Table 3.
Safety concerns involved in post-authorisation amendments to aRMMs
| Type of amendment | Product concerned | Safety concern description | Source of evidence | Follow-up time (months) |
|---|---|---|---|---|
| Introduction | ATryn©, Laboratoire Francais du Fractionnement et des Biotechnologies, France (antithrombin alfa) | Off-label use | Spontaneous reports | 137 |
| Rotarix©, GlaxoSmithKline Biologicals S.A., Belgium (human rotavirus, live attenuated) | Administration error (accidental parenteral instead of oral) | Spontaneous reports | 63 | |
| Cubicin©, Merck Sharp & Dohme B.V., The Netherlands (daptomycin) | Skeletal muscle toxicity |
Clinical trials Non-clinical studies |
118 | |
| Reduced susceptibility in Staphylococcus aureus | ||||
| Optimark©, Mallinckrodt Deutschland GmbH, France (gadoversetamide) | Nephrogenic systemic fibrosis |
Clinical trials Non-clinical studies Spontaneous reports |
37 | |
| Vectibix©, Amgen Europe B.V., The Netherlands (panitumumab) | Lack of response and negative effects in combination with oxaliplatin-based chemotherapy in patients with mutant KRAS tumours | Clinical trials | 40 | |
| Evicel©, Omrix Biopharmaceuticals N.V., Belgium (human fibrinogen/human thrombin) | Air or gas embolism | Spontaneous reports | 23 | |
| Effentora©, Teva B.V., The Netherlands (fentanyl) | Misuse, abuse and diversion | Spontaneous reports | 21 | |
| Use in patients who are not already receiving maintenance opioid therapy | ||||
| Unintended (accidental) exposure | ||||
| Pandemrix©, GlaxoSmithKline Biologicals S.A., Belgium [split influenza virus inactivated, containing antigen equivalent to A/California/07/2009 (H1N1)-derived strain used NYMC X-179A] | Medical errors/misidentification of vaccine | Spontaneous reports | 17 | |
| Coring of the rubber stopper on the antigen vial | ||||
| Contamination of multiple-dose vials | ||||
| Pradaxa©, Boehringer Ingelheim International GmbH, Germany (dabigatran etexilate mesilate) | Haemorrhage | Clinical trials | 74 | |
| Vpriv©, Shire Pharmaceuticals Ireland Ltd, Ireland (velaglucerase alfa) | Infusion-related reactions | Observational studies | 71 | |
| Prolia©, Amgen Europe B.V., The Netherlands (denosumab) | Osteonecrosis of the jaw |
Clinical trials Observational studies Spontaneous reports |
60 | |
| Eliquis©, Bristol-Myers Squibb/Pfizer EEIG, Ireland (apixaban) | Bleeding | Clinical trials | 17 | |
| Severe renal or hepatic impairment | ||||
| Liver injury | ||||
| Xgeva©, Amgen Europe B.V., The Netherlands (denosumab) | Osteonecrosis of the jaw |
Clinical trials Observational studies Spontaneous reports |
46 | |
| Rienso©, Takeda Pharma A/S, Denmark (ferumoxytol) | Hypersensitivity | Spontaneous reports | 26 | |
| Discontinuation | Hirobriz Breezhaler©, Novartis Europharm Limited, Ireland (indacaterol maleate) | Off-label use | Observational studies | 93 |
| Renvela©, Genzyme Europe BV, The Netherlands (sevelamer carbonate) | Arteriovenous fistula site adverse drug reactions | Unknown | 96 | |
| Peritonitis | ||||
| Vitamin deficiency | ||||
| Revolade©, Novartis Europharm Limited, Ireland (eltrombopag olamine) | Hepatotoxicity | Unknown, considered part of clinical practice | 87 | |
| Thromboembolic events | ||||
| Post therapy reoccurrence of thrombocytopenia | ||||
| Potential for increase in bone marrow reticulin formation | ||||
| Haematological malignancies | ||||
| HyQvia©, Baxalta Innovations GmbH, Austria (human normal immunoglobulin) | Safety in pregnant and lactating women | Non-clinical studies | 25 |
aRMMs additional risk minimisation measures