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EMA’s safety committee (PRAC) is recommending new measures to avoid dosing errors that have led to some patients incorrectly taking methotrexate-containing medicines daily instead of weekly.

The new measures include restricting who can prescribe these medicines, making warnings on the packaging more prominent and providing educational materials for patients and healthcare professionals. In addition, to help patients follow the once-weekly dosing, methotrexate tablets for weekly use will be provided in blister packs and not in bottles (or tubes).

Methotrexate is used for treating both inflammatory diseases and cancers. When used for inflammatory diseases, such as arthritis and psoriasis, it is taken once a week but for some types of cancer, a much higher dosage is needed and the medicine is taken more frequently. Mistakes in prescribing or dispensing methotrexate as well as misunderstandings of the dosing schedule have led to patients taking the medicine daily instead of weekly for inflammatory diseases, with serious consequences, including fatalities

Мore information:

https://www.ema.europa.eu/en/medicines/human/referrals/methotrexate-containing-medicinal-products

Concerning confirmed cases of WNV for 2018 in neighbouring countries (Romania, Greece) , Bulgarian Drug Agency as the Competent authorities with regard to the activities of blood establishments and blood banks for collection, testing, processing, storage and distribution of human blood and blood components, consider the set up of the following measures as indispensable:

1.Strengthen surveillance of donor selection through extensive clinical examination and interviews, and especially for the residents and visitors of the affected areas and areas with high risk of mosquito bites - rivers, lakes, reservoirs.

2.Increasing awareness of the staff in blood establishments and blood banks and especially in the regions along Danube river and West border region along Struma river.

3.The donors will be required to inform Blood Establishmets and blood banks, if within a period of 15 days after donation he/she found the appearance of a febrile episodes or skin rush.

4.Temporary deferral of potential donors doubtful for disease for 28 days after leaving the areas with high risk of mosquito bites - rivers, lakes, reservoirs or flu-like symptoms pass away. ( for the period between June and October ).

The measures will be in force between June and October 2019.

Regular liver function testing required during treatment

The PRAC has completed its review of Esmya (ulipristal acetate), used to treat moderate to severe symptoms of uterine fibroids (benign tumours of the womb), following reports of serious liver injury.

After considering all the evidence, the PRAC concluded that the medicine must not be used in women with liver problems and that certain other patients may start new treatment courses provided they have regular liver tests. In addition, PRAC recommended that Esmya should be used for more than one treatment course only in women who are not eligible for surgery.

The PRAC’s recommendations will now be forwarded to the Committee for Medicinal Products for Human Use (CHMP) for the adoption of EMA’s final opinion, and this will then go to the European Commission for a final legal decision. A letter will be sent to doctors to inform them of the new restrictions of use, which will become applicable after a Commission decision is issued.

More information:

PRAC recommends new measures to minimise risk of rare but serious liver injury with Esmya for fibroids

The European Medicines Agency (EMA) has started a review of the risk of dosing errors with methotrexate medicines. When used for inflammatory diseases, such as arthritis and psoriasis, methotrexate is taken once a week whereas for some types of cancer, the dose is higher and the medicine is used more frequently. Mistakes have led to some patients incorrectly receiving a dose every day instead of every week. As a result, patients have received too much of the medicine, with serious consequences in some cases.

More information:

Methotrexate containing medicinal products

The European Medicines Agency (EMA) has recommended contraindicating the use of the prostate cancer medicine Xofigo (radium-223 dichloride) with Zytiga (abiraterone acetate) and prednisone/prednisolone, due to an increased risk of death and fractures with this combination.

More information:

Prostate cancer medicine Xofigo must not be used with Zytiga and prednisone/prednisolone

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EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has concluded its review of retinoid1 medicines and has recommended updating the measures for pregnancy prevention and including a warning on the possible risk of neuropsychiatric disorders (such as depression, anxiety and mood changes).

During its review, the PRAC assessed the available data including published literature and post-marketing reports of side effects, and also sought the views of patients and healthcare professionals in a dedicated stakeholder meeting and a successive written consultation.

More information

The PRAC recommendations are summarised below:

Retinoid-containing medicinal products

The European Medicines Agency’s experts in medicines safety, the Pharmacovigilance Risk Assessment Committee (PRAC) are recommending new measures to avoid exposure of babies to valproate medicines in the womb. Babies exposed are at risk of malformations and developmental problems.

More information:

PRAC recommends new measures to avoid valproate exposure in pregnancy

No new patients should start treatment for the time being.

EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) is currently reviewing the benefits and risks with Esmya, following reports of serious liver injury, including liver failure leading to transplantation.

As a temporary measure while the review is ongoing, the PRAC has recommended regular liver monitoring for women taking Esmya for uterine fibroids.

All women taking Esmya should have a liver function test at least once a month during treatment. If the test is abnormal (liver enzyme levels more than 2 times the upper limit of normal), the healthcare professional should stop treatment and closely monitor the patient. Liver tests should be repeated 2 to 4 weeks after stopping treatment.

The PRAC is also recommending that no new patients should be started on Esmya and no patients who have completed a course of treatment should start another one for the time being.

A link between Esmya and cases of serious liver injury is under review. These recommendations are temporary measures to protect patients’ health, pending the conclusion of the review of Esmya which started in December 2017.

More information:

Women taking Esmya for uterine fibroids to have regular liver tests while EMA review is ongoing

Review finds measures to protect patients have not been sufficiently effective

EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has recommended the suspension of the marketing authorisations for hydroxyethyl-starch (HES) solutions for infusion across the European Union. These products are used as plasma volume replacement following acute (sudden) blood loss, where treatment with alternative products known as ‘crystalloids’ alone is not considered to be sufficient.

The review was triggered by results from two drug utilisation studies indicating that HES solutions are being used in critically ill patients and those with sepsis and kidney injury despite restrictions introduced in 2013 to reduce the risks of kidney problems and deaths in these patient populations.

In 2013, the PRAC had recommended restrictions on the use of HES solutions, including that they must no longer be used to treat critically ill patients or patients with sepsis, because of an increased risk of kidney injury and mortality seen in clinical trials. The Committee requested that further studies be carried out to verify adherence to these restrictions.

The PRAC has reviewed the results from the drug utilisation studies of HES solutions for infusion together with the currently available data on benefits and risks from clinical trials and observational studies and feedback received from stakeholders and experts. Based on this review, the PRAC has concluded that the restrictions introduced in 2013 have not been sufficiently effective. The Committee explored the possibility of introducing additional measures but concluded that such measures would be ineffective or insufficient.

In view of the serious risks that certain patient populations are exposed to, the PRAC has recommended the suspension of the marketing authorisations for HES solutions. Alternative treatment options are available.

The PRAC recommendation will now be sent to the Coordination Group for Mutual Recognition and Decentralised Procedures – Human (CMDh)1 for consideration at its meeting on 22-25 January 2018.

For more information:

Hydroxyethyl starch (HES) containing medicinal products


1 The CMDh is a medicines regulatory body representing the European Union (EU) Member States, Iceland, Liechtenstein and Norway.

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