Идентификация

Press release 17/01/2020

EMA’s safety committee (PRAC) has confirmed its recommendation to limit the use of high-strength creams containing 100 micrograms/gram (0.01%) of estradiol to a single treatment period of up to 4‑weeks. This follows a re-examination of its recommendation of October 2019 which was requested by one of the companies that market high-strength estradiol cream.

The PRAC reviewed available data on the safety and effectiveness of high-strength estradiol-containing creams used to treat symptoms of vaginal atrophy in women who have been through menopause. Data on these creams show that in postmenopausal women who use them, the levels of estradiol in the blood were higher than normal postmenopausal levels. The PRAC concluded that absorption of estradiol into the bloodstream is of concern and could result in similar side effects to those seen with hormone replacement therapy (HRT). The side effects of HRT taken orally or used transdermally (as patches) include venous thromboembolism (formation of blood clots in the veins), stroke, endometrial cancer (cancer of the lining of the womb) and breast cancer. In addition, there are limited safety data on long term use of high-strength estradiol creams. For these reasons, the PRAC recommended that these creams should only be used for a single treatment period of a maximum of 4 weeks.

The PRAC recommends that the prescribing information for these creams will be updated with the new recommendations. A warning that the medicine is to be used for a single treatment period of up to 4 weeks only will be placed on the outer and inner packaging and the size of the tube will be limited to 25 grams to prevent use for longer than recommended.

The PRAC recommendations will now be sent to the CMDh to make a decision about their implementation. The CMDh is a body representing EU Member States as well as Iceland, Liechtenstein and Norway.

For more information:

PRAC confirms four-week limit for use of high-strength estradiol creams | European Medicines Agency

EMA’s safety committee (PRAC) recommended restricting Lemtrada for use in adults with relapsing remitting multiple sclerosis that is highly active despite adequate treatment with at least one disease-modifying therapy or if the disease is worsening rapidly with at least two disabling relapses in a year and brain-imaging showing new damage.

The PRAC had issued interim measures on Lemtrada while reviewing reports of serious reactions. The PRAC completed the review and recommended that Lemtrada must no longer be used in in patients with certain heart, circulation or bleeding disorders or in patients who have auto-immune disorders other than multiple sclerosis.

The recommendations reflect PRAC’s review of reports concerning rare but serious effects, including deaths, from immune-mediated conditions (caused by the body’s defence system not working properly) and serious disorders of the heart, circulation and bleeding.

More information is available on the hyperlink below:

Lemtrada for multiple sclerosis: measures to minimise risk of serious side effects

The PRAC concluded that Xeljanz (tofacitinib) could increase the risk of blood clots in the lungs and in deep veins in patients who are already at high risk.

The PRAC recommended that Xeljanz should be used with caution in patients at high risk of blood clots. In addition, the maintenance doses of 10 mg twice daily should not be used in patients with ulcerative colitis who are at high risk unless there is no suitable alternative treatment. Patients older than 65 years of age should be treated with Xeljanz only when there is no other appropriate treatment.

These recommendations follow the PRAC’s review of an ongoing study in patients with rheumatoid arthritis and an increased risk of cardiovascular disease. The study showed an increased risk of blood clots in deep veins and in the lungs with both the 5 mg and 10 mg twice daily doses of Xeljanz as compared with patients taking TNF-inhibitors (medicines that help reduce inflammation).

More information is available on the hyperlink below.

Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC) 28-31 October 2019

Medicine should only be used after two previous treatments or when other treatments cannot be taken

EMA’s safety committee PRAC has recommended restricting the use of the cancer medicine Xofigo (radium-223 dichloride) to patients who have had two previous treatments for metastatic prostate cancer (prostate cancer that has spread to the bone) or who cannot receive other treatments.

These restrictions follow a review of data from a study suggesting that patients given Xofigo seemed to be at risk of dying earlier and had more fractures than patients given placebo (a dummy treatment). The study included patients with no or only mild symptoms, whereas Xofigo is only authorised in patients with symptoms. In the study, patients given Xofigo with Zytiga (abiraterone acetate) and prednisone/prednisolone died on average 2.6 months earlier than those given placebo with Zytiga and prednisone/prednisolone. In addition, 29% of patients who received the Xofigo combination had fractures, compared with 11% of patients given placebo.

It is thought that Xofigo, which is taken up by the bone, accumulates at sites where the bone is already damaged, for example by osteoporosis or micro-fractures, increasing the risk of fracture. However, the reasons for a possible earlier death in this study are not fully understood.

The PRAC also confirmed its previous interim recommendation that the medicine must not be used with Zytiga and prednisone/prednisolone.

More information:

Xofigo

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

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