Medicine & Research

Examining the Ampyra™ Experience

By Daniel Kantor, M.D.

On Jan. 22, 2010, the U.S. Food and Drug Administration approved Ampyra (dalfampridine) as a treatment for walking impairment in multiple sclerosis. Since that time, many people who have tried Ampyra have had follow-up questions about the medication, its efficacy, dosage, and whether or not certain health changes are related to usage.

Before addressing those questions, let’s review some basic information about Ampyra. It’s important to understand that Ampyra is not a disease-modifying drug. A disease-modifying drug prevents new attacks, while symptomatic treatments help to minimize the effects of symptoms that are already there. So, if you have no trouble walking, you take a disease-modifying drug to prevent a MS flare-up from making you unstable or weak in your legs. Ampyra, on the other hand, is supposed to help you walk better if you already have trouble walking.

A Great Enabler

This is why I call Ampyra a “neurofunctional enabler” – it enables you to function better neurologically. Although it is approved for walking problems in MS, we know that it helps with so many other symptoms. Your doctor might use Ampyra off-label to improve MS symptoms, such as fatigue, spasticity (muscle tightness), and visual fluctuations.

I have used it to help my patients with a multitude of symptoms, including nerve pain. I find that initially the pain, such as the shooting pains in the mouth of trigeminal neuralgia, gets a little worse (probably because the electrical signal is working better), but then as the nerve works more normally, the pain improves.

The argument is that it doesn't simply cover up symptoms by making you feel better, it actually makes you function better because of its mechanism of action, which enhances the electrical conduction down a nerve that allows us to do everything from walk to speak to think. 

So, although the company that sells Ampyra, Acorda Therapeutics, Inc., is permitted only to advertise benefits related to walking, other improvements you feel may indeed be related to the medication.

Potential negative effects should also be considered. These have been documented in clinical trials.

Side Effects

Ampyra prolongs the electrical signal in the axons (nerves); this is how it enables people with MS to walk and function better. But we also know that too much electricity in the brain causes a seizure, making it the most concerning potential side effect of Ampyra.

It is unclear whether the FDA-approved dose (10 mg by mouth every 12 hours) increases the risk, or whether it takes a higher dose to increase the risk. This is why it is so important not to pop extra pills in search of a greater effect. It is also the reason people with a history of seizures should not take the medication.

Some medications go through the kidneys and others through the liver; Ampyra goes through the kidneys. As a result, people with reduced kidney function may not clear the medication from their body and it will build up. This is like taking too much of the medicine, increasing the risk for seizures.

Clinical trials record every problem a participant has written down. There seemed to be more urinary tract infections (UTIs) in those receiving Ampyra as compared to those receiving a placebo; this observation is curious because it is initially unclear why Ampyra should do that.

Since only people who had urinary tract complaints, such as painful urination, underwent urine testing for bacteria, it is possible that those taking Ampyra simply had better sensation because the nerves were working better. Therefore they noticed that they had the infections, while other people who were on placebo may have had no improvement in their sensation and so they didn’t even know that they had an infection. (In general, many UTIs go unnoticed.) Of course, we don’t know this for sure and there could be an actual reason why Ampyra increases the risk for UTIs.

What Else Might Happen

Different people have noticed other potential reactions from Ampyra. Since it has not been around for very long, it is unclear whether these side effects are truly as a result of the medication, or whether they happened by chance in a person who happened to be taking the medication. Only time will tell.

On a brighter note, one person noticed that her hair seemed to grow better after starting Ampyra. This sounds curious and may turn out not to be from the Ampyra. There is some scientific evidence that drugs such as Rogaine® (Minoxidil) help with hair growth by opening and not closing potassium channels. Ampyra acts as a potassium channel blocker – so it would seem that, if anything, the opposite should be true. 

I had a patient with two years of intractable eructation (belching or burping) that resolved five days after starting 4-aminopyridine (a compounded version of the chemical in Ampyra). This probably worked because the medication reduced the tightness in the throat muscles which was likely causing the eructation. 

When You Will Know

The nice thing about Ampyra is that you know usually within six to eight weeks if it is helping you or not. If it is helping you, you will probably choose to continue it, but if you haven't noticed a change in that period of time, then you will probably look for other (hopefully future) treatments. This is unlike the disease-modifying drugs where we say, “you won't necessarily feel any different and you won't know if it is helping you, but you should continue to take it because you may have been worse off without it.” 

Remember Ampyra is an “enabler” and not a “replacer.” If you are on a disease-modifying medication, stay on it as you add Ampyra to your treatment regimen.

How Ampyra Works

First, let’s take a look at how nerves work. Nerves work through electrical signaling; this is called an action potential. Sodium channels open up, allowing sodium ions (molecules) to enter through the cell membrane into the axon (the wire of the nerve); this creates depolarization, a positive charge inside the neuron. 

Then, potassium channels open up to allow potassium ions to exit the axon; since potassium ions also have a positive charge, this repolarization returns the neuron to an overall negative charge (close to baseline.) There is a wave of these channels opening and closing down the length of the axon, causing an electrical signal with the eventual release of neurotransmitters (molecules like dopamine and serotonin), which in turn cause the next nerve to send electrical signals. 

Axons that have lost some of their myelin cover because of MS have trouble seeping out their potassium ions. 

Ampyra (dalfampridine) is a potassium channel blocker (antagonist), and if the potassium ions have trouble seeping out of the axon, the action potential is prolonged and conduction through the nerve is improved. Improved nerve conduction enables better nerve functioning. Ampyra doesn’t change the structure of the nerve, but it does allow it to work better. 

How to Get Ampyra 

Before the FDA approved Ampyra (dalfampridine) at the beginning of 2010, the only way of getting it was through one of the clinical trials. Now many insurance companies are putting it on their formularies, but often a prior authorization is needed. So, if you are curious about whether Ampyra can complement your MS regimen, speak to your neurologist

If you and your neurologist decide that it is worth a try, you must sign a special form that allows your neurologist to send in a request for a reimbursement team to start working with your insurance. It will also be determined which specialty pharmacy is going to send the medication to you. Ampyra is only available through mail-order pharmacies and not through your local retail pharmacy.

Next, the specialty pharmacy may ask your neurologist to fill out a prior authorization request form. If everything goes smoothly, your specialty pharmacy will call you to arrange delivery. 

Ampyra Patient Support Services can tell you if you are eligible for their co-pay mitigation program. If eligible, people with private insurance may not pay more than $40 per month for their prescription (where allowed by law). If you don’t have insurance and you meet certain requirements you may qualify to receive Ampyra at no cost. For more information call 888-881-1918 Monday through Friday from 8 a.m. to 8 p.m. ET.

What are other people who cannot get Ampyra doing?

Prior to Ampyra being FDA approved, some people were taking compounded 4-aminopyridine. A compounded medication is mixed by a pharmacist, as opposed to arriving as a packaged pill from a factory. People in the U.S. are moving away from using the compounded version because it is shorter acting and may have more side effects (such as gastrointestinal upset). There is also a potential for compounding errors and incorrect dosages.

Daniel Kantor, M.D., is the President of the Florida Society of Neurology, the Medical Director of Neurologique and a MS and Migraine specialist in Ponte Vedra, FL.

(Last reviewed 11/2010)