WARNING: Methadone should only be prescribed for pain by experienced clinicians!
Indubitably, the most difficult opioid conversion challenge to prescribers and pharmacists is methadone.
Methadone to Morphine (or equivalent) ≠ Morphine (or equivalent) to Methadone
Methadone conversion calculations cannot be bidirectional because the half-life of methadone is long, approximately 15-60 hours. Methadone therefore stays in the body for several days after discontinuation. In essence, after calculating a conversion to morphine (or equivalent), one cannot simply stop the methadone and substitute with the equivalent dose because both drugs will remain in the body. Careful slow titration and transition to or from methadone is vital.
Furthermore, significant pharmacokinetic intrapatient variability exists as a result of polymorphism, hence the huge half-life variation (15-60, and up to 150 hours). And, if that’s not enough to challenge you, methadone undergoes Cytochrome P450 metabolism, 3A4, 2B6, 2C8, 2C9,2C19, and 2D6 mediated N-demethylation to 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidene (EDDP). This of course precipitates yet another issue, significant risk for drug interactions!
If the clinician can get past all these barriers, we are often left with the daunting task of converting other opioids to an equivalent dose of methadone. Online opioid conversion calculators have been shown to vary in methadone calculation by up to 242% (Presented by Dr. Kathryn C. Shaw, Eastern States Residency Conference, Hershey PA; May 2012), which could easily be fatal. In fact, methadone accounts for 2% of all opioids prescribed in the U.S., yet 33% of all opioid-related deaths from overdose involve methadone. When a healthcare practitioner transitions a patient to methadone, a potential disparity in calculated dose conversions is in large part due to varying methadone conversion schematics that have heretofore by some, been considered acceptable standards. These were suggested by Ripamonti(1998), Ayonrinde(2000), and Mercadente(2001). Fourteen years have passed since Ripamonti’s original proposed schematic, yet until now, nobody has graphed the three strategies against one another to show the irrationality in terms of peaks and troughs over several hundred milligrams.
Graphing these schematics spurred my initiative to develop a formula that would smooth out the methadone conversion curve. Hence, the Fudin Factor, a methadone conversion equation (Copyright, 2011) was derived.
A feature article appears in the September 2012 issue of Practical Pain Management that details the equation. Click on “Mathematical Model for Methadone Conversion Examined” to read about the history of methadone, view a comparison of previously accepted schematics outlined herein, and learn about the derivation of the FUDIN FACTOR, inherent limitations, and how it compares to Ripamonti, Ayonrinde, and Mercadente.
AS ALWAYS, YOUR THOUGHTFUL COMMENTS (PRO OR CON) BELOW ARE WELCOMED, ENCOURAGED, AND MET WITH ENTHUSIASM!