Peter D. Donofrio, M.D. is professor of Neurology and director of the Neuromuscular Division of the Department of Neurology at Vanderbilt University Medical Center. He is director of Neuropathy Center at Vanderbilt.
Read the excellent article by Dr. Donofrio on Medication Induced Neuropathy that is printed below. The limits of the blood-brain and blood nerve barriers are known through research in many disease processes and the influence of genetics or metabolic factors in the vulnerability of some patients to certain disease conditions. The concept of the blood brain and blood nerve barriers have been misused by expert neurologists to acknowledge medication induced neuropathy while denying that toxic herbicides cause neuropathy whether it be Agent Orange (Vietnam War) or other toxins manufactured by chemical companies. Why?
However, in recent articles in the Journal of the Peripheral Nervous System, it is noted that the blood brain and blood nerve barriers do not work perfectly and often does not prevent damage to the peripheral nerves or even the brain as originally thought. The fact noted by Dr. Norman Latov in his book for patients, genetic factors play an important role in a patients susceptibility to certain neuropathies.
Here is Dr. Donofrio, article:
Medication-Induced Neuropathy
By Peter D. Donofrio, M.D.
You’ve undoubtedly heard the old saying, “It’s what you don’t know that can hurt you.” When it comes to neuropathy, there may be something your doctors don’t know that can hurt you as well.
Renowned New York Times health columnist Jane Brody recently shared with readers of her column that she experienced a bout of peripheral neuropathy several decades ago when a misplaced shot of morphine damaged a sensory nerve in her thigh. Obviously, her doctor never intended for that to happen. Fortunately, the nerve recovered in three years, but for much of that time, Brody couldn’t even tolerate something brushing against her leg.¹ Brody’s peripheral neuropathy can be categorized as an “iatrogenic” case—that is, a condition that is actually caused by medical care.
Iatrogenic causes for peripheral neuropathy aren’t always as blatant as a misplaced shot. In fact, peripheral neuropathy can be caused by nerve toxicity from commonly prescribed drugs: medications prescribed by physicians who are not aware of the possible relationship between the medication and the neuropathy. Why aren’t they aware? After all, aren’t these the experts you trust with your health, your well-being…your life?
Your doctors are well aware of the medications they are prescribing, but the fact is they may not be aware of medications other physicians have prescribed, nor are they aware of every uncommon adverse reaction of a medication. Many medications have hundreds of reported side effects. Often primary care physicians are inundated by a waiting room full of very ill patients requiring immediate care and don’t have time to fully review in detail every note or test result they receive.
Simply put, your specialists and primary physicians need your help. If you have a neuropathy and are concerned it may arise from a medication, speak up. Some medications and interactions between drugs can cause complications and even irreversible conditions. For example, thalidomide has proven to be very effective for treating skin diseases and some kinds of cancer. In fact, thalidomide has experienced a resurgence of use in the medical community for its effectiveness against several dermatological conditions. The occurrence of neuropathy, however, has also been tied to thalidomide. It is not typically related to the daily dose of the drug nor the duration of treatment; it’s more commonly found in patients who are slow drug acetylators—in other words, those patients whose bodies take longer to metabolize certain drugs.
The good news is that when patients with neuropathy stop using thalidomide, 25 percent of them recover completely, and 30 percent improve partially. What’s not so comforting is the fact that 45 percent of reported cases do not recover at all.² This example illustrates the need for you to consult with your physician if you take any of the medications associated with causing neuropathy. It is important to remember that you are not expected to be a medical expert, however, you are expected to know the names of the medications you’re taking, how long you have been taking them, and to be able to describe them to every doctor you visit. Thus, you need to assume the role of being your own patient advocate. Today’s health care system is complicated, and as such, you need to be able to provide to your doctor and to other health care providers as much information about your treatments as possible. Communication of your medications and duration of use is critical for your primary care and specialist physicians to offer you excellence in care.
Take the first step by reviewing the list of medications below that can induce neuropathy and let your physicians know if you are taking any of them. Remember to tell your physicians that you are not questioning their judgment; just asking them to review the medications in the context of your neuropathy. More often than not, they will welcome this active role in your treatment and see this as an opportunity to better educate themselves. Not only will you be helping yourself, but you could be helping others as well. Also, keep in mind that these medication do not always cause neuropathy, and it is the unique metabolism of certain patients that may cause them to develop neuropathy when prescribed a certain drug.
The following is a list of drugs that can cause neuropathy in certain patients:
| Allopurinol Amiodarone Ara-C Carboplatin Cisplatin Colchicine Danosine (ddl) Dapsone Disulfiram Docetaxel Etoposide (VP-16) Ethambutol Etoposide Gentamin Gold Indomethacin Isoniazid Lithium L-tryptophan contaminant |
Mercury Metronidazole Misonidazole Nitrofurantoin Nitrous Oxide Paclitaxel Perhexilene Phenytoin Pyridoxine Sulfapyridine Statins Stavudine (d4T) Streptokinase Suramin Tacrolimus Thalidomide TNF-alpha antagonists Tumor Necrosis Factor Vincristine Zalcitabine (ddC) Zimeldine |
The peripheral nerves are protected by a blood-nerve barrier and might be perceived to be at a lessened risk than other organs for toxicity. Certain patients, however, may be at a higher risk for developing peripheral nerve toxicity due to genetic or metabolic factors. Many therapies have toxicities that must be tolerated because the treatments are necessary, such as treatments for HIV and malignancy. Developing additional therapies to prevent and/or ameliorate the toxic neuropathy associated with certain medications is an important area of research and clinical trials are on-going.
2015 UPDATE: Reports from the FDA information on Fluoroquinolone has noted significant instances of chronic peripheral neuropathy. Military doctors wrote 1.2 million scripts for this drug during the Gulf War and many believe that it is the cause of the Gulf War Syndrome or Fluoroquinolone Toxicity Syndrome.
1 Brody, Jane. “The Many Ills of Peripheral Nerve Damage.” The New York Times, October 20, 2009.
2 Zimmer, Carl. “Answers Begin to Emerge on How Thalidomide Caused Defects.” The New York Times, March 16, 2010.
In 2006, Dr. Donofrio accepted the position of Chief of the Neuromuscular Section in the Department of Neurology at Vanderbilt University. In addition, he is the Head of the Muscular Dystrophy Association Clinic, the ALS Clinic, and is the Director of the EMG Lab. He is presently on the Board of Directors of the American Academy of Neuromuscular and Electrodiagnostic Medicine (AANEM) and serves on the Medical Economics and Management Committee of the American Academy of Neurology.
See: Textbook of Peripheral Neuropathy, Peter D Donofrio, MD, Editor, Professor of Neuropathy, Chief of Neuromuscular Section, Vanderbilt University Medical Center, Nashville, TN Published by DEMOS Medical, 2012.
Five years ago I was prescribed Ofloxacin, a fluoroquinolone (FQ) antibiotic to treat a MRSA virus infection following a joint replacement surgery. I took 41 doses of 400 mgs. My feet began burning shortly after taking the drug. I told my VA doctor about the connection. He dismissed it and instead tested me for diabetes and assumed it to be in my head (somatic). Eventually I convinced a VA doctor that there may be a connection after I convinced her to look at the FDA website and see the Safety Alert on fluoroquinolones. Eventually I was given an EMG/NCS and the old neurologist wrote in his report that I did not have a PN. That was in Jan 2013. It has taken me until last week to convince another VA doctor to give me a consultation by another doctor after educating him about the differences between LFN and SFN. Add fluoroquinolones to the list in this article. The Air Force Times reported last year that military Docs/PAs wrote 1.2 million prescriptions between 2009-2012. Many docs and researchers believe that Gulf War Syndrome is actually Fluoroquinolone Toxicity Syndrome. The symptoms are identical. Thanks for the great articles.
Mark: I will add Fluoroquinolone to our articles. For the record, the EMG and NCS do not rule out neuropathy as there is NO test that does this for a patient. The only POSSIBLE exception is the skin biopsy for SFN which will confirm damage and MAY rule out SFN. Many of the SFN’s are immune mediated and if so can be treated with IVIg. Otherwise, all these tests do is note if there has been damage to the nerves and the extent of damage… Ignorance spreads faster than fact even among the intelligent. And you are welcome. I will send you an e mail with other information.
Col Richardson: Thank you for adding fluoroquinolones to the list. This class of drug is responsible for many other adverse drug effects to include tendon problems (FDA Black Box warning), CNS problems, mitochondria toxicity, etc. It is a very big issue for many people, myself included. There are two websites that have lots of information and links: http://www.floxiehope.com and myquinstory.info. Also, I would like to correct your posting of the fluoroquinolones to this article. The 1.2 million prescriptions was given in 2009-2011. During the Gulf War, Cipro (a FQ) was given out to the Soldiers and Marines as a preventative measure against anthrax. See the Airforce Times 2013 article “New FDA warnings on Cipro may tie into Gulf War illness”.
And lastly, fluoroquinolones have been used as chemotherapy or as an adjunct to existing chemotherapy because of there apoptotic properties. For a quick summary of Fluoroquinolone Toxicity Syndrome and a list of medical research, query, Dr. Miriam J. de Jonge’s “Dear Colleague” letter. I believe there is a link to it on the myquinstory.info site.
Thank you for your dedication in educating people about neuropathy. I served in the Army with Vietnam veterans who were suffering from the effects of Agent Orange. It is devastating.
May GOD bless you and your efforts on this website.
I was treated with Bactrim for an ear infection (primary care Doc thought it best due to my A Fib status). All hell broke loose and my blood went south (liver, etc) It came back in 2-3 wees with further testing , but then I was notified that I had a positive reading for ANA. Since that time I developed many Lupus, Sjorgren’s type symptoms including burning feet. It is now October and the burning has intensified. The recent blood work indicated negative for those diseases and other autoimmune antibodies. But, my recent EMG testing from a neurologist indicated SFN. I am now on 25mg Lyrica twice daily with some relief.
Terry: Small Fiber Neuropathy is confirmed with a simple skin biopsy. See the article on skin biopsy on the website for small fiber neuropathy and speak to the doctor as this needs to be confirmed. Second many SFN’s are immune mediated and can be treated with IVIg. Please see these two links and speak to the doctor if this might be true in your case as it would seem that something in your history notes that your immune system is involved. Small Fiber Neuropathy see: http://neuropathyjournal.org/small-fiber-neuropathy/ Skin Biopsy see: http://neuropathyjournal.org/skin-biopsy/ and IVIG http://neuropathyjournal.org/category/why-ivig/
You might want to look into that lyrica. I was on it and had horrible side effects. I also read it caused tumors in mice but not rats, unknown what it does to the human body. Also had bad withdrawals. I was also posioned by cipro & leva, still recovering been almost a yr.
Brenda: Yes Lyrica and many of the drugs have POSSIBLE side effects yet some people do fine on it and it reduces the neuropathic pain for them. All drugs must be used with caution and if side effects are worse than the symptoms then other options need to be explored. Our bodies for a number of reasons are different and how we react to drugs is a very personal fact. I remember when I was put on one of the seizure drugs and began to talk backwards or could not put a sentence together. Not fun… but of course we stopped it yet I did well on Nortriptyline which also helped me sleep while taking away 85% of my pain. Working with the doctor who has some training in the issues of drugs is very important for neuropathy patients until they find what works for them and this may be a nondrug option such as biofeedback or a topical compound as mentioned in the article.
All the uproar about Lyrica can be found on the askapatient website, which put fear in me while I was on that drug, yet I felt none of the symptoms except small orgasm. I was up to 300mg a day and felt I could do better not taking it. That was a big mistake as I have the worst neuropathy pain now that is totally uncontrolled. I cannot go back to Lyrica as I lost my insurance so I have asked my VA doc to try Cymbalta as my neuropathy is currently very progressive.
Evan: I had difficulty with all the drugs with serious side effects…. the one that helped me was Nortriptyline and it is an old drug of the same class as Cymbalta so the VA may give it. If taken at night as they work you up to the recommended dosage of 75 mg it also helps you sleep. Will send more information from our e mail address.
I’ve been suffering with issues since taking Cipro 4 years ago and have been diagnosed with mild peripheral neuropathy among a few other things. I’m not sure how they decide its mild as it keeps me immobile and many sleepless nights due to pain. I’ve been seeing a wellness chiropractor 3 days a week for 4 months now and it has helped somewhat, but my PCP dumped me for not following her prescription regiment which included pain and antidepressant meds that I did not want to take. What type of doctor can do a puncture test for SFN? I would really prefer to not have to go back to a new PCP as after 4 attempts they all deny fluoroquinolones could have caused the damage and they all want to give me another medication to mask the problem. Any help or advice would be appreciated.
Traci: Here is the warning from https://www.nlm.nih.gov/medlineplus/druginfo/meds/a688016.html : Ciprofloxacin may cause nerve damage that may not go away even after you stop taking ciprofloxacin. This damage may occur soon after you begin taking ciprofloxacin. If you experience any of the following symptoms, call your doctor immediately: numbness, tingling, pain, or burning in the arms or legs; or a change in your ability to feel light touch, pain, heat, or cold. If you experience these symptoms, do not take any more ciprofloxacin until you talk to your doctor. Your doctor may prescribe a different antibiotic for you to take instead of ciprofloxacin. Ciprofloxacin may cause other side effects. Call your doctor if you have any unusual problems while taking this medication. If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online [at http://www.fda.gov/Safety/MedWatch%5D or by phone [1-800-332-1088].
In the Textbook of Peripheral Neuropathy by Peter Donofrio Professor of Neurology, Chief Neuromuscular Section, Vanderbilt University Medical Center Nashville published 2012 by DEMOS Medical, he states on page 205 that Fluoroquinolone absolutely DOES CAUSE a polyneuropathy but unlike the National Institute of Health, notes that ‘patients typically recover within 2 weeks when the medication is stopped”. I would assume that some patients are not ‘typical’ when it comes to such recovery which we know is true from any types of neuropathy!
I will send you a separate E Mail in regards to these issues and other information.
Hi,
I have terrible nerve pain and muscle atrophy in my arms and a bit in my legs with burning feeling in my arms and hands and knees especially the inner part of my knees. I have RA and celiac and was wondering if you think this pain is related to that or perhaps to the fact that i took Humira again straight after i finished 4 months of breastfeeding as that is when my arms started to atrophy. ?
Carol: You need to be evaluated by a Hematologist and a Neuromuscular Neurologist. Celiac disease is a known cause of Peripheral Neuropathy according to Dr. Latov PhD MD of Weill Medical College of Cornell University but it would be more likely that the Drug Humira is causing many of these symptoms especially the muscle wasting and other symptoms. Please see a Hematologist or other related specialist ASAP and then follow up with an evaluation by a Neuromuscular Neurologist.
I would like to add that physicians are not aware of these issues. I found out too late. Unless you r fortunate to see a very informed neurologist, these devastating adverse effects will never b recognized or reported which leads to a vast under reporting of events.
CW: Physician training and education is one of the MOST critical areas in the field of Peripheral Neuropathy. We have come a long way in this regard. I will send you some information on resources that may help you by separate E mail. Col Gene
I have a diagnosis of SFN having 1.8 small working fibres to the mm when it should be between 5 and 8. The only thing tests revealed was B6 toxicity. Having stopped taking B6 for approx 8 months my levels have returned to the high end of normal.
I have all the usual SFN symptoms but they are manageable. What plagues me is terrible itching. starting as soon as I get up in the morning. It can go on for hours, is mostly in my arms and legs and is triggered by change of temperature. I can’t shower in the mornings, have to heat my clothes to try and maintain my temperature.The temperature yesterday here was 30 degrees and i had a swim in a friends pool which was also at a very warm temperature. However, that started and itching attack which went on for about an hour until my body temperature got back to normal. I also frequently have mega sweats Any exertion causes these and I never feel comfortable!
I am 65 , have had the sweats for 17 years which I put down to menopause and have had the itching for 7 years.
I was at one point put on HRT as they thought the sweats and itching were caused by a hormone imbalance.
After 11 months I was diagnosed with oestrogen receptive breast cancer so of course came off the HRT. Two operations , (Nov and Dec 2015) They also inserted a Mirena coil (progesterone) for 7 months and my SFN symptoms escalated dramatically causing major icy sensations. I spent the whole time swathed in blankets to feel tolerably warm.! I begged to have the Mirena coil removed and things improved re the iciness.
Can SFN be caused by hormone imbalance ? If the B6 toxicity was the main cause for my SFN is there a chance that my small fibre nerves can repair? Are these extreme itching and sweating bouts normal for SFN? My neurologist has now referred me to an immunologist as my itching went away for short while when I was ill with a sickness bug and didn’t eat for 4 days.
However, the itching feels like an allergy to the cold although I don’t get any hives etc. if it was a food allergy I’m thinking I would get the effects at varying times depending on my diet. could it just be the effects of the temperature on my damaged nerves?
I’m so exhausted with all this and desperate to find some solution without resorting to taking Lyrica as I have two friend who’ve tried it and both had extremely adverse effects.
Any help would be greatly appreciated.
Helen: I will reply directly by E mail to you. Gene