Preparat: Abstral, Actiq®, Durogesic®, Effentora, Fentanyl Actavis, Fentanyl Hexal, Fentanyl Lavipharm, Fentanyl Mylan, Fentanyl Orion, Fentanyl ratiopharm, Fentanyl Sandoz, Fentanyl Takeda, Instanyl, IONSYS, Ionsys®, Matrifen, PecFent
ATC kod: N02AB03
Substanser: fentanyl, fentanylcitrat, fentanylhydroklorid
Fentanyl används vid cancerrelaterad smärta då peroral opioidbehandling inte kan ges.
Förekomst av opiatinducerat illamående är högre hos kvinnor.
Kunskapsunderlaget avseende skillnader mellan kvinnor och män är begränsat och motiverar inte olika dosering eller behandling. Som med andra opiater skall fentanyl titreras för att hitta lägsta effektiva dos.
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 .
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 . 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 . 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 . 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 . 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) . Women have been shown to have more discomfort during colonoscopy (44 men, 65 women) . 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 .
No studies with a clinically relevant sex analysis regarding the effects of fentanyl have been found.
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%) . 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.
Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).
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%) .
Fler kvinnor än män hämtade ut läkemedel innehållande fentanyl (ATC-kod N02AB03) på recept i Sverige år 2015, totalt 14 040 kvinnor och 7 849 män. Det motsvarar 2,9 respektive 1,6 personer per tusen invånare. Andelen som hämtat ut läkemedel var högst i åldersgruppen 85 år och äldre hos båda könen. I genomsnitt var läkemedel innehållande fentanyl 1,5 gånger vanligare hos kvinnor . Observera att ATC-koden N02AB03 innehåller fentanyl i beredningsformerna plåster, sugtablett, buckaltablett, resoriblett och nässpray. Prevalens för kronisk smärta är högre hos kvinnor [13, 14].
Faktagranskat av: Mia von Euler, Carl-Olav Stiller
Godkänt av: Karin Schenck-Gustafsson