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No clear and consistent evidence exists of a difference in risk between plasma-derived and recombinant factor VIII medicines

Following a re-examination procedure, EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) has confirmed its previous conclusion of May 2017 that there is no clear and consistent evidence of a difference in the incidence of inhibitor development between the two classes of factor VIII medicines: those derived from plasma and those made by recombinant DNA technology.

Factor VIII is needed for blood to clot normally and is lacking in patients with haemophilia A. Factor VIII medicines replace the missing factor VIII and help control and prevent bleeding. However the body may develop inhibitors as a reaction to these medicines, particularly in patients starting treatment for the first time. This can block the medicines’ effect, so bleeding is no longer controlled.

Due to the different characteristics of individual products within the two classes, the PRAC reaffirmed that the risk of inhibitor development should be evaluated individually for each medicine, regardless of class. The risk for each product will continue to be assessed as more evidence becomes available.

To reflect the evidence currently available, the PRAC confirmed its recommendations that the prescribing information should be updated to include, as appropriate, inhibitor development as a very common side effect in previously untreated patients, and as an uncommon side effect in previously treated patients. The warning on inhibitor development should be amended to highlight that low levels of inhibitors pose less risk of severe bleeding than high levels.

The PRAC’s final recommendation will now be sent to EMA’s Committee for Medicinal Products for Human Use (CHMP) for the adoption of EMA’s opinion. Further details and information for patients and healthcare professionals will be published at that time.

More detailed information:

Factor VIII

Overdose complex and difficult to manage with modified-release products

Following a review, the European Medicines Agency’s experts in medicines safety have recommended that modified- or prolonged-release paracetamol products (designed to release paracetamol slowly over a longer period than the usual immediate-release products) should be suspended from marketing. This is in view of the risks to patients from the complex way these medicines release paracetamol into the body after an overdose.

Experience has shown that in overdose (particularly at high doses), because of the way the paracetamol in modified-release products is released in the body, the usual treatment procedures developed for immediate-release products are not appropriate. If doctors are not aware modified-release paracetamol has been taken, which affects decisions such as when and for how long to give an antidote, overdose might result in severe liver damage or death. In modified-release products that also contain the painkiller tramadol this could be complicated further because of the additional effects of overdose with tramadol.

In many cases, it may not be known whether an overdose of paracetamol involves immediate-release or modified-release products, making it difficult to decide what type of management is needed. The Committee could not identify means to minimise the risk to patients, or a feasible and standardised way to adapt the management of paracetamol overdose across the EU to allow for treatment of cases that involve modified-release preparations. It concluded on balance that the risk following overdose with these medicines outweighs the advantage of having a longer-acting preparation. The Committee therefore recommended that marketing of modified-release paracetamol medicines should be suspended. Immediate-release paracetamol products, which are not affected by this review, will continue to be available as before.

More information on this is included in the hyperlink below:

Paracetamol-modified release

EMA’s Pharmacovigilance and Risk Assessment Committee (PRAC) has recommended the suspension of the marketing authorisations for four linear gadolinium contrast agents because of evidence that small amounts of the gadolinium they contain are deposited in the brain.

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PRAC concludes assessment of gadolinium agents used in body scans and recommends regulatory actions, including suspension for some marketing authorisations

EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) is reviewing the safety of Uptravi (selexipag), following the deaths of 5 patients taking the medicine in France. Based on a preliminary review of available data, EMA advises that Uptravi may continue to be used, but use must be in line with the current prescribing information.

The PRAC will further explore all available data. Once the review is completed, final conclusions will be published.

More information:

EMA reviewing safety of Uptravi for pulmonary arterial hypertension (updated)

EMA’s Pharmacovigilance Risk Assessment Committee (PRAC) is warning that an increase in cases of lower limb amputation (mostly affecting the toes) has been observed in patients taking the type 2 diabetes medicine canagliflozin compared with those taking placebo (a dummy treatment) in two clinical trials, CANVAS and CANVAS-R. The studies, which are still ongoing, involved patients at high risk of heart problems.

More information on the following link:

PRAC concludes that diabetes medicine canagliflozin may contribute to risk of toe amputation

Use of metformin to treat diabetes now expanded to patients with moderately reduced kidney function

Recommendations for patients with kidney impairment updated in product information

The European Medicines Agency (EMA) has concluded that metformin-containing medicines can now be used in patients with moderately reduced kidney function (GFR [glomerular filtration rate]=30–59 ml/min) for the treatment of type 2 diabetes. The product information for these medicines will be updated to revise the current contraindication and give information about doses, monitoring and precautions in patients with reduced kidney function.

The recommendations are the result of a review by EMA of metformin-containing medicines following concerns that current scientific evidence does not justify a contraindication in patients with moderate reduction of kidney function. The current product information also varies between countries and products in the EU and is no longer consistent with clinical guidelines.

More information on the following hyperlink:

Use of metformin to treat diabetes now expanded to patients with moderately reduced kidney function

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