Are Flawed Dose Conversion Calculators to Blame for the Dramatic Increase in the Number of Methadone Overdoses?

Although methadone accounts for only 2% of opioid prescriptions, it caused nearly one in 3 prescription opioid overdose deaths in 2012, according to CDC statistics shared by Jeffrey Fudin, BS, PharmD, FCCP, DAAPM, at the 2014 annual clinical meeting of the American Academy of Pain Management, in Phoenix, AZ. Furthermore, this is a 6-fold increase from 2009. Fudin said that evidence published in an article in Pain Medicine in 2012 “suggests that the use of dose conversion ratios published in equianalgesic tables may lead to fatal or near-fatal opioid overdoses.”

Fudin is the Clinical Pharmacy Specialist and Director of PGY2 Pain and Palliative Care Pharmacy Pain Residency at the Stratton VA Medical Center in Albany, NY, and owner and managing editor of PainDr.com.

He said opioid rotation is common in clinical practice for several reasons. For example, opioids may be switched when pain is not under control and doses cannot be escalated, when adverse events or toxicity occurs, when patients develop rapid tolerance, or when opioid-induced hyperalgesia is suspected. Specifically in chronic pain patients, opioid rotation is reported to offer better pain control, and due to patient differences, opioid rotation may be required to find the best fit. Opioid conversion doses can be found in package inserts, primary literature, textbooks, websites, and online calculators. Many members of the audience raised their hands when asked who regularly made use of online conversion calculators. Fudin said he was not surprised by this.

In fact, Fudin has done extensive analysis of both manual calculations and online calculators. At the educational session, he described the interesting results from a paper he published in Practical Pain Management in 2013. After conducting a literature search, Fudin and his team found eight online opioid conversion calculators; after evaluating the calculators for accuracy and the ability to perform the variety of required calculations, two calculators — WA State Agency and Med Cal – were removed from the analysis. When the remaining calculators were compared to each other, a +242% variation in recommended methadone does was seen in the results. A positive variation carries a risk of overdose and death, while a negative variation carries a risk of underdose and withdrawal, Fudin explained. He also reported a +100% variation for fentanyl.

Fudin has also studied the top mathematical models for calculating opioid conversion doses, and he has developed his own formula using the most conservative approach. Fudin’s formula, for example, calculates a 302.5 mg dose of morphine would convert to a 30 mg dose of methadone; in comparison, one formula in his study calculated a conversion dose of 60 mg of methadone for replacing a 300 mg dose of morphine. Fudin’s formula has now been incorporated into the online calculator that is available on the Practical Pain Management website.

Even an accurate online calculator requires extreme care to ensure that numbers are entered correctly, and all calculations should be evaluated with clinical expertise. “Slow titration, clinical judgment, and individualization of treatment are necessary to safely and effectively switch a patient from one or more opioids to another,” Fudin concluded.