Meeting highlights from the Pharmacovigilance Risk Assessment Committee (PRAC ) 11-15 March 2019

EU referral procedures for safety reasons:

• Just started – review on screening patients before treatment with fluorouracil, capecitabine, tegafur and flucytosine. The review to examine existing screening methods and their value in identifying patients at increased risk of severe side effects.
  • Patients with low DPD can experience severe side effects due to a build-up of fluorouracil.

On-going procedures:

• Methotrexate – JYLAMVO (CAP), NORDIMET (CAP); NAP – EMEA/H/A-31/1463
  • Review of the benefit-risk balance following notification by Spain of a referral under Article 31 of Directive 2001/83/EC, based on pharmacovigilance data

Full meeting highlights can be viewed from this link. (Links to a new website)

New signals detected from other sources

• Levomethadone (NAP), methadone (NAP) -Signal of opioid toxicity in infants exposed to levomethadone and/or methadone via breast milk
• Natalizumab – TYSABRI (CAP) – Signal of psoriasis
• Ondansetron (NAP) – Signal of birth defects following in-utero exposure during the first trimester of pregnancy arising from recent publications
• Pirfenidone – ESBRIET (CAP) – Signal of hyponatraemia
• Pirfenidone – ESBRIET (CAP) – Signal of herpes viral infections
• Sodium-glucose co-transporter 2 (SGLT2) inhibitors: canagliflozin – INVOKANA (CAP); canagliflozin, metformin – VOKANAMET (CAP); dapagliflozin – EDISTRIDE (CAP); dapagliflozin – FORXIGA (CAP); dapagliflozin, Pharmacovigilance Risk Assessment Committee (PRAC) EMA/PRAC/170203/2019 Page 14/60 metformin – EBYMECT (CAP); dapagliflozin, metformin – XIGDUO (CAP); empagliflozin – JARDIANCE (CAP); empagliflozin, metformin – SYNJARDY (CAP); ertugliflozin – STEGLATRO (CAP); ertugliflozin, metformin – SEGLUROMET (CAP) – New information on the known association between sodium-glucose co-transporter 2 (SGLT2) inhibitors and diabetic ketoacidosis (DKA) in surgical patients
• Tocilizumab – ROACTEMRA (CAP) – Signal of drug reaction with eosinophilia and systemic symptoms (DRESS)
• Tofacitinib – XELJANZ (CAP) – Signal of increased risk of pulmonary embolism and overall mortality arising from a post-authorisation safety study in patients with cardiovascular risk factors treated for rheumatoid arthritis with tofacitinib 10 mg twice daily

Signals follow-up and prioritisation

• Apixaban – ELIQUIS (CAP) – EMEA/H/C/002148/SDA/032.1 -Signal of pancreatitis
• Belimumab – BENLYSTA (CAP) – EMEA/H/C/002015/SDA/029.1 – Signal of lupus nephritis
• Nivolumab – OPDIVO (CAP) – EMEA/H/C/003985/SDA/035 – Signal of hypoparathyroidism
• Paracetamol (NAP) – Signal of paracetamol use in pregnancy and child neurodevelopment and effects on the urogenital apparatus
• Paracetamol (NAP) – Signal of paracetamol use during pregnancy and premature ductus arteriosus closure in offspring
• Tocilizumab – ROACTEMRA (CAP) – EMEA/H/C/000955/SDA/053 – Signal of psoriasis