Buprenorfin

Additional information

The scientific literature indicates that pain behavior and pain perception may vary between men and women. 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 is higher in women than in men, which 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]. Therefore, sex differences of pain releasing medication might thus be difficult to interpret [2].

Pharmacokinetics and dosing

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 [2].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 [3].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 [4].

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.

Effects

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) [5].

Adverse effects

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 [6]. Among the known risk factors of drug-induced ventricular arrhythmias are female sex, hypokalemia, bradycardia, and base line QT-prolongation [7].

Reproductive health issues

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

Other information

One study on buprenorphine in patients with former drug abuse reported that women receiving buprenorphine had fewer illegitimate opioid-positive urine samples than men [8]. However, another study reported that women receiving buprenorphine showed greater rates of illegitimate opioid use than men [8]. These different results could be explained by different study designs and different durations of treatment, but also by differences in pharmacodynamics [9].