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Supporting people affected by Charcot-Marie-Tooth disease.

Neurotoxic Medications

The medications listed below are potentially toxic to CMT patients. Vincristine has been proven hazardous and should be avoided by all CMT patients, including those with no symptoms. The remainder of the medications listed below present varying degrees of potential risk for worsening CMT neuropathy.

Before taking any medication or changing medication, all CMT patients should make sure the treating physician is fully aware of their medical condition.

Please be aware that this list is taken from a US website, and some of the drugs may not be available in the UK, or may be marketed under different names.

Click here to view expanded Medical Alert table.

Definite High Risk (including asymptomatic CMT)

  • Vinca alkaloids (Vincristine)
  • Taxols (paclitaxel, docetaxel, cabazitaxel)

Moderate to Significant Risk

  • Amiodarone (Cordarone)
  • Arsenic Trioxide (Trisenox)
  • Bortezomib (Velcade)
  • Brentuximab Vedotin(Adcetris)
  • Cetuximab (Erbitux)
  • Cisplatin & Oxaliplatin
  • Colchicine (extended use)
  • Dapsone
  • Didanosine (ddI, Videx)
  • Dichloroacetate
  • Disulfiram (Antabuse)
  • Eribulin (Halaven)
  • Fluoroquinolones
  • Gold salts
  • Ipilimumab (Yervoy)
  • Ixabepilone (Ixempra)
  • Leflunomide (Arava)
  • Lenalidomide (Revlimid)
  • Metronidazole/Misonidazole (extended use)
  • Nitrofurantoin (Macrodantin, Furadantin, Macrobid)
  • Nitrous oxide (inhalation abuse or Vitamin B12 deficiency)
  • Nivolumab (Opdivo)
  • Pembrolizumab (Keytruda)
  • Perhexiline (not used in U.S.)
  • Pertuzumab (Perjeta)
  • Pomalidomide (Pomalyst)
  • Pyridoxine (Although megadoses [10 times or more the RDA] of Vitamin B6 may be harmful, high intakes of vitamin B6 from food sources have not been reported to cause adverse effects.) NIH Fact Sheet
  • Stavudine (d4T, Zerit)
  • Suramin
  • Thalidomide
  • Zalcitabine (ddC, Hivid)

Uncertain or Minor Risk

  • 5-Fluoracil
  • Adriamycin
  • Almitrine (not in U.S.)
  • Chloroquine
  • Cytarabine (high dose)
  • Ethambutol
  • Etoposide (VP-16)
  • Gemcitabine
  • Griseofulvin
  • Hexamethylmelamine
  • Hydralazine
  • Ifosphamide
  • Infliximab
  • Isoniazid (INH)
  • Lansoprazole (Prevacid)
  • Mefloquine
  • Omeprazole (Prilosec)
  • Penicillamine
  • Phenytoin (Dilantin)
  • Podophyllin resin
  • Sertraline (Zoloft)
  • Statins
  • Tacrolimus (FK506, ProGraf)
  • Zimeldine (not in U.S.)
  • a-Interferon

 Negligible or Doubtful Risk

  • Allopurinol
  • Amitriptyline
  • Chloramphenicol
  • Chlorprothixene
  • Cimetidine
  • Clioquinil
  • Clofibrate
  • Cyclosporin A
  • Enalapril
  • Gluthethimide
  • Lithium
  • Phenelzine
  • Propafenone
  • Sulfonamides
  • Sulphasalzine

A Note about Alcohol

Alcohol was removed from the neurotoxic drug list in July 2004.  While people with CMT generally suffer no ill effects from the moderate consumption of alcohol, they should be particularly mindful of the fact that alcohol affects balance and coordination, and that overconsumption of alcohol is generally not recommend under any circumstances.

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 the full text here.

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 be 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 a patient begins taking any of the medications on the list, or any other medication, and notices a change in  their condition, they should return to their doctor for review.

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 demonstrates 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 points out the limitations of the current data, and the need for more people with CMT to contribute their information.

 

 

 

Many thanks to Charcot-Marie-Tooth Association (www.cmtausa.org) for allowing us to share their information with you.

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