2021 WHO Pharmaceuticals No.3 NEWSLETTER The WHO Pharmaceuticals Newsletter provides you with the latest information on the safety of medicines WHO Vision for Medicines Safety and legal actions taken by regulatory authorities around No country left behind: the world. It also provides signals based on information worldwide pharmacovigilance for safer medicines, safer patients derived from the WHO global database of individual case safety reports, VigiBase. The aim of the Newsletter is to disseminate regulatory information on the safety of pharmaceutical products, based on communications received from our network of national pharmacovigilance centres and other sources such as specialized bulletins and journals, as well as partners in WHO. 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Table of Contents Regulatory Matters Atezolizumab ........................................................................................................ 4 Cetuximab (genetic recombination) ....................................................................... 4 COVID-19 vaccine NRVV Ad (ChAdOx1 nCoV-19) ................................................ 4 COVID-19 vaccine NRVV Ad26 (JNJ 78436735) ................................................... 4 Durvalumab (genetic recombination) ..................................................................... 5 Iopamidol .............................................................................................................. 5 Levothyroxine (tablet) ............................................................................................ 5 Nivolumab ............................................................................................................. 5 Obeticholic acid ..................................................................................................... 6 Polyethylene glycol (PEG) laxatives and starch-based thickeners ......................... 6 Pomalidomide, thalidomide ................................................................................... 6 Ritodrine and Magnesium sulfate (co-administration) ............................................ 7 Shosaikotokakikyosekko ....................................................................................... 7 Tozinameran ......................................................................................................... 7 Vascular endothelial growth factor (VEGF) inhibitors (systemic use) ..................... 7 Safety of medicines Amitriptyline .......................................................................................................... 9 Bendamustine ....................................................................................................... 9 Clonidine ............................................................................................................... 9 Clopidogrel ............................................................................................................ 9 Donepezil ............................................................................................................ 10 Fluoroquinolones ................................................................................................ 10 Indapamide ......................................................................................................... 10 Lamotrigine ......................................................................................................... 11 Nivolumab ........................................................................................................... 11 Theophylline ....................................................................................................... 11 Tozinameran, COVID-19 vaccine mRNA (mRNA 1273) ....................................... 11 Signal Levetiracetam and Hypokalaemia ........................................................................ 12 Remdesivir and pancreatic toxicity ...................................................................... 16 Tocilizumab and Pancreatitis ............................................................................... 22 WHO Pharmaceuticals Newsletter No. 3, 2021 3 Regulatory Matters Atezolizumab reported in patients treated (www.ema.europa.eu) with cetuximab in Japan in the (See also WHO Pharmaceuticals Newsletter Risk of severe cutaneous past three years, including No.2, 2021: Possible link to very rare cases adverse reactions (SCAR) three cases for which a causal of unusual blood clots with low blood relationship between the drug platelet counts in Europe) and event was assessed to be Malaysia. The National Pharmaceutical Regulatory reasonably possible. No patient Agency (NPRA) has announced mortalities have been reported. WHO, Global Advisory Committee on Vaccine Safety that the product information The MHLW and the PMDA (GACVS) review of latest for atezolizumab (Tecentriq®) concluded that the revision of evidence of rare adverse blood has been updated to include the package insert was coagulation events with the risk of severe cutaneous necessary. adverse reactions (SCAR). AstraZeneca COVID-19 Vaccine Reference: (Vaxzevria and Covishield), 16 Atezolizumab is indicated to Revision of Precautions, April 2021. treat non-small cell lung MHLW/PMDA, 30 March 2021 (https://www.who.int/news/item/16- cancer, small cell lung cancer (www.pmda.go.jp/english/) 04-2021-global-advisory-committee- and triple-negative breast on-vaccine-safety-(gacvs)-review- cancer. SCARs include acute of-latest-evidence-of-rare-adverse- generalized exanthematous blood-coagulation-events-with- pustulosis (AGEP), Stevens- astrazeneca-covid-19-vaccine- Johnson syndrome (JSJ), toxic COVID-19 vaccine (vaxzevria-and-covishield)) epidermal necrolysis (TEN) and drug rash with eosinophilia and NRVV Ad (ChAdOx1 systemic symptoms (DRESS). nCoV-19) Based on analysis from the COVID-19 vaccine company’s global safety data Risk of thrombosis with 99 cases of SCARs