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Ibuprofen

Classification: A

Drug products: Alindrin®, Ardinex®, Brufen Retard, Brufen®, Burana, Burana Comp, Burana®, Ibumax, Ibumetin, Ibumetin®, Ibuprofen ABECE, Ibuprofen Actavis, Ibuprofen Apofri, Ibuprofen B. Braun, Ibuprofen Orifarm, Ibuprofen Orion, Ibuprofen ratiopharm, Ibuzin, Ifenin, Ipren, Ipren®, Iprensa, Neoprofen, Nurofen Apelsin, Nurofen Junior, Pedea®

ATC code: C01EB, C01EB16, M01AE01, M02AA13, N02AJ08

Substances: ibuprofen, ibuprofen arginate, ibuprofen D,L-lysine, ibuprofen DC 85, ibuprofen sodium dihydrate

Summary

Ibuprofen provide pain relief in both men and women. However, studies have shown conflicting results on the effect of ibuprofen in men and women. A meta-analysis of dental pain showed no differences in the effect between men and women. Some small studies have shown a better pain relief in men/boys.
A large epidemiologic pain study of many analgesics has shown that women have more side effects.
The risk of NSAID-induced liver affection was in a small case-control study larger in women, but a large cohort study did not find any differences in risk between men and women.
A large retrospective study shows a higher risk of gastric bleedings in all NSAID-treated patients, with a higher risk elevation in men.

Additional information

Pharmacokinetics and dosing

The effect of patient's sex on the pharmacokinetics after a single dose 600 mg ibuprofen was evaluated in healthy volunteers (18 men, 19 women). Patient's sex did not influence peak plasma concentration or the extent of binding to plasma protein. However, half-life was shorter and oral clearance was higher in young men compared to elderly men and women of all studied ages [6]. No influence of oral contraceptives on ibuprofen pharmacokinetics has been shown [7]. No sex differentiation in dosing has been recommended by the pharmaceutical company [8].

Effects

A meta-analysis evaluated the effect of patient’s sex on ibuprofen 400 mg in men and non-pregnant women with moderate to severe dental pain (119 men, 195 women, 15-35 years of age). No sex differences in analgesic response to ibuprofen were found [9]. A small study investigated the analgesic efficacy of ibuprofen 600 mg on postoperative endodontic pain (8 men, 7 women). There were no differences in pain reduction between men or women in the ibuprofen and placebo group [10]. However, in a small randomized, double-blind, placebo-controlled trial examining the ability of ibuprofen to reduced experimental (voltage induced C-fiber nociceptive activation) pain in healthy young pain-free subjects (10 men, 10 women, 18-30 years of age), analgesic effect of ibuprofen 800 mg was found only in men [11].

A more recent study (10 men, 10 women) analysed sex differences in ibuprofen and placebo analgesia expectancy. In men, both placebo and ibuprofen analgesia were dependent upon expectancy; when they were told they were receiving ibuprofen, they had an analgesic response, even if receiving placebo. In women, ibuprofen was ineffective in producing analgesia regardless of their expectations [12].

Pain relief in children with migraine was examined in a randomized, double-blind, placebo-controlled study (49 boys, 35 girls, age 6-12 years). They were given ibuprofen 7.5 mg/kg or placebo. Boys taking ibuprofen responded effectively while girls did not. No analysis of pharmacokinetics variables was performed [13].

Adverse effects

The PAIN study (3611 men, 5009 women) was a large randomized double-blind trial of the tolerability of paracetamol, aspirin and ibuprofen. Analysis of potential risk factors for adverse events among patients in the PAIN study shows that female sex is one risk factor [14].A nested control study 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 diclofenac was 2.2 compared to 4.0 for naproxen, and 1.6 for ibuprofen [1].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].A cross-sectional study (19 756 men, 18 640 women) investigated the relationship between use of aspirin or ibuprofen and risk of colorectal polyp prevalence. A trend for dose-dependent risk reductions were seen in men using aspirin or ibuprofen > 2 times/day. A trend for protective effects in women were only found among those with BMI <25 and a regular use of aspirin or ibuprofen [15].

Reproductive health issues

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

Updated: 2019-05-27

Date of litterature search: 2014-10-14

References

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  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. Johnson CC, Hayes RB, Schoen RE, Gunter MJ, Huang WY, PLCO Trial Team. Non-steroidal anti-inflammatory drug use and colorectal polyps in the Prostate, Lung, Colorectal, And Ovarian Cancer Screening Trial. Am J Gastroenterol. 2010;105:2646-55. PubMed
  7. Greenblatt DJ, Abernethy DR, Matlis R, Harmatz JS, Shader RI. Absorption and disposition of ibuprofen in the elderly. Arthritis Rheum. 1984;27:1066-9. PubMed
  8. Knights KM, McLean CF, Tonkin AL, Miners JO. Lack of effect of gender and oral contraceptive steroids on the pharmacokinetics of (R)-ibuprofen in humans. Br J Clin Pharmacol. 1995;40:153-6. PubMed
  9. Brufen (ibuprofen). Summary of Products Characteristics. Medical Products Agency - Sweden; 2016.
  10. Averbuch M, Katzper M. A search for sex differences in response to analgesia. Arch Intern Med. 2000;160:3424-8. PubMed
  11. Ryan JL, Jureidini B, Hodges JS, Baisden M, Swift JQ, Bowles WR. Gender differences in analgesia for endodontic pain. J Endod. 2008;34:552-6. PubMed
  12. Walker JS, Carmody JJ. Experimental pain in healthy human subjects: gender differences in nociception and in response to ibuprofen. Anesth Analg. 1998;86:1257-62. PubMed
  13. Butcher BE, Carmody JJ. Sex differences in analgesic response to ibuprofen are influenced by expectancy: a randomized, crossover, balanced placebo-designed study. Eur J Pain. 2012;16:1005-13. PubMed
  14. Lewis DW, Kellstein D, Dahl G, Burke B, Frank LM, Toor S et al. Children's ibuprofen suspension for the acute treatment of pediatric migraine. Headache. 2002;42:780-6. PubMed
  15. Moore N, Charlesworth A, Van Ganse E, LeParc JM, Jones JK, Wall R et al. Risk factors for adverse events in analgesic drug users: results from the PAIN study. Pharmacoepidemiol Drug Saf. 2003;12:601-10. PubMed
  16. Concise (INSIKT). Kalmar: eHälsomyndigheten. 2018 [cited 2019-03-14.] länk

Authors: Linnéa Karlsson Lind

Reviewed by: Mia von Euler

Approved by: Karin Schenck-Gustafsson