Charcot-Marie-Tooth disease (CMT) is named after the three doctors who first described the disease in 1886: Jean-Martin Charcot (shar-coh), Pierre Marie, and Howard Henry Tooth. Today, CMT refers to any peripheral neuropathy with a genetic cause, whether or not the specific genetic mutation is known.
CMT is a rare multisystem, multiorgan disease that causes lifelong, progressive symptoms, including muscle weakness and atrophy in the arms and legs, sensory loss, and other complications. Certain medications can worsen symptoms or negatively interact with the underlying biology of CMT. CMTA has undertaken rigorous scientific reviews to identify these potential risks and provide evidence-based information for individuals with CMT and their healthcare providers.
Disclaimer: This page is for informational purposes only and is not intended to serve as medical advice, nor should any information on this page replace the advice of a qualified healthcare provider. Always consult a qualified healthcare provider about medication questions or concerns and follow their advice.
What is a Neurotoxic Medication?
A neurotoxic medication is a drug that can cause or worsen peripheral neuropathy symptoms. For someone with CMT, this might temporarily increase symptoms such as numbness, tingling, or muscle weakness. These effects often improve once the medication is discontinued, though responses may vary from person to person.
Why Neurotoxic Medications Are a Potential Concern in CMT
Certain medications, known as neurotoxic drugs, can harm peripheral nerves and worsen symptoms for individuals with CMT. These drugs can exacerbate nerve damage, potentially leading to increased muscle weakness, sensory loss, or other complications. The specific effects often depend on the type of CMT, such as demyelinating (CMT1) or axonal (CMT2).
Recognizing these potential risks is important for patients, caregivers, and healthcare providers when making informed decisions about treatment options. CMTA’s information on this page is grounded in evidence-based scientific research to provide the best available information for discussions with healthcare providers.
CMTA’s Neurotoxic Medications Review
The Original CMTA Neurotoxic Drug List
CMTA initially published a comprehensive list of neurotoxic medications many years ago. Given its age, it became clear that a review was needed as scientific knowledge advanced. CMTA commissioned a review in 2022 to evaluate new evidence and update the available information if warranted.
The 2022 Review
In 2022, CMTA commissioned a thorough scientific reevaluation of the CMTA Neurotoxic Drug List. Led by neurotoxic drug experts Guido Cavaletti, MD and Paola Alberti, MD, PhD, with CMTA Chief Research Officer Katherine Forsey, PhD, this systematic review analyzed current research and clinical data to determine which drugs, if any, posed significant risks for individuals with CMT. The outcome was a streamlined list of just two drugs identified as having evidence-backed potential for harm. The review was published in the Journal of the Peripheral Nervous System and can be downloaded here.
The Two Drugs of Concern
Vincristine
The reviewers identified the cancer drug Vincristine as a potentially significant risk for individuals with CMT. The drug manufacturer, Pfizer, warns that Vincristine Sulfate injections should not be given to individuals with “the demyelinating form of Charcot-Marie-Tooth disease.”
- Potential Risks of Concern: Research shows that Vincristine’s neurotoxic effects can exacerbate nerve damage, leading to severe and sometimes irreversible worsening of CMT symptoms. Healthcare providers and individuals with demyelinating types of CMT must understand these potential risks when considering treatment options related to the individual’s diagnosis.
- Reference: For more information, see the official Pfizer Medical Information – Vincristine Sulfate Injection Contraindications.
Paclitaxel
Paclitaxel is the reviewers’ other drug of concern due to its known association with neurotoxicity. This drug is reported to cause peripheral neuropathy, which may be of special concern to individuals with CMT and their healthcare providers.
- Potential Risks of Concern: A 2017 study highlighted the potential for Paclitaxel to worsen peripheral neuropathy in patients with CMT caused by mutations of the MFN2 gene (CMT2A, CMT2A2B, CMT2B4, and HMSN-6A), ARHGEF10 gene (CMT-ARHGEF10), and the PRX gene (CMT4F). The research suggests that Paclitaxel’s neurotoxic effects can exacerbate nerve damage, leading to severe and sometimes irreversible worsening of CMT symptoms. When considering treatment options, healthcare providers and individuals with these CMT subtypes must understand these potential risks.
- Reference: Paclitaxel in CMT – PubMed.
Resources
Free Webinar Video: Watch CMTA’s July 2023 Quarterly Lunch & Learn webinar announcing the findings of the 2022 review and the updated neurotoxic drug list.
Should Individuals With CMT Avoid These Drugs?
CMTA does not make any recommendations for or against any medication. Medication decisions should be made in consultation with a qualified healthcare provider.
Which Questions Should I Ask if My Doctor Wants to Prescribe These Drugs?
If you have concerns about a medication your healthcare provider recommends, discuss them, ask about alternative options, and follow their guidance.
Is CMTA’s Original Neurotoxic Drug List Still Available?
CMTA revised its Neurotoxic Drug List in July 2023, retaining only Vincristine and Paclitaxel. The original list is no longer available.
Key Considerations
Understanding the potential risks of neurotoxic medications is an essential part of effectively managing CMT. While individuals can experience side effects from any medication, evidence-based science shows that CMT does not appear to increase the potential risk for side effects except for Vincristine and Paclitaxel.
Side effects and responses to any medication can differ from person to person. Medication decisions should be between you and your healthcare provider. Please speak with a qualified healthcare provider about any concerns or questions and follow their guidance.
Stay Empowered with Expert Care
Understanding potential medication risks is an important part of managing CMT. While Vincristine and Paclitaxel have been identified as neurotoxic concerns, medication decisions should always be made in consultation with a qualified healthcare provider.
CMTA is committed to providing the CMT community with the latest evidence-based information. Visit our CMTA Center of Excellence directory to find expert care from specialists who understand the complexities of CMT.
