Drug products: Buprefarm, Bupremyl, Buprenorfin Actavis, Buprenorfin Evolan, Buprenorphine Bluefish, Buprenorphine Ethypharm, Buprenorphine G.L. Pharma, Buprenorphine Glenmark, Buprenorphine Orifarm, Buprenorphine Sandoz, Buprenorphine STADA, Buprenorphine Teva, Buvidal, Espranor, Norspan, Norspan®, Sublocade, Subutex, Subutex®, Temgesic, Temgesic®, Transtec
ATC code: N02AE01, N07BC01
Substances: buprenorphine, buprenorphine hydrochloride
Buprenorphine is used both to treat pain and to treat opiod dependency. Both men and women have been shown beneficial effect in treatment of opioid dependency.
Based on the present evidence, there is no reason to generally differentiate the treatment in men and women. As with all opioids, the lowest effective dose should be used.
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 .
In a retrospective study, men and women received the same daily dose of sublingual buprenorphine/naloxone 16/4 mg. Women had higher AUC and Cmax for buprenorphine and the metabolites norbuprenorphine and norbuprenorphine-3-glucuronide. When the results were adjusted for lean body mass, there were no sex differences in AUCs .Pooled data from pharmacokinetic studies conducted by the sponsor showed no sex differences in Cmax and AUC. NONMEM analysis showed that increasing age and sex contributed to a 20% lower clearance. Since buprenorphine sublingual tablet (Subutex®) is a titratable drug and the predicted decrease in clearance is only 20%, no dosage adjustments are recommended .The effect of sex on transdermal buprenorphine pharmacokinetics has been investigated by the original manufacturer using analysis of pooled clinical pharmacology studies. No significant effect of sex was observed in Cmax and AUC .
Buprenorphine is dosed according to effect and thus individualized. Pharmacokinetic studies show no difference between men and women when correlated for bodyweight and age and thus, if these factors are considered similar doses should be used.
A randomized controlled study (104 men, 61 women) evaluating the impact of sex on opioid agonist treatment found both men and women to benefit from buprenorphine treatment (dosing 16-32 mg) .
A randomized controlled trial found that no patients taking buprenorphine (36 men, 18 women) experienced a QT prolongation even though buprenorphine in vitro blocks the human hERG channel which is strongly associated with QT prolongation and a risk of Torsades de pointes ventricular tachycardia . Among the known risk factors of drug-induced ventricular arrhythmias are female sex, hypokalemia, bradycardia, and base line QT-prolongation .
Regarding teratogenic aspects, please consult the Drugs and Birth Defects Database (in Swedish, Janusmed fosterpåverkan).
One study on buprenorphine in patients with former drug abuse reported that women receiving buprenorphine had fewer illegitimate opioid-positive urine samples than men . However, another study reported that women receiving buprenorphine showed greater rates of illegitimate opioid use than men . These different results could be explained by different study designs and different durations of treatment, but also by differences in pharmacodynamics .
Date of litterature search: 2015-02-12
Reviewed by: Mia von Euler
Approved by: Karin Schenck-Gustafsson