Serene Forest

Wednesday, August 26, 2015

The Truth About The “New” Drug For Periodic Paralysis: It Is Not New

The Truth About The “New” Drug For Periodic Paralysis: 

It Is Not New And It Is Not For Everyone


A member of our Periodic Paralysis Network Support, Education, Advocacy Group asked me today for my personal opinion of the new drug approved by the FDA, which is now available to treat Periodic Paralysis. I myself have received no fewer than fifty Google alerts about this new wonder drug touted to treat Hypokalemic Periodic Paralysis and Hyperkalemic Periodic Paralysis. I have seen no articles discussing the truth about this drug in relationship to what Periodic Paralysis really is and how the paralysis and other symptoms in individuals are created with this condition. My reply is as follows addressing these issues.

I want to begin by saying we at PPN are a patient advocacy group as well as a support group and educational group. It is our desire and duty to provide information to keep each of our members informed, safe and to be the "best each person can be." For that reason I am passing along this information.

Periodic Paralysis is a mineral metabolic disorder (ion channelopathy). Until this “new” drug, there were NO drugs recommended or approved by the FDA for the treatment of Periodic Paralysis. The ones typically used, diamox/acetazolamide, are strictly "off-label" (made and used for other conditions). These drugs were and are unsafe for most individuals with Periodic Paralysis due to serious, sometimes harmful side effects, short term and long term. They are carbonic anhydrase inhibitors and are sulfa-based diuretics.

The “new” drug, now approved by the FDA to treat Periodic Paralysis, dichlorphen-amide, which will also be known as keveyis, is basically another carbonic anhydrase inhibitor (a diuretic) and it is sulfa-based. It is exactly the same as diamox (acetazolamide) so if someone has a problem with those drugs they most likely cannot take the new drug.

Regarding the condition of Periodic Paralysis itself, some things need to be explained in order to understand how this drug may or may not work. There are several forms of Periodic Paralysis and many genetic mutations for each form. The different types cause the paralytic episodes, muscle weakness and other symptoms in varying ways. Potassium shifts in the body abnormally either in low, high or within normal ranges caused by many triggers. This happens as follows depending on the various forms.
  • Paralysis results from potassium moving from the blood into muscle cells in an abnormal way,
  • Paralysis results from problems with the way the body controls sodium and potassium levels in cells.
  • Paralysis results when the channel does not open properly and potassium cannot leave the cell.
  • Paralysis results when potassium shifts within normal ranges.
  • The sodium channels close much too slowly and the sodium, potassium, chloride and water continue to flow into the muscles.
  • Or the normal pores in the muscle cell walls just do not work correctly.
Knowing this information, my question is as follows, “How can one drug possibly treat and correct all of these possible malfunctions?”

Another serious issue is related to the lack of knowledge that many individuals with Periodic Paralysis must deal with regarding the diagnosis of the condition.

More than one half of all of the individuals with the various forms of Periodic Paralysis will not know what mutation they have due to poor, limited, narrow or biased DNA/genetic testing or because many of the mutations have yet to be discovered and research in this area has been halted. Without knowledge of which form a person has, taking these drugs is very risky.

Now I will discuss what this drug entails’

What is a carbonic anhydrase inhibitor?

A carbonic anhydrase inhibitor is a diuretic. It works by causing “increased excretion of bicarbonate with accompanying sodium, potassium and water, resulting in an increased flow of alkaline urine. They inhibit transport of bicarbonate into the interstitium from the proximal convoluted tubule. Therefore less sodium is reabsorbed, causing greater sodium, bicarbonate and water loss in the urine.”

From the pharmaceutical company itself about dichlorphenamide/keveyis:

Keveyis is not for everyone. Do not take Keveyis if you:

Are on a high-dose aspirin regimen
Are allergic to sulfa-based drugs
Have liver, kidney, or certain lung conditions
Are pregnant, planning to become pregnant, or nursing
Are under 18 years old”

“Taking Keveyis may cause a drop in the amount of potassium (an electrolyte) in your body, which can lead to heart problems. Ask your doctor if you need to eat foods that contain high amounts of potassium while taking Keveyis.” (This means it creates Hypokalemia (low potassium levels), exactly the reason most people are taking it.)

Your body may produce too much acid or may not be able to remove enough acid from body fluids while taking Keveyis. Your doctor will run tests on a regular basis to check for signs of acid buildup and may reduce your dose or stop your treatment with Keveyis.” (This means it can cause the development of metabolic acidosis, which nearly everyone with a form of Periodic Paralysis is prone to and develops due to the nature of Periodic Paralysis. It is a mineral metabolic disorder.)

”Keveyis may also increase the risk of falls, especially in elderly patients and patients taking high doses of Keveyis. Use caution when driving, operating machinery, or performing any other hazardous activities while taking Keveyis, as this medication may cause drowsiness.” (Most individuals with Periodic Paralysis already have issues with balance, weakness and possibly falling.)

Unfortunately, these are some of the same issues as diamox/acetazolamide!

I personally cannot take it... keveyis is sulfa based (I cannot take sulfa-based drugs) and diamox/acetazolamide nearly killed me for that reason and others.

Even for individuals who take diamox/acetazolamide and it helps them reduce episodes, most still have symptoms, and side effects; both short term and long term. These effects can be very serious and even deadly. It can cause liver disease and kidney stones as well as metabolic acidosis, very serious conditions.

In my personal opinion, I do not suggest that anyone take either of them. That being said, however, some people do fairly well but not without new problems. This is something each person must decide for himself or herself. One will not know unless he or she tries it. But like I said, some of the effects are over time and at quite a cost.

 One of our members developed kidney stones, and then had to have surgery and it nearly killed her due to the anesthesia and other issues. She cannot do it again and they did not get all of the stones. She is in constant pain and will never be as well as he was before taking the drug.

I am so sorry to be so biased...but I want everyone to be safe...and I do not believe these drugs to be safe for anyone of us with Periodic Paralysis.

The truth is that dichlorphenamide, which will also be known as keveyis, is another carbonic anhydrase inhibitor, a diuretic that is a sulfa-based drug. It is the same as diamox/acetazolamide; it is nothing new or different. It is just more of the same.

But to be fair, some people do well on these medications and we are not telling anyone to stop taking them if that is the case.

I did find this in one study:
“It was determined that some individuals became who became unresponsive or worsened by acetazolamide, responded favorably to dichlorphenamide.”

However, as previously discussed, others do not do well and/or they may develop side effects from these drugs, which can be harmful and can become life threatening. If that is the case, there is more information here for you to consider. If you have been given a prescription for one of them, you may want to read the information here before you start it, so you will know what to expect or what to look for, in order to be safe.

I hope this is helpful and if you decide to take it please do so carefully and monitor yourself very closely.

I have included many links to articles and studies regarding these drugs:

The following is information about the side effects of dichlorphenamide (keveyis):’s-Keveyis™-dichlorphenamide-50-mg#.VdZBTvRS6ih

The following is some information about diamox/acetazolamide use in individuals with Periodic Paralysis:

For those with Periodic Paralysis, some forms of Hypokalemic Periodic Paralysis do not respond to diamox/acetazolamide and some cause paralysis and/or worse symptoms:

 A study from 2001 relates two different types in particular but I am sure more have been discovered by now: CACNL1A3=Hypokalemic Periodic Paralysis-1 and SCN4A=
Hypokalemic Periodic Paralysis-2, each with several mutations...and of course there are the ones that have not been found yet.

When someone is diagnosed with Hypokalemic Periodic Paralysis, clinically, (based on their symptoms); one must be very careful. One form does not respond to diamox/acetazolamide, and it causes more paralysis or more serious symptoms. So, diamox/acetazolamide should not automatically be given to people clinically diagnosed with Hypokalemic Periodic Paralysis or if it is, it should be used with extreme caution.

From the study:

“In conclusion the present study demonstrates that genetic characterization of HypoPP patients is important to decipher the clinical and histopathological features of the disease, and to predict the response to therapy. We suggest that mutations in the SCN4A gene should be systematically sought in HypoPP patients suffering from paralytic attacks followed by myalgias or worsened by acetazolamide, and when muscle biopsies reveal the presence of tubular aggregates.”

As written above, about half of us do not have a genetic diagnosis and do not know what form of Periodic Paralysis we actually have. If we are going to take these medications, we must be very careful and closely monitor our symptoms and the side effects.

Connection between liver disease and carbonic anhydrase inhibitors:

It has been linked to liver disease ranging from acute hepatitis to severe injury with acute liver failure or prolonged jaundice.

Articles and information about issues related to acetazolamide and diamox. 

Contraindications for oral diamox

More information about diamox:

Side effects for children:

Some things to consider before putting your child on diamox/acetazolamide: Many people do fine on it but there can be some serious side effects to watch for including kidney stones, liver dysfunction, osteoporosis and metabolic acidosis. It should not to be used for children under 12 because it can affect growth. It is a sulfa drug...some people cannot take sulfa drugs.

"This medication should not be used in children less than 12 because it may affect normal growth."

I understand that in some cases it may be the best of two evils...a very tough decision...but you must be aware of the possibilities...

Acetazolamide and Kidney Stones 

Carbonic anhydrase inhibitors and the Eyes: 

Carbonic anhydrase inhibitors (CAIs) reduce eye pressure by decreasing the production of intraocular fluid.

...systemic CAIs possess undesired side effects such as numbness and tingling of extremities; metallic taste; depression; fatigue; malaise; weight loss; decreased libido; gastrointestinal irritation; metabolic acidosis; renal calculi (kidney stones) and transient myopia.

Myopia, also known as near-sightedness and short-sightedness, is a condition of the eye where the light that comes in does not directly focus on the retina but in front of it, causing the image that one sees when looking at a distant object to be out of focus, but in focus when looking at a close object.
(The myopia comes and goes causing dizziness, etc...)

Transient myopia is a side effect of sulfa drugs:

PPN Blog Articles written about the effects of drugs/medications/pharmaceuticals/anesthesia in Periodic Paralysis

Until later...

Monday, August 10, 2015

A New Drug For Periodic Paralysis? Helpful Or More Of The Same?

Hello All,

There is a big announcement in the world of Periodic Paralysis today!! A drug has been approved by the FDA as the first drug to treat Periodic Paralysis. It is Dichlorphenamide also known as Keveyis. It is a carbonic anhydrase inhibitors (a diuretic) and it is sulfa-based. It is not new to PP and has been used before but was pulled from the market while studies were done over a period of twenty-three years.

Until now a few other drugs have been used but they are all 'off-label' drugs. This means they were created for other conditions. They are forms of diuretics. They work for some people depending on the particular genetic mutation an individual has. They are not without side effects, both short term and long term. For some they can be very harmful, especially if one has an allergy or intolerance to sulfa-based drugs or the wrong genetic mutation.

This announcement is good for some lucky people and just "more of the same" for others of us who cannot tolerate the carbonic anhydrase inhibitors which are sulfa-based.

This drug,
Dichlorphenamide, needs to be used with great care, just as the off-label drugs.

It is nice to see research for treatments of Periodic Paralysis, but it would be nice to see research being done for those of us who cannot handle these drugs. It would be nice to see research outside of the proverbial box for Periodic Paralysis.