Drug Interactions between abiraterone and ConZip

GENERALLY AVOID: Coadministration of androgen deprivation therapy (ADT) with other agents that may prolong the QT interval, like tramadol, could result in additive effects and an increased risk of ventricular arrhythmias including torsade de pointes and sudden death. These risks may be greater in patients with certain underlying risk factors like congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). Studies in young men have shown that endogenous serum testosterone levels are inversely associated with QTc (QT interval corrected for heart rate) duration. Clinical trials in men with low serum testosterone levels have reported testosterone administration being associated with a shortening of QTc. Likewise, studies using ADT have shown that it may prolong the QT interval; however, this effect may not be the same with each drug, dose, or even each drug class that can be used to reduce testosterone levels. Abiraterone specifically carries a risk of hypokalemia, which is a known risk factor for QT prolongation and torsade de pointes. Both conditions have been reported as being associated with abiraterone use in postmarketing reports. Tramadol has also had cases of QT prolongation and/or torsade de pointes reported in association with its use. Many of these cases were reported in patients taking another drug that could cause QT prolongation, in patients with a risk factor for QT prolongation such as hypokalemia, or in the overdose setting.

GENERALLY AVOID: Coadministration with abiraterone acetate may decrease the opioid-like effects of tramadol via inhibition of CYP450 2D6, the isoenzyme used to convert tramadol to its active metabolite, M1. In animal studies, M1 was up to 6 times more potent than tramadol in producing analgesia and 200 times more potent in binding to mu-opioid receptors. Clinical data are lacking.

MANAGEMENT: Concomitant use of abiraterone and tramadol should generally be avoided. If coadministration is required, careful consideration of the effects on tramadol and M1 is required. Patients should be monitored for opioid withdrawal, seizures, and serotonin syndrome, and care should be exercised in patients suspected to be at an increased risk of torsade de pointes. If abiraterone is discontinued, consider reducing the tramadol dose until stable drug effects are achieved and monitor for respiratory depression and sedation. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

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