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Ketoprofen

Klassificering: A

Preparat: Ketoflex, Ketoprofen Mylan, Ketoprofen Retard Mylan, Ketospray, Orudis, Orudis Retard, Orudis®, Orudis® Retard, Prodon®, Profenid, Siduro®, Siduro® Retard, Zon

ATC kod: M01AE03, M02AA10

Substanser: ketoprofen

Sammanfattning

Risken för NSAID-inducerad leverskada var högre hos kvinnor i en liten fall-kontrollstudie, medan en stor kohortstudie inte visade någon könsskillnad.
En stor retrospektiv studie fann högre risk för magblödning för NSAID-behandlade patienter och riskökningen var större för män. En annan studie på patienter med ketoprofenbehandling vid reumatoid artrit visade dock större risk för magblödning hos kvinnor.
 
Kunskapsunderlaget avseende skillnader mellan kvinnor och män är begränsat och motiverar inte olika dosering eller behandling.

Additional information

Pharmacokinetics and dosing

The pharmacokinetics of ketoprofen enantiomers were evaluated in healthy volunteers (12 men, 13 women) in an unblinded, randomized crossover study. Doses of 25, 50, or 100 mg of (R)-ketoprofen and 100 mg of racemic ketoprofen (R+S) (Orudis®) were administered orally on four separate occasions at least a week apart. Fractional inversion of (R)-ketoprofen was not different between men and women. Women had a higher elimination rate constant for (R)-ketoprofen after the racemate dose. Clearance did not differ between men and women. Thus, the clinical significance is unclear [1]. No sex differentiation in dosing has been recommended by the manufacturer [6].

Effects

The only study found regarding sex differences in the effect of ketoprofen was a small double-blind placebo-controlled clinical study (6 men, 11 women) on pain and inflammation in osteoarthritis. No differences between men and women were reported [7].

Adverse effects

The safety of ketoprofen was evaluated in a French multicenter study including patients suffering from painful rheumatic disorders and aged over 60 years (6748 men, 13029 women). Patients received 200 mg ketoprofen once daily for one month. A multivariate analysis showed that women had more adverse side effects, especially those related to the gastro-intestinal (GI) tract (men: 15.2%; women: 18.4%). However, the sex of the patient was not prognostic for GI adverse drug reactions [8]. This is contrary to the findings in a large nested control study, which estimated the risk of upper gastrointestinal complications associated with selective cox 2-inhibitors and non-selective NSAIDs compared with non-use of NSAIDs. In all > 600 000 individuals contributed to >1 million person-years of observation and 726 upper gastrointestinal complications were identified. Male sex and high age carried a higher risk of complication and suggested a synergistic effect between these factors and NSAIDs on the risk of upper gastrointestinal complications. The risk for upper gastrointestinal complications differed between the various NSAIDs. Adjusted for male sex and age, the OR for various NSAIDs including ketoprofen was 3.4, compared to 2.2 for diclofenac, 4.0 for naproxen, 1.6 for ibuprofen [9].A retrospective cohort study (625 307 patients with 2 130 820 prescriptions, one third of these were to men) found that incidence rates of NSAID-induced acute liver injury were similar for men and women and for the young and the elderly [2]. However, a case-control study (136 men, 130 women) found an association between NSAID exposure and liver injury in women but not in men (OR 6.49 vs. 1.06). This may be due to differences in pharmacokinetics or circulating level hormones and/or greater use of multiple medications in women [3] or to a generally higher risk of drug-induced liver injury in women [4].A meta-analysis evaluated NSAID use and the risk of Parkinson’s disease. Pooled risk ratio of Parkinson’s disease were similar in men and women using NSAID (men 0.79 (95%CI 0.69, 0.92); women 0.72 (95%CI 0.45, 1.15)) [5].

Reproductive health issues

Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).

Försäljning på recept

Fler kvinnor än män hämtade ut kapslar innehållande ketoprofen (ATC-kod M01AE03) på recept i Sverige år 2015, totalt 34 019 kvinnor och 18 693 män. Det motsvarar 7,0 respektive 3,8 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 50-74 år hos båda könen. Totalt sett var kapslar innehållande ketoprofen 1,8 gånger vanligare hos kvinnor [10].

Fler kvinnor än män hämtade ut gel innehållande ketoprofen (ATC-kod M02AA10) på recept i Sverige år 2015, totalt 20 420 kvinnor och 11 135 män. Det motsvarar 4,2 respektive 2,3 personer per tusen invånare. Andelen som hämtat ut läkemedel ökade med stigande ålder hos båda könen. I genomsnitt var gel innehållande ketoprofen 1,5 gånger vanligare hos kvinnor [10].

Uppdaterat: 2019-02-26

Litteratursökningsdatum: 2014-10-14

Referenser

  1. Rudy AC, Liu Y, Brater C, Hall SD. Stereoselective pharmacokinetics and inversion of (R)- ketoprofen in healthy volunteers. J Clin Pharmacol. 1998;38:3S-10S. PubMed
  2. García Rodríguez LA, Williams R, Derby LE, Dean AD, Jick H. Acute liver injury associated with nonsteroidal anti-inflammatory drugs and the role of risk factors. Arch Intern Med. 1994;154:311-6. PubMed
  3. Lacroix I, Soussan C, Portolan G, Montastruc JL. Drug-induced adverse reactions via breastfeeding: a study in the French Pharmacovigilance Database. Fundam Clin Pharmacol. 2013;27 (Suppl. 1):42-3. Abstract 26-01.
  4. Leise MD, Poterucha JJ, Talwalkar JA. Drug-induced liver injury. Mayo Clin Proc. 2014;89:95-106. PubMed
  5. Samii A, Etminan M, Wiens MO, Jafari S. NSAID use and the risk of Parkinson's disease: systematic review and meta-analysis of observational studies. Drugs Aging. 2009;26:769-79. PubMed
  6. Orudis (ketoprofen). Summary of Product Characteristics. Medical Products Agency - Sweden; 2016.
  7. Famaey JP, Colinet E. A double-blind trial of ketoprofen in the treatment of osteoarthritis of the hip. Rheumatol Rehabil. 1976;Suppl:45-9. PubMed
  8. Le Loet X. Safety of ketoprofen in the elderly: a prospective study on 20,000 patients. Scand J Rheumatol Suppl. 1989;83:21-7. PubMed
  9. Castellsague J, Holick CN, Hoffman CC, Gimeno V, Stang MR, Perez-Gutthann S. Risk of upper gastrointestinal complications associated with cyclooxygenase-2 selective and nonselective nonsteroidal antiinflammatory drugs. Pharmacotherapy. 2009;29:1397-407. PubMed
  10. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-05.] länk

Författare: Linnéa Karlsson Lind, Desirée Loikas

Faktagranskat av: Mia von Euler

Godkänt av: Karin Schenck-Gustafsson