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Oxycodone

Classification: A

Drug products: Lindoxa, Oxikodon Actavis, Oxikodon Depot Acino, Oxikodon Depot Actavis, Oxikodon Depot Evolan, Oxycodon Ratiopharm, Oxycodone Depot 1A Farma, Oxycodone Depot Lannacher, Oxycodone Depot Orion, Oxycodone Depot Teva, Oxycodone G.L., Oxycodone Hameln, Oxycodone Orion, Oxycodone Teva, Oxycodone Vitabalans, Oxyconta Depot, OxyContin®, Oxydorine Depot, OxyNorm®

ATC code: N02AA05

Substances: oxycodone, oxycodone hydrochloride

Summary

Published controlled studies on differences between men and women in effect of oxycodone are lacking.

Pharmacokinetic studies show conflicting results.
Retrospective studies on the analgetic effect of oxycodone has shown that men receive higher doses than women.
 
The present evidence concerning differences between men and women is limited and do not motivate differentiation in dosing or treatment.

Additional information

The scientific literature indicates that pain behavior and pain perception may vary between men and women. This could be influenced by differences in pharmacokinetics, sex hormones, differences in stress response, or type of pain test. Also, many variables other than a person’s sex/gender account for individual differences in pain sensitivity. The prevalence of several clinical pain conditions is higher in women than in men, which suggests that either different clinical pain mechanisms may operate in men vs. women, or different or additional risk factors are relevant in one sex, or a combination of differences [1]. Therefore, sex differences of pain releasing medication might thus be difficult to interpret [2].

Pharmacokinetics and dosing

Studies on sex differences in oxycodone pharmacokinetics show contradictory results. A pharmacokinetic study (247 men, 192 women) showed that male cancer patients had about 30% higher serum concentrations of oxycodone than female patients but the doses in men were higher (80 mg/day vs. 70 mg/day). It is suggested that the higher body weight of men can’t account for this differences since dosing for cancer pain is not based on weight. A possible explanation may be that men are less sensitive to opioids and therefore require higher doses to relieve similar levels of pain [3].

Women had higher levels of the active metabolite oxymorphone and the inactive metabolites noroxymorphone, and noroxycodone but lower concentrations of the parent substance oxycodone than men. Similar findings have been observed in another study [4]. The metabolism of oxycodone is primarily through CYP3A4, which activity is higher in women [5]. Another study (14 men, 14 women) found no significant differences in mean oxycodone AUC and Cmax between men and women after a single 20 mg oral oxycodone dose. When adjusting for bodyweight, women eliminated oxycodone 25% more slowly than men. However, women had lower mean AUC and Cmax of the active metabolite oxymorphone. This suggests that the metabolism of oxycodone to oxymorphone is based on sex [6].

Despite the pharmacokinetic differences of oxycodone, the clinical studies have shown effect with similar doses in men and women and no sex differentiation in dosing has been suggested [7].Factors influencing of opioid doses prescribed to cancer patients have been analyzed retrospectively according to pharmacy records in North America (3631 men, 3570 women). Patients received sustained-release morphine, sustained-release oxycodone, or transdermal fentanyl. Sustained-release doses were converted to OME (oral morphine equivalent). The mean opioid dose was 142.4 mg/day for women and 157.4 mg/day for men. However, when controlling for age and primary tumor site, this differences was not significant [2].

Effects

The efficacy of oxycodone has been evaluated in an open-label study based on a questionnaire to young and elderly men and women (14 men, 14 women) receiving 20 mg oxycodone. Women had a greater feeling of drug effect than men [6].

Adverse effects

An observational study of elderly people (520 men, 827 women, mean age 73 years) has shown that postoperative nausea and vomiting are more common in women (+91%) [8]. Also, a study on postoperative oxycodone-induced nausea and emesis has shown this to be higher in women than in men [9]. If this is due to the medication was not explored in these studies.

In a randomized, double-blind, placebo-controlled trial, light drinkers (8 men, 7 women) and moderate drinkers (8 men, 6 women) received 0, 10 and 20 mg of oral oxycodone. Women treated with 20 mg oxycodone reported more frequent and pronounced adverse effects (dizziness, nausea, vomiting etc.) than men. A suggested explanation was that oxycodone was not adjusted for body weight, and since men weighed more than women in this study, women got higher doses than men [10].

Reproductive health issues

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

Updated: 2020-08-28

Date of litterature search: 2015-01-30

References

  1. Greenspan JD, Craft RM, LeResche L, Arendt-Nielsen L, Berkley KJ, Fillingim RB et al. Studying sex and gender differences in pain and analgesia: a consensus report. Pain. 2007;132 Suppl 1:S26-45. PubMed
  2. Dance A. Why the sexes don't feel pain the same way. Nature. 2019;567(7749):448-450. PubMed
  3. Hall S, Gallagher RM, Gracely E, Knowlton C, Wescules D. The terminal cancer patient: effects of age, gender, and primary tumor site on opioid dose. Pain Med. 2003;4:125-34. PubMed
  4. Andreassen TN, Klepstad P, Davies A, Bjordal K, Lundström S, Kaasa S et al. Influences on the pharmacokinetics of oxycodone: a multicentre cross-sectional study in 439 adult cancer patients. Eur J Clin Pharmacol. 2011;67:493-506. PubMed
  5. Elder NM, Atayee RS, Best BM, Ma JD. Observations of urinary oxycodone and metabolite distributions in pain patients. J Anal Toxicol. 2014;38:129-34. PubMed
  6. Harris RZ, Benet LZ, Schwartz JB. Gender effects in pharmacokinetics and pharmacodynamics. Drugs. 1995;50:222-39. PubMed
  7. Kaiko RF, Benziger DP, Fitzmartin RD, Burke BE, Reder RF, Goldenheim PD. Pharmacokinetic-pharmacodynamic relationships of controlled-release oxycodone. Clin Pharmacol Ther. 1996;59:52-61. PubMed
  8. OxyNorm (oxycodone). Summary of Product Characteristics. Medical Products Agency Sweden; 2016.
  9. Conti D, Ballo P, Boccalini R, Boccherini A, Cantini S, Venni A et al. The effect of patient sex on the incidence of early adverse effects in a population of elderly patients. Anaesth Intensive Care. 2014;42:455-9. PubMed
  10. Koivuranta M, Läärä E, Snåre L, Alahuhta S. A survey of postoperative nausea and vomiting. Anaesthesia. 1997;52:443-9. PubMed
  11. Zacny JP, Drum M. Psychopharmacological effects of oxycodone in healthy volunteers: roles of alcohol-drinking status and sex. Drug Alcohol Depend. 2010;107:209-14. PubMed
  12. Läkemedelsstatistik. Stockholm: Socialstyrelsen. 2015 [cited 2016-04-29] länk
  13. Wändell P, Carlsson AC, Wettermark B, Lord G, Cars T, Ljunggren G. Most common diseases diagnosed in primary care in Stockholm, Sweden, in 2011. Fam Pract. 2013;30:506-13. PubMed
  14. Shega JW, Tiedt AD, Grant K, Dale W. Pain measurement in the National Social Life, Health, and Aging Project: presence, intensity, and location. J Gerontol B Psychol Sci Soc Sci. 2014;69 Suppl 2:S191-7. PubMed

Authors: Linnéa Karlsson Lind, Desirée Loikas

Reviewed by: Mia von Euler

Approved by: Karin Schenck-Gustafsson