PRAC May 2020 – New measures to avoid handling errors with Leuprorelin depot medicines and completion of signal evaluation for ibuprofen, ketoprofen and fixed-dose combinations

During its meeting of May 2020, the Pharmacovigilance Risk Assessment Committee (PRAC) of the European Medicines Agency (EMA) recommended measures to avoid handling errors in the preparation and administration of leuprorelin depot medicines.

A review by the PRAC found that handling errors resulted in some patients receiving insufficient amounts of their medicine. The errors reported included incorrect use of the needle or syringe, causing the medicine to leak from the syringe, and failure to inject leuprorelin properly. 

The Committee is therefore recommending that only healthcare professionals familiar with the preparation steps for leuprorelin depot medicines should prepare and administer the medicines to patients. Patients should not prepare or inject these medicines themselves. 

The Committee also made recommendations for particular leuprorelin depot medicines. For the medicine Eligard, the product information is to be updated with warnings to strictly follow the instructions for preparation and administration and to monitor patients if a handling error occurs. In addition, the company marketing Eligard must replace the current device used to administer the medicine with one that is easier to handle by October 2021.  

For another medicine, Lutrate Depot, the PRAC recommended that instructions for handling the medicine be revised to make them easier to follow and its packaging changed so the instructions are easier to find.

Depot formulations of leuprorelin are used to treat prostate cancer, breast cancer, certain conditions that affect the female reproductive system, and early puberty. Several formulations require complex steps to prepare the injection.

Information for patients
Errors in using leuprorelin depot medicines (which are designed to work over a long period) may make treatment less effective.

These medicines should only be prepared and given by a doctor or nurse with experience in using them. You should not prepare or inject these medicines yourself.

If you have concerns about your treatment, please discuss these with your doctor or pharmacist.

Information for healthcare professionals
Leuprorelin depot medicines should only be prepared and given by healthcare professionals who are familiar with the procedures. Patients should not inject the medicine themselves.

These recommendations follow a review of reports of handling errors with depot formulations of leuprorelin medicines, which could result in underdosing and a lack of efficacy.

Handling errors are related to the complexity of the reconstitution process, which involves multiple steps for some leuprorelin depot formulations. Reported handling errors include incorrect use of syringe or needle (causing the medicine to leak from the syringe), inadequate reconstitution, and incorrect injection of the leuprorelin implant.

For Eligard, used to treat advanced hormone-dependent prostate cancer, warnings will be included in the summary of product characteristics to inform healthcare professionals about cases of handling errors and to remind them to strictly follow the instructions for preparation and administration of the medicine. In case of suspected or known handling error with the medicine, patients should be monitored appropriately.

The company that markets Eligard has been asked to modify the device to reduce the high number of preparation steps. This modification will take around 18 months.

Instructions for handling Lutrate Depot will be revised to make them easier to follow and the packaging will be changed to facilitate access to these instructions.

A direct healthcare professional communication (DHPC) will be sent in due course to healthcare professionals prescribing, dispensing or administering the medicine. The DHPC will also be published on a dedicated page on the EMA website.

The following Leuprorelin depot medicine is authorised and marketed in Belgium: Depo-Eligard

Completion evaluation signal for ibuprofen, ketoprofen and fixed-dose combinations for systemic use
In April 2020, the PRAC completed the evaluation of the signal "Ibuprofen, ketoprofen and fixed-dose combinations for systemic use - serious aggravation of infections (EPITT No 19415)". The product information should be updated and marketing authorisation holders of ibuprofen and ketoprofen-containing medicinal products should apply for a variation according to the time period specified in the PRAC Recommendation.

As the approved signal text needs to be adapted at national level to the existing formulations in the product information, marketing authorisation holders are requested to submit a C.I.3.z Type IB variation for this purpose.

Last updated on
26/05/2020