Pharmacogenetic testing may also be helpful, Dr. Fudin explained, to identify the potential benefits and risks of certain medications, such as methadone, prior to prescribing or continuing treatment. 

Due to its make-up, “methadone has unique pharmacokinetic characteristics and for this reason has been associated with distinctive and serious toxicity compared with other opioids,” he cautioned. 

Methadone is a racemic mixture of the (R) and (S) isomers.

The (R)-enantiomer is primarily responsible for analgesic effects while the (S)-enantiomer is associated with cardiotoxic adverse effects, specifically prolongation of the heart-rate corrected QT (QTc) interval, Dr. Fudin explained. Both isomers are metabolized to the inactive metabolite, EDDP, but through different pathways.

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(R)-methadone is metabolized primarily by CYP3A4 (but other CYP enzymes have a lesser role, including 2C19 and 2D6). (S)-methadone is primarily metabolized by CYP2B6;  thus, he said, a poor metabolizer of CYP2B6 would be at increased risk for buildup of the cardiotoxic S-enantiomer and at higher risk for QTc prolongation and arrhythmia associated with sudden death. 

Knowing this information through testing, prior to prescribing, may be helpful to minimize the risk of a potentially serious or fatal toxicity, according to Dr. Fudin. 

Dr. Fudin reports he is a member of the speakers’ bureau for Millennium Health, LLC; he is also a consultant for AstraZeneca, Millennium Health LLC, Kaléo Pharma, Zogenix, and Depomed.

This article originally appeared on MPR