In this episode, I’ll discuss how rifampin affects hydromorphone levels.
A recent review article published in Pharmacotherapy concluded that:
…Decreased effect of opioids with concomitant rifampin therapy manifested as…a decreased analgesic effect from tramadol, morphine, and, most notably, oxycodone…
However, this systematic review did not identify any articles that evaluated the effects of rifampin on hydromorphone.
A few months later, in the journal Anesthesia and Analgesia, a group of authors report results of a paired, randomized, crossover study looking at the effect of rifampin on hydromorphone levels in healthy volunteers.
Participants received oral placebo or rifampin for 8 days. A single dose of 2.6 mg oral hydromorphone was administered on day 6 followed by 0.02 mg/kg IV hydromorphone on day 8.
The authors measured hydromorphone and metabolite plasma concentrations for 24 hours, as well as participants’ perceived drug effect, change in pupil diameter, and cold pressor threshold for 6 hours. Pharmacodynamic and kinetic properties were also measured as secondary outcomes.
Because the study participants were healthy volunteers and not patients in pain, it is difficult to interpret the results. On one hand, none of the measures of drug effect, pupil size, and cold pressor threshold were significantly different between groups. On the other hand, rifampin reduced the areas under the plasma concentration–time curves of oral and intravenous hydromorphone by 43% and 26%, respectively. The maximum plasma concentration of oral hydromorphone was also reduced by 37%.
These pharmacokinetic effects appear significant however it is not clear whether a difference in analgesic effect from hydromorphone would occur with rifampin use, however, the authors believe this interaction is clinically significant.
A few interesting concepts unrelated to hydromorphone can also be gleaned from this article. First, the authors waited for 6 days of rifampin therapy before administering hydromorphone, so enzyme induction can be expected to be clinically significant after 6 days of rifampin therapy. Second, in order to confirm enzyme induction had occurred the authors took a method used to identify CYP3A4 activity in liver transplant patients: a midazolam metabolic clearance test. Using this method, if midazolam clearance can be calculated then it can be correlated to the degree of CYP3A4 activity.
To access my free download area with 20 different resources to help you in your practice, go to pharmacyjoe.com/free.
If you like this post, check out my book – A Pharmacist’s Guide to Inpatient Medical Emergencies: How to respond to code blue, rapid response calls, and other medical emergencies.