Oxycodone
Classification: AATC code: N02AA05
Summary
Published controlled studies on differences between men and women in effect of oxycodone are lacking. Women treated with oxycodone are twice as likely as men to have adverse effects. Pharmacokinetic studies show conflicting results. Retrospective studies on the analgetic effect of oxycodone in cancer pain have shown that men receive higher doses than women. The dose must be individualized in both men and women.
Additional information
The prevalence of several clinical pain conditions is higher in women than in men. Differences in pharmacokinetics, sex hormones, stress response, or socio-cultural aspects may be of importance [1-3]. Therefore, sex and gender differences of pain medications are difficult to interpret [4].Studies on abuse potential of opioids have not been included in this document.
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 difference 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 [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 body weight, women eliminated oxycodone 25% more slowly than men [6].Studies indicate small sex differences in oxycodone metabolism but the findings are inconsistent and the clinical relevance of these findings is uncertain [6-8].
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. Thus, dosing of opioids must be individualized [9].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 [10].
Effects
The effect of opioids for pain-relief may differ between men and women. According to a systematic review, women may require lower doses of opioids, both in treatment of acute and chronic pain. However, no specific data on oxycodone for treatment of acute pain were presented [11].
Adverse effects
Sex differences in opioid response were investigated in a large retrospective cohort study (3319 men, 5138 women). Women were twice as likely as men to report adverse reactions to oxycodone after adjusting for BMI and age (OR 2.2). For opioids in general, women had a higher risk of gastrointestinal issues (OR 3.1), skin and subcutaneous tissue complications (e.g. rash, itching; OR 2.1), and nervous system issues (e.g. migraines, dizziness; OR 2.3) [12].
Reproductive health issues
Regarding teratogenic aspects, please consult Janusmed Drugs and Birth Defects (in Swedish, Janusmed fosterpåverkan).
Updated: 2022-12-22
Date of litterature search: 2022-11-19
References
- 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
- Bartley EJ, Fillingim RB. Sex differences in pain: a brief review of clinical and experimental findings. Br J Anaesth. 2013;111(1):52-8. PubMed
- Sorge RE, Totsch SK. Sex Differences in Pain. J Neurosci Res. 2017;95(6):1271-1281. PubMed
- Dance A. Why the sexes don't feel pain the same way. Nature. 2019;567(7749):448-450. PubMed
- 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
- 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
- Harris RZ, Benet LZ, Schwartz JB. Gender effects in pharmacokinetics and pharmacodynamics. Drugs. 1995;50:222-39. PubMed
- 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
- OxyNorm (oxycodone). Summary of Product Characteristics. Swedish Medical Products Agency [updated 2022-06-21, cited 2022-11-19]
- 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
- Pisanu C, Franconi F, Gessa GL, Mameli S, Pisanu GM, Campesi I et al. Sex differences in the response to opioids for pain relief: A systematic review and meta-analysis. Pharmacol Res. 2019;148:104447. PubMed
- Lopes GS, Bielinski S, Moyer AM, Jacobson DJ, Wang L, Jiang R et al. Sex differences in type and occurrence of adverse reactions to opioid analgesics: a retrospective cohort study. BMJ Open. 2021;11(6):e044157. PubMed
- Statistikdatabas för läkemedel. Stockholm: Socialstyrelsen. 2021 [cited 2022-03-15.] länk
Reviewed by: Carl-Olav Stiller, Pauline Raaschou
Approved by: Karin Schenck-Gustafsson