Cutaneous adverse effects of ketoprofen for topical use: clinical patterns and costs.

BACKGROUND: Since its introduction in France, ketoprofen for topical use has been associated with a large number of cutaneous adverse effect reports. Therefore, the French Medicine Agency progressively introduced warnings and contraindications to its use. Despite this, serious adverse drug reactions (ADRs) still occur. OBJECTIVE: To describe clinical patterns and estimate costs of spontaneously reported cutaneous ADRs of topical ketoprofen. METHODS: All cases of cutaneous ADRs of topical ketoprofen reported to the Bordeaux regional pharmacovigilance center between January 1989 and December 2006 were included. Clinical patterns, in respect of adherence to recommendations, causality, seriousness, and direct costs incurred by the ADRs, were assessed. RESULTS: A total of 136 cases were reported (median age: 42 years, 55.9% women). Proper use of topical ketoprofen regarding indications, warnings, and contraindications was not respected by one-third of the patients. Almost all cases occurred during sunny months. Symptoms consisted predominantly of bullous eruptions (29.4%) or contact dermatitis (27.2%). Generalized lesions were observed in 37.5% of patients. Causality was considered at least possible for most of the cases (92.6%). These ADRs induced hospital admission in 15 cases (11.0%). The total estimated cost was euro 42,962 ($US 66,559), corresponding to euro 316 per case. This mean cost was nine times higher for serious ADRs. CONCLUSION: Topical ketoprofen is used to treat benign symptoms but can be associated with serious and costly cutaneous ADRs. Furthermore, the number of cases and the calculated costs may have been greatly under-estimated in the present study.

A randomized, controlled clinical trial of ketoprofen for sickle-cell disease vaso-occlusive crises in adults.

Vaso-occlusive crisis (VOC) is the primary cause of hospitalization of patients with sickle-cell disease. Treatment mainly consists of intravenous morphine, which has many dose-related side effects. Nonsteroidal antiinflammatory drugs have been proposed to provide pain relief and decrease the need for opioids. Nevertheless, only a few underpowered trials of nonsteroidal antiinflammatory drugs for sickle-cell VOC have been conducted, and conflicting results were reported. We conducted a phase 3, double-blind, randomized, placebo-controlled trial with ketoprofen (300 mg/day for 5 days), a nonselective cyclooxygenase inhibitor, for severe VOC in adults. A total of 66 VOC episodes were included. The primary efficacy outcome was VOC duration. The secondary end points were morphine consumption, pain relief, and treatment failure. Seven VOC episodes in each group were excluded from the analysis because of treatment failures. No significant between-group differences were observed for the primary outcome or the secondary end points. Thus, although ketoprofen was well-tolerated, it had no significant efficacy as treatment of VOC requiring hospitalization. These findings argue against its systematic use in this setting.

The economic consequences of NSAID-induced gastropathy: the French context.

The costs of treating gastroduodenal ulcers caused by nonsteroidal anti-inflammatory drugs (NSAIDs) are shown to increase the total cost of NSAID treatment to the Assurance-Maladie, the French national health insurance system. This increased cost is termed the iatrogenic cost factor, and is defined as the ratio of the shadow price of an NSAID to its reimbursed cost. The shadow price is calculated from estimates of the incidence of NSAID-induced gastropathies, the cost of the drug, and the hospital and ambulatory costs of treating the gastropathies. The resulting iatrogenic cost factors are estimated as 1.36 for naproxen, 1.48 for sulindac, 1.65 for diclofenac, 1.67 for piroxicam, 2.00 for ketoprofen, and 2.12 for etodolac.