PHARMACOEPIDEMIOLOGY AND DRUG SAFETY, VOL. zyxwv 5: 295-302 (1996) ORIGINAL REPORT Large Scale Safety Study of Ketoprofen zy 25 mg (Toprec@)in Febrile and Painful Conditions NICHOLAS MOORE', NICOLE VUILLEMIN*, MICHEL ABITEBOUL3, ODILE BOUDIGNAF, ANDRE PALIWODA', JEAN-LOUIS ROBIN' AND LAURENT-DIDIER JACOBS3 zyxw 'Service de Pharmaco/ogie. CHU de Rouen. 76031 Rouen Cedex, France; Hopital zyxw Louis Pasteur. Colmar, France; Rhdne-Poulenc-Rorer, Antony, France: 4Laboratoires Bellon. Neuilly. France; SITEM. Le Kremlin-Bicgtre, France SUMMARY zyxwv Objective zyxwvutsrq - To assess the safety, tolerability and efficacy of low-dose ketoprofen (75-150 mg daily for 5 to 15 days) in a general practice setting. Design - Open label, non-controlled study of ketoprofen 25 mg tablets in the treatment of pain in ENT diseases, dysmenorrhoea, and musculoskeletal disorders. Setting - General practice, 600 investigators Subjects - Four thousand and sixty-eight patients, aged 13-93 years, mean 42.3 years, 1009 with ENT diseases (mean age 38.8 (13-83) years, zyxwvu 53% female), 978 with dysmenorrhoea (mean age 30.3 (13-60) years, 100% female), 2081 with musculoskeletal disorders (mean age 49.6 (16-93) years, 54% female). Main outcome measures - Occurrence of adverse events, on patient and physician evaluation; dose and duration of treatment prescribed/taken (diary); global evaluation of efficacy by patient and physician. Result - Twenty-two patients were lost to follow-up (< l ? ' ~ ) ; dose effectively taken was lower than prescribed (3.3 versus 3.6 tablets/day); treatment was stopped prematurely in 3.3% of patients because of adverse events, in 17.1 YO because of early success of therapy. Gastrointestinal adverse events (AE) were the most frequent (76%) of AE), occurring in 10% of patients. They were more frequent in patients with musculoskeletal pain, who were older and had more associated diseases. Five patients were hospitalized, two for preplanned hospitalizations, the others for one asthma attack, one worsening of low back pain, and one angina attack, none attributed to treatment by the GP. None of the AE was life-threatening. Identified risk factors for AE were age and previous medical history, especially of gastrointestinal disorders. Conclusions - Good quality large scale studies with little or no loss to follow-up can be done in a general practice setting. At the dose used, ketoprofen was generally well tolerated, and used at a lower dose than prescribed, it was not associated with severe or new side-effects.The results of this study could justify its use in self-medication in these indications. KEY WORDS - ketoprofen; postmarketing cohort study; NSAIDS; analgesics; risk factors; adverse events INTRODUCTION Low doses of NSAIDs have shown consistent analgesic activity with little anti-inflammatory activity, and less risk of severe ~ide-effects,'-~ justifying the self-medication use of some of them. Ketoprofen is a propionic acid derivative non- steroidal anti-inflammatory drug (NSAID), widely Addressee for correspondence: N. Moore. used in many countries in rheumatic and non- rheumatic conditions, since 1973. Its usual anti- inflammatory dose is from 150 to 300 mg/day, and its usual side-effects are those of all NSAIDs, i.e. predominantly gastrointestinal dis- orders including GI bleeding, renal failure, and a risk of asthma exacerbation. Topre@ is a new 25 mg dosage form of ketoprofen, which has, at an average daily dose of 75 mg to 150 mg, essentially analgesic and CCC 1053-8569/96/050295-08 zyxwvut 0 1996 by John Wiley & Sons, Ltd. Received 16 December 1994 Accepted 16 March 1996