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Reporting rate of adverse drug reactions to the French pharmacovigilance system with three step 2 analgesic drugs: dextropropoxyphene, tramadol and codeine (in combination with paracetamol)
Author(s) -
Tavassoli Neda,
LapeyreMestre Maryse,
Sommet Agnès,
Montastruc JeanLouis
Publication year - 2009
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2009.03472.x
Subject(s) - propoxyphene , tramadol , codeine , analgesic , pharmacovigilance , medicine , pharmacology , drug , anesthesia , morphine
WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Three ‘weak’ opioid analgesics are marketed in France and other European countries in association with paracetamol. • They are very largely used, but to our knowledge there is no large study comparing the reporting rate of adverse drug reactions (ADRs) between these different step 2 analgesic combinations to determine the safest one. WHAT THIS STUDY ADDS • The aim of this study was to compare reporting rate of ADRs with three step 2 combinations according to their consumption in France. • The results show that among these combinations, reporting rate and ‘seriousness’ of reported ADRs are the highest with tramadol/paracetamol (TRM+P) and the lowest with codeine/paracetamol. • The safety of TRM+P needs to be urgently investigated with more methodologically rigorous studies. AIMS Three ‘weak’ opioid analgesics in association with paracetamol are marketed in France as step 2 analgesics: dextropropoxyphene, tramadol and codeine. These combinations are involved in several adverse drug reactions (ADRs), but no data are available about their comparative reporting rate. The aim was to compare the reporting rate of ADRs between tramadol/paracetamol (TRM+P), codeine/paracetamol (COD+P) and dextropropoxyphene/paracetamol (DXP+P). METHODS All spontaneous reports submitted to the French Pharmacovigilance Database from 1 January 1987 to 31 December 2006 suspected to be induced by one of the three step 2 analgesic combinations (DXP+P, TRM+P, COD+P) were extracted. Their consumption for the same period was obtained from the French Drug Agency. The number of ADRs, serious ADRs and different organ classes of ADRs were compared according to their consumption. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were calculated for each variable using DXP+P as reference. RESULTS The reporting rate of ADRs was calculated as 24.9/100 000 person‐years for DXP+P, 44.5/100 000 person‐years for TRM+P and 12.5/100 000 person‐years for COD+P. The reporting rate (OR 0.56, 95% CI 0.50, 0.63) and ‘seriousness»’ (OR 0.65, 95% CI 0.53, 0.80) of ADRs were significantly higher with TRM+P than with DXP+P. However, hepatobiliary ADRs were significantly more frequent with the DXP+P combination (OR 2.62, 95% CI 1.59, 4.37). In contrast, the reporting rate (OR 1.99, 95% CI 1.82, 2.18) and ‘seriousness’ (OR 2.64, 95% CI 2.24, 3.11) of ADRs were significantly higher with DXP+P than with COD+P. CONCLUSIONS Among the three step 2 analgesic combinations, reporting rate and ‘seriousness’ of ADRs are the highest with TRM+P and the lowest with COD+P. Our study suggests that the safety profile of DXP+P is worst than that of COD+P.