A Study on Neurotoxic Medications

Neurologists Louis H. Weimer of Columbia University and David Podwall of the Albert Einstein College of medicine note that while “existing peripheral neuropathy is a generally accepted risk factor for increased susceptibility to neurotoxic agents,” there is some question whether CMT patients should avoid neurotoxic medications even when their use is clearly indicated. The extensive distribution of the list of neurotoxic medications raises the additional concern that, in some cases, an inordinate degree of perceived risk could deter the use of a preferred medication for a condition unrelated to CMT.

NeuroMeds : download full text.

Weimer and Podwall conducted an extensive literature search and found that 22 of 26 reports of neurotoxicity in CMT patients concerned vincristine, a chemotherapeutic agent (listed on Medical Alert as “definite high risk”). The remainder concerned nucleoside analogs and taxoids (which fall in the “moderate to significant risk” category).

They also reviewed data from the CMT North American Database,* a computerized registry of clinical details of CMT patients in the U.S. and Canada. The database provided 996 drug entries of 209 persons from 190 families. Medications with multiple reported exposures and more than one claim of symptomatic worsening of neuropathy included metronidazole, nitrous oxide, statins, nitrofurantoin, phenytoin, and sertraline. Others (isoniazid, penicillin — high IV doses) had 1 or 2 adverse reports. Still other agents were notable for exposures without reported neuropathic effect. These included adriamycin, chloramphenicol, dapsone, disulfiram, hydralazine, lithium, and pyridoxine.

Overall, Weimer and Podwall conclude that treatment with vincristine poses an “unacceptable risk to patients with known or possible CMT1A.” They further conclude that the use of other agents in the significant risk category of the list should be considered with caution, and “the probable lesser risk of agents in lower categories should also be weighed when prescribing these drugs for people with CMT.”

At the same time, however, Weimer and Podwall are careful to point out that these conclusions are based on limited direct evidence, and that there are several possible explanations for the lack of documentation in the literature regarding adverse effects of many of the drugs on the CMTA neurotoxic drug list.

In particular, cases of worsening of neuropathy may by unreported or unrecognized, so it is still prudent to make your treating physician aware that drugs on the Medical Alert list may have the potential to adversely affect someone with CMT and to discuss alternative medications. More importantly, if you begin taking any of the medications on the list, or any other medication, and you notice a change in your condition, you should notify your physician immediately.

*The CMT North American Database was initiated at Wayne State University. Funded by the Charcot-Marie-Tooth Association and the Muscular Dystrophy Association, it is currently maintained in the Department of Medical and Molecular Genetics at Indiana University.

The study conducted by Weimer and Podwall demonstrated the potential of the database project to provide researchers with the information needed to answer important questions regarding the treatment and management of CMT. At the same time, the study pointed out the limitations of the current data and the need for more people with CMT to contribute their information.