMA

The European Medicines Agency (EMA) has initiated a review of medications containing hydroxyprogesterone due to concerns regarding their safety and efficacy. These medications, known as hydroxyprogesterone caproate, are administered via injections to prevent pregnancy loss or premature birth in pregnant women. They are also authorized in certain countries to treat various gynaecological disorders related to progesterone deficiency.

The EMA’s safety committee, PRAC, has initiated a review in response to concerns regarding increased cancer risk associated with hydroxyprogesterone caproate exposure in utero. The risk appeared to be heightened when the medication was used during the first trimester of pregnancy and with a higher number of injections. Additionally, the use of hydroxyprogesterone during later stages of pregnancy seemed to elevate cancer risk in males but not in females. Furthermore, hydroxyprogesterone caproate is not more effective than a placebo in preventing recurrent premature birth or medical complications related to prematurity in newborn infants.

In light of these concerns, the French medicines agency (ANSM) has asked the PRAC to evaluate the risks and benefits of these medications in their authorized applications and offer guidance on whether their marketing authorizations in the European Union should be retained, altered, paused, or revoked.

The PRAC is advising healthcare professionals to be cautious about the limited use of fluoroquinolone antibiotics when given orally, through injection, or inhalation due to the potential risk of long-lasting and potentially irreversible side effects that can lead to disability. These usage restrictions were put in place in 2019 after an extensive review conducted throughout the European Union recognized these rare but serious side effects. Although there has been a decline in the use of fluoroquinolone antibiotics, these medications may still be prescribed for purposes that are not in line with their recommended uses. Restrictions on fluoroquinolone antibiotics usage prohibit their use in the following cases:

  • Do not use fluoroquinolone antibiotics for non-severe or self-resolving infections like throat infections.
  • Avoid using them for non-bacterial infections, such as non-bacterial (chronic) prostatitis.
  • Avoid prescribing them for preventing traveller’s diarrhoea or recurring lower urinary tract infections that are limited to the bladder.
  • Reserve fluoroquinolones for severe bacterial infections when other recommended antibiotics are not suitable for use.

The restrictions placed on these medicines as a result of the EU-wide review had a limited impact, according to the data collected from primary care settings in six European countries (Germany, Belgium, the Netherlands, Spain, France, and the United Kingdom) from 2016 to 21. The ‘New safety information for healthcare professionals’ section of the direct healthcare professional communication (DHPC) provides details on the updated information.

The PRAC, while providing safety-related advice to other committees within the EMA, addressed the topic of direct healthcare professional communications (DHPCs), containing important information on the following.

Fluoroquinolone antibiotics

In a DHPC addressed to healthcare professionals, it is reiterated that fluoroquinolone antibiotics should only be prescribed within approved indications and after a careful assessment of individual patients’ risks and benefits. The communication emphasizes the need for healthcare professionals to inform patients about the potential for serious adverse reactions associated with fluoroquinolones, as well as the long-lasting and severe nature of these effects. Patients are advised to promptly seek medical attention at the first signs of such adverse reactions before continuing treatment. Additionally, special caution is advised when prescribing fluoroquinolones to patients concurrently receiving corticosteroids, older adults, individuals with renal impairment, or those who have undergone solid organ transplants, as these populations may face an increased risk of fluoroquinolone-induced tendinitis and tendon rupture.


This DHPC provides healthcare professionals with information regarding the introduction of a new syringe for Voxzogo (vosoritide), a medication used for treating achondroplasia, a rare disorder affecting bone growth in the body. Due to supply chain reasons, starting in June 2023, Voxzogo packs will include new solvent needles and administration syringes. It is important for healthcare professionals to note that the new syringe has different graduation markings in international insulin units (IU), requiring them to inform caregivers and patients about the correct administration of doses. The product information has been updated to reflect the use of the alternative needle and syringe, while the Voxzogo dosage remains unchanged. The DHPCs for Gavreto and Voxzogo will be submitted to EMA’s human medicines committee (CHMP) and, upon adoption, will be disseminated to healthcare professionals by the marketing authorization holders according to an agreed communication plan. These DHPCs will also be published on the Direct healthcare professional communications page and in national registers across EU Member States.


This DHPC informs healthcare professionals about the elevated tuberculosis risk associated with Gavreto (pralsetinib) and provides mitigation measures. Gavreto is approved as a monotherapy for treating advanced non-small cell lung cancer (NSCLC) in adult patients with rearranged-during-transfection (RET) fusion, who have not been previously treated with a RET inhibitor. Instances of tuberculosis, primarily affecting areas outside the lungs, have been reported among patients using this medication. A global analysis of safety data associated with Gavreto revealed nine cases of tuberculosis in patients, with the majority (7 out of 9) occurring in regions where tuberculosis is prevalent. Before initiating Gavreto treatment, patients should undergo assessment for active tuberculosis as well as latent tuberculosis, according to local guidelines. Before starting Gavreto treatment, standard antimycobacterial therapy should be initiated if active or latent tuberculosis is detected.