Table 4.
Characteristics of studies of the occurrence of ADRs related to NSAID use
| Reference | Setting | Medicines | ADRs | Sampling period | Sample size | Outcome measures |
Results (95%CI) |
Type of ADRs |
|
Case control studies |
||||||||
| Hernandez-Diaz 2001[37] | UK | NSAIDs | Gastrointestinal events | 1993–1998 | 2,105 cases/ 11,500 controls |
OR | 1.8; 1.3 – 2.4. | A |
| Mockenhaupt 2003 [38] | DE/US | NSAIDs | Steven-Johnson syndrome | 1989–1995 | 245 cases/ 1147 controls |
PRR | 34, 95; 11–105 | B |
| Lacroix 2004 [39] | FR | NSAIDs | Liver injury | 1998–2000 | 88 cases/ 178 controls |
OR | Women: 6.49; 1.67–25.16 Men: 1.06; 0.36–3.12 |
B |
| Cohort studies | ||||||||
| Lipworth 2004 [40] | DK | Ibuprofen | Mortality | 1989–1995 | 113,538 patients |
SMR (standard mortality rate) | 1.21; 1.19–1.24 | A/B |
| Ashworth 2004 [41] | CA | Diclofenac Naproxen Arthrotec |
Mortality | 1991–1994 | 18,424 patients | OR | Arthrotec: 1.4; 0.9–2.1. Diclofenac: 2.0; 1.3–3.1. Naproxen: 3.0; 1.9–4.6 |
A/B |
| Morant 2004 [42] | UK | NSAIDs | Gastrointestinal haemorrhage | 1987–2001 | 628000 patient year | PRR | 0.84; 0.60 – 1.17 | A |
| Martin 2000 [43] | UK | Meloxicam | Gastrointestinal events | 1996–1997 | 19,087 patients | Events/ 1000 patient-months of exposure |
Dyspepsia: 28.3 Gastrointestinal haemorrhage: 0.4 |
A + B |
| National ADR databases | ||||||||
| Lugardon 2004 [44] | FR | COX-2 inhibitors | Oeso-gastro-duodenal events: | 2000–2002 | 505 cases/ 2,525 non-cases |
OR | 14.9; 9.3–23.7 | A |
| Durrieu 2005 [45] | FR | COX-2 inhibitors | Arterial hypertension | 2000–2003 | 34 cases | OR | 3.3; 1.6–6.9. | A |
| Clinard 2004 [46] | FR | NSAIDs | Excess risk of adverse drug reactions | 1995–1999 | 3983 cases/ 54,583 non- cases |
OR | Different categories reported | B |
| Brinker 2004 [47] | US | COX-2 inhibitors | Hypertension | < 2002 | 34 cases | Reporting rate/106person years | Rofecoxib: 5.0 Celecoxib: 1.3 |
A |
| La Grenade 2005 [48] | US | COX-2 inhibitors Meloxicam |
Steven-Johnson syndrome Toxic Epidermal Necrolysis |
< 2004 | 123 cases | Reporting rate/106person years | Valdecoxib: 49 Celecoxib: 6 Rofecoxib: 3 |
B |
| Polimeni 2006 [49] | Sicilian | NSAIDs | All | 1998–2002 | 1585 cases | PRR | Hepatitis: 14.20 Vasculitis: 7.72 Hypertension: 15.40 |
B |
| Conforti 2001 [50] | IT | NSAIDs | Gastrointestinal events | 1996–1999 | 705 cases/ 10,608 non cases |
% ADRs | Nimesulid: 10.4 Diclofenac: 21.2 Ketoprofen: 1.7 Piroxicam: 18.6 |
A |
| Ahmad 2002 [51] | US | COX-2 inhibitors | Renal failure | 1969–2000 | Celecoxib: 122 cases Rofecoxib: 142 cases |
Case review | Case review | A |
| Puijenbroek 2000 [52] | NL | NSAIDs Diuretics |
Drug interactions | 1990–1999 | 305 cases/ 9517 non cases |
OR | OR: 2.0, 1.1–3.7 | D |
| Lapeyre-Mestre 2004 [53] | FR/ES | NSAIDs | Hepatic events | 1982–2001 | 29,486 cases | OR | Different OR calculated for NSAIDs. | B |
| Leone 1999 [54] | IT | Nimesulide | Renal impairment | 1988–1997 | 11cases/ 7438 non cases |
Causality assessment | Possible (n = 6) Probable (n = 4) Certain (n = 1) |
A |
| Brown 1998 [55] | UK | Tiaprofenic acid | Cystitis | 1981–1996 | 221 cases/ 1327 non cases |
ADRs/105 prescriptions | 1991: 4.2 1992: 5.9 1993: 4.2 1994: 34.4 1995: 18.5 1996: 6.5 |
B |
| Verrico 2003 [56] | US | COX2-inhibitors | Not specified | 1999–2002 | 24 cases | Causality assessment | Possible (n = 29) Probable (n = 16) |
A |
| Kahn 1997 [57] | US | NSAIDs | Necrotizing soft tissue infections | 1969–1995 | 33 cases | Case review | N = 26 | C |
| PEM | ||||||||
| Layton 2004a [58] | UK | Celecoxib | Not specified | 2000 | 17,458 patients | IDs (event incidence densitites) | Dyspepsia = 25.4 Abdominal pain = 10.6 |
A + B |
| Layton 2003b [59] | UK | Celecoxib Meloxicam |
Not specified | 1996–1997 | 34,355 patients | PRR | Different categories reported | A |
| Layton 2003c [60] | UK | Rofecoxib | Not specified | 2000 | 15,268 patients | Event rate pr. 1000 patient months exposure | 76 upper GI bleedings and 101 thromboembolic events | A + B |
| Layton 2004d [61] | UK | Rofecoxib | Exacerbation of colitis | 1999 | 15,268 patients | IRR | 5.8; 2.7–11.3 | A |
| Kasliwal 2005 [62] | UK | COX-2 inhibitors | Gastrointestinal + thromboembolic events |
1999–2000 | 32,726 patients | PRR | GI: 1.21; 1.09 – 1.36. Thromboembolic: 1.04; 0.50 – 2.17. |
A + B |
| Layton 2003e [63] | UK | Rofecoxib Meloxicam |
Thromboembolic events | 1996–1997 | 34,355 patients | PRR | 1.68; 1.15 – 2.46. | A |
| Layton 2003f [64] | UK | Rofecoxib Meloxicam |
Upper GI events | 1996–1997 | 34,355 patients | IR | 0.71; 0.65 – 0.79. | A |
| Layton 2006g [65] | UK | COX-2 inhibitors | Serious skin reactions | 1999–2000/ | 52,644 patients | IR/1000 patient-months | IR: 0.019 | B |
| Layton 2003h [66] | UK | Celecoxib Meloxicam |
Gastrointestinal events | 1996–1997 | 36,545 patients | PRR | 0.77; 0.69 – 0.85. | A |
| Case series | ||||||||
| Onder 2004 [67] | - | NSAIDs | Psychiatric ADRs | 1965–2003 | 27 reports with data on 453 cases | Risk factors | Age, psychiatric disorders, parturients | B |
| Fraunfelder 2006 [68] | - | NSAIDs | Ocular ADRs | - | 569 cases | Reported ADRs | Blurred vision, conjunctivitis, visual hallucinations | B |
| Zimer 2007 [69] | DE | Valdecoxib | Cutaneous adverse reactions | 2002–2005 | 5 cases | Case review | Erythematous, facial edema, dyspnea | B |
| Case reports | ||||||||
| Hunter 1999 [70] | - | Bromfenac | Hepatic Failure | - | 1 case | Causality assessment | Related | B |
| ADRAC 1998 [71] | - | Diclofenac Indomethacin Mefenamic acid |
Closure of fetal ductus arterious | - | 3 cases | Case review | Case review | C |