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Buprenorphine

Classification: A

Drug products: Buprefarm, Bupremyl, Buprenorfin Actavis, Buprenorfin Evolan, Buprenorphine 2care4, Buprenorphine Bluefish, Buprenorphine Ethypharm, Buprenorphine G.L. Pharma, Buprenorphine Glenmark, Buprenorphine Orifarm, Buprenorphine Sandoz, Buprenorphine STADA, Buprenorphine Teva, Buvidal, Espranor, Norspan, Norspan®, Sixmo, Sublocade, Subutex, Subutex®, Temgesic, Temgesic®, Transtec

ATC code: N02AE01, N07BC01

Substances: buprenorphine, buprenorphine hydrochloride

Summary

Buprenorphine is used to treat pain and to treat opioid dependency. Analyses of differences between men and women in pain-relief response of buprenorphine are lacking. Beneficial treatment effect in opioid dependency has been shown for both men and women.  The lowest effective dose should be used.

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].

Pharmacokinetics and dosing

Buprenorphine is dosed according to effect and thus dosing should be individualized. Due to extensive first-pass effect sublingual or transdermal administration is common. If the dose is based on age and body weight the pharmacokinetic profile of sublingual and transdermal buprenorphine does not differ between men and women and similar doses should be used [5-7].

Effects

The effect of opioids for pain-relief may differ between men and women. Women may require lower doses of opioids, both in treatment of acute and chronic pain [8]. However, no studies on buprenorphine were included in the meta-analysis. No studies with a sex analysis regarding the effects of buprenorphine have been found.A randomized controlled study (104 men, 61 women) on the impact of patient’s sex on opioid agonist treatment in opioid use disorder indicates that  both men and women benefit from buprenorphine treatment (dosing 16-32 mg), but females maintained on buprenorphine had significantly fewer opioid-positive urine samples compared to males [9].Some studies report different rates of treatment retention to buprenorphine in men and women [10]. However, a meta-analysis published in 2022 indicates similar rates of treatment retention (for opioid use disorder) in men and women [11].

Adverse effects

One meta-analysis of clinical trial data found no sex differences in weight change after 12 weeks of buprenorphine treatment [12].Buprenorphine blocks the human hERG channel which is strongly associated with QT prolongation and risk of Torsades de Pointes ventricular tachycardia. A randomized controlled trial found that no patients taking buprenorphine (36 men, 18 women) experienced a QT prolongation [13]. Known risk factors of drug-induced ventricular arrhythmias are female sex, hypokalemia, bradycardia, and base line QT-prolongation [14].

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: 2015-02-12

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. 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
  3. Sorge RE, Totsch SK. Sex Differences in Pain. J Neurosci Res. 2017;95(6):1271-1281. PubMed
  4. Dance A. Why the sexes don't feel pain the same way. Nature. 2019;567(7749):448-450. PubMed
  5. Moody DE, Fang WB, Morrison J, McCance-Katz E. Gender differences in pharmacokinetics of maintenance dosed buprenorphine. Drug Alcohol Depend. 2011;118:479-83. PubMed
  6. Food and Drug Administration (FDA). Clinical Pharmacology and Biopharmaceutics Review - SUBUTEX (buprenorphine) [updated 2002-10-08]. länk
  7. Food and Drug Administration (FDA). Clinical Pharmacology and Biopharmaceutics Review - BUTRANS (buprenorphine) [updated 2010-06-30]. länk
  8. 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
  9. Jones HE, Fitzgerald H, Johnson RE. Males and females differ in response to opioid agonist medications. Am J Addict. 2005;14:223-33. PubMed
  10. Ling S, Mangaoil R, Cleverley K, Sproule B, Puts M. A systematic review of sex differences in treatment outcomes among people with opioid use disorder receiving buprenorphine maintenance versus other treatment conditions. Drug Alcohol Depend. 2019;197:168-182. PubMed
  11. Hochheimer M, Unick GJ. Systematic review and meta-analysis of retention in treatment using medications for opioid use disorder by medication, race/ethnicity, and gender in the United States. Addict Behav. 2022;124:107113. PubMed
  12. Manza P, Kroll D, McPherson KL, Johnson A, Dennis E, Hu L et al. Sex differences in weight gain during medication-based treatment for opioid use disorder: A meta-analysis and retrospective analysis of clinical trial data. Drug Alcohol Depend. 2022;238:109575. PubMed
  13. Wedam EF, Bigelow GE, Johnson RE, Nuzzo PA, Haigney MC. QT-interval effects of methadone, levomethadyl, and buprenorphine in a randomized trial. Arch Intern Med. 2007;167:2469-75. PubMed
  14. Roden DM. Drug-induced prolongation of the QT interval. N Engl J Med. 2004;350:1013-22. PubMed
  15. Statistikdatabas för läkemedel. Stockholm: Socialstyrelsen. 2021 [cited 2022-03-15.] länk
  16. 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
  17. 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

Reviewed by: Carl-Olav Stiller, Pauline Raaschou

Approved by: Karin Schenck-Gustafsson