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Fentanyl

Classification: A

Drug products: Abstral, Actiq®, Durogesic®, Effentora, Fentanyl 2care4, Fentanyl Actavis, Fentanyl Citrate Injection USP, Fentanyl Hexal, Fentanyl Lavipharm, Fentanyl Mylan, Fentanyl Orion, Fentanyl ratiopharm, Fentanyl Sandoz, Fentanyl Takeda, Instanyl, IONSYS, Ionsys®, Matrifen, PecFent

ATC code: N02AB03

Substances: fentanyl, fentanyl citrate, fentanyl hydrochloride

Summary

Fentanyl is used in cancer-related pain when other oral opiates can’t be used. Opiod-induced nausea has been shown to be higher in women.

The present evidence concerning differences between men and women is limited and do not motivate differentiation in dosing or treatment.
As with other opiates, fentanyl should be titrated to find the lowest effective dose.

Additional information

The literature indicates that women and men differ in pain behavior. 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 are higher in women than men 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].

Pharmacokinetics and dosing

Delivery rate of transdermal fentanyl patches in patients undergoing palliative care has been investigated (33 men, 35 women). Sex did not influence fentanyl transdermal delivery. Also, a pharmacokinetic model describing the relationship between fentanyl transdermal dose rate and urinary fentanyl excretion was established and showed fentanyl excretion for higher transdermal doses (>75 µg/h) to be substantially lower for women than men. This could theoretically lead to risk for accumulations of fentanyl in the body and hence more adverse effects [3]. The clinical relevance of this study is unclear.In a randomized, open-label, crossover study in healthy volunteers (21 men, 13 women) no sex difference in AUC was found when fentanyl was applied transdermal, 40 µg to the arm, and after a wash out period, intravenously 120 µg [4]. In patients, a small study (8 men, 5 women) found no sex differences in steady-state concentration or bioavailability of transdermal fentanyl in doses 50-125 µg/h [5]. Another pharmacokinetic study of transdermal fentanyl 25-500 µg/h in oncology patients (71 men and 37 women) no sex differences were found. However, large variation in absorption of the drug was found both between individuals and between different cancer forms [6]. If the two latter studies were powered to detect clinical significant sex differences is unclear.

In a study analyzing colonoscopies performed for colorectal cancer screening (348 men, 425 women), women required higher doses of i.v. fentanyl for sedation (women: 166.9 µg + 2.7; men: 157.3 µg + 3.0, p=0.016) [7]. Women have been shown to have more discomfort during colonoscopy (44 men, 65 women) [8]. If the need of more fentanyl in women reflects a higher discomfort or less effect of fentanyl is not known.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

No studies with a clinically relevant sex analysis regarding the effects of fentanyl have been found.

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%) [9]. Also, studies on postoperative opioid-induced nausea and emesis have shown this to be higher in women than in men [10, 11]. If this is due to the medication was not explored in these studies.

Reproductive health issues

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

Other information

In a retrospective analysis of pharmacy records in North America (3631 men, 3570 women), transdermal fentanyl was prescribed more often to women than men (46.3% vs. 37.2%) [2].

Updated: 2019-02-26

Date of litterature search: 2015-01-27

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. 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
  3. Van Nimmen NF, Poels KL, Menten JJ, Godderis L, Veulemans HA. Fentanyl transdermal absorption linked to pharmacokinetic characteristics in patients undergoing palliative care. J Clin Pharmacol. 2010;50:667-78. PubMed
  4. Gupta SK, Hwang S, Southam M, Sathyan G. Effects of application site and subject demographics on the pharmacokinetics of fentanyl HCl patient-controlled transdermal system (PCTS). Clin Pharmacokinet. 2005;44 Suppl 1:25-32. PubMed
  5. Gourlay GK, Kowalski SR, Plummer JL, Cherry DA, Gaukroger P, Cousins MJ. The transdermal administration of fentanyl in the treatment of postoperative pain: pharmacokinetics and pharmacodynamic effects. Pain. 1989;37:193-202. PubMed
  6. Solassol I, Caumette L, Bressolle F, Garcia F, Thézenas S, Astre C et al. Inter- and intra-individual variability in transdermal fentanyl absorption in cancer pain patients. Oncol Rep. 2005;14:1029-36. PubMed
  7. Czwornog J, Austin GL. Body mass index, age, and gender affect prep quality, sedation use, and procedure time during screening colonoscopy. Dig Dis Sci. 2013;58:3127-33. PubMed
  8. Elphick DA, Donnelly MT, Smith KS, Riley SA. Factors associated with abdominal discomfort during colonoscopy: a prospective analysis. Eur J Gastroenterol Hepatol. 2009;21:1076-82. PubMed
  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. Zun LS, Downey LV, Gossman W, Rosenbaumdagger J, Sussman G. Gender differences in narcotic-induced emesis in the ED. Am J Emerg Med. 2002;20:151-4. PubMed
  11. Koivuranta M, Läärä E, Snåre L, Alahuhta S. A survey of postoperative nausea and vomiting. Anaesthesia. 1997;52:443-9. 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, Carl-Olav Stiller

Approved by: Karin Schenck-Gustafsson

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