The European Medicines Agency has agreed to the immediate recall of some batches of 0.5 mg prolonged-release hard capsules of Advagraf® (tacrolimus) from pharmacies and wholesalers across the European Union (EU). The decision follows detection of more active substance than expected being released from the capsules, although the available information does not suggest that the defect is linked to clinical adverse events. However, the recall is being conducted as a precautionary measure because the defect could have led to slightly higher levels of tacrolimus in the blood of patients taking the affected capsules.

According to the information provided to the EMA, the affected batches were distributed to a number of countries across the EU and Romania and the United Kingdom are estimated to have the most stock of affected capsules remaining. The defective batches listed in the EMA’s press release are as follows:

0M3006A, 0M3006F, 0M4006K, 0M3006P, 0M4006N, 0M4006E, 0M4006C, 0M6006T, 0M4006L, 0M4006B, 0M4006R and 0M3006M

The recall is not expected to affect the overall supply of Advagraf. It only affects batches derived from one parent batch of Advagraf 0.5 mg prolonged-release hard capsules. The company (Astellas) has informed the EMA that replacement batches are available.

The EMA is advising doctors to consider the potential impact 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 tacrolimus may also have occurred in patients also taking medicines that inhibit the metabolism of tacrolimus in the body, such as fluconazole or protease inhibitors for HIV infection including ritonavir.

The EMA press release notes that the Agency’s Committee for Medicinal Products for Human Use (CHMP) and Pharmacovigilance Working Party (PhVWP) have agreed to the texts of letters to pharmacists and prescribers explaining the recall. Astellas will be sending these letters within the next few days.