Post-marketing safety of antineoplasic monoclonal antibodies: rituximab and trastuzumab.
OBJECTIVE
The aim of this study was to analyse the suspected adverse reactions associated with rituximab or trastuzumab reported to the Spanish Pharmacovigilance System.


METHODS
From this national database, we selected the spontaneous reports registered between 1 January 1999 and 1 June 2006 and analysed both age and gender of the patient, the dose prescribed, the severity of the report, the evolution, the latency and recovery periods of the adverse reaction, the reporting odds ratio (ROR) and the presence of other suspected drugs.


RESULTS
From 49 927 records registered in the period of analysis, 69 were associated with rituximab and 23 with trastuzumab. White cell disorders (n = 18), hypotension (n = 7), dyspnoea (n = 6) and pneumonitis (n = 4) were the most common adverse reactions associated with rituximab. The mean latency period of white cell disorders was 20.9 +/- 7.8 days, except in two cases where it was clearly longer (87 +/- 13 days). Hypotension and dyspnoea appeared immediately or a few days after the administration of the drug, and rapidly resolved. Pneumonitis seems to be a delayed adverse reaction, which required on average, 3 months to develop. Cardiac failure was the adverse reaction more frequently associated with trastuzumab (n = 7). In five of the seven cases of cardiac failure reported patients had been taking other suspected medications.


CONCLUSIONS
Our results are consistent with the safety profile of rituximab and trastuzumab observed in large randomised clinical trials.
González
V
V
Centro de Farmacovigilancia de Asturias, Facultad de Medicina, Universidad de Oviedo, Spain.
Salgueiro
E
E
Jimeno
F J
FJ
Hidalgo
A
A
Rubio
T
T
Manso
G
G
D016907:Adverse Drug Reaction Reporting Systems; D000911:Antibodies, Monoclonal / Q000009:adverse effects*; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents / Q000009:adverse effects*; D016208:Databases, Factual; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D000069283:Rituximab; D012720:Severity of Illness Index; D013030:Spain / Q000453:epidemiology; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D058846:Antibodies, Monoclonal, Murine-Derived; D000970:Antineoplastic Agents; D000069283:Rituximab; D000068878:Trastuzumab