Advagraf 0.5-mg Capsules Recalled by EMA

Lara C. Pullen, PhD


October 21, 2011

October 21, 2011 — The European Medicines Agency agreed to a precautionary recall of Advagraf (tacrolimus; Astellas Pharma Canada) 0.5-mg capsule (yellow and orange) batches because of possible safety concerns.

Advagraf is an immunosuppressant prescribed to prevent the rejection of transplanted liver, kidney, heart, or other organ. It is also used to treat organ rejection when other medicines have not worked. Advagraf is a prolonged release form of tacrolimus and is available in several doses: 0.5 mg, 1 mg, and 5 mg. Patients who have any concerns should speak to their doctor or pharmacist.

The European Medicines Agency has agreed to the immediate recall of some batches of 0.5-mg prolonged-release hard capsules of Advograf from pharmacies and wholesalers across the European Union. Batches being recalled include 0M3006A, 0M3006F, 0M4006K, 0M3006P, 0M4006N, 0M4006E, 0M4006C, 0M6006T, 0M4006L, 0M4006B, 0M4006R, and 0M3006M. According to the information provided to the European Medicines Agency, the affected batches were distributed to several countries across the European Union, including the United Kingdom and Romania.

Capsules from these batches may release more active substance than expected. The defect was detected during routine testing by the marketing-authorization holder, Astellas.

The available information does not suggest that the defect is linked to clinical adverse events. Doctors are advised, however, to consider the potential effect on blood tacrolimus levels when monitoring patients who may have taken capsules from the defective batches, especially those taking maintenance therapy with a daily dose of 0.5 mg. Raised blood levels of the medicine may also occur in patients who also take medicines that slow the breakdown of tacrolimus in the body (ie, the antifungal medicine fluconazole or the protease inhibitor ritonavir).

The Agency's Committee for Medicinal Products for Human Use and Pharmacovigilance Working Party have agreed to the texts of letters to pharmacists and prescribers explaining the recall, and these letters should be sent out within the next few days.

The recall is not expected to affect the overall supply of Advagraf.