Nuedexta,has it helped anyone
 

I usually don't take new drugs but since this one contains two generic drugs that have been around for a while I thought I would give it a shot. My neurologist and pain management doctors have been pushing it for a couple of months.

Has anyone been on Nuedexta long enough to report it effects? Any side effects, (other than the cost of going broke because treatment for a year costs $4,500 to $5,000) My neurologist believes that I will have some time before my insurance company figures out that I am using it off label.

For anyone who cannot take it because of the cost I asked my neurologist if he could have it compounded for me since both of the component drugs are generics and he replied, "great idea."

Any feed back would be very appreciated!

You will want to be screened for long QT syndrome and avoid drugs which are additive with it. (like methadone and Elavil).

http://www.drugs.com/nuedexta.html

I am new to RSD so I am looking at all things to help with this maddening disease. Are they going to compound this into a liquid or a cream?

I've been on it for a couple of months and it's been pretty good. Not only does the quinidine sulfate completely block the metabolism of the dextromethorphan - so a little goes a long way - but it clearly potentates my Namenda (memantine HCl)) as well. That, and with any NDMA receptor antagonist, the dextromethorphan will also potentate opioids, at least to some extent. (See prior threads on dextromethorphan).

That said, mrsD is absolutely correct, no one should use the stuff if they have a "long Q - T interval." And although this is something that is more likely to be "honored in the breech," that means having a EKG first. No exceptions.

Mike

I would not think this combo product would work topically.

The quinidine has to be absorbed and go to the liver to extend the effects of the DM.

This is a link explaining the actions of quinidine to block metabolism of DM in the liver:
http://www.drugs.com/interactions-ch...t=844-0,1981-0

The link I gave earlier in this thread, also lists other drugs affected by quinidine. Quinidine at one time was a common drug for the treatment of arrhythmias of the heart. Because it interacts with so many other drugs as illustrated here, it has fallen into disuse.

This link from drug checker at drugs.com lists them all, and you can see that this new drug combo should be treated with care and respect because of it.
http://www.drugs.com/drug-interactions/quinidine.html
http://www.drugs.com/drug-interactio...&generic_only=

mrsD -

If I may, the last two links in your post - actually they appear to be the same, from www.Drugs.com - strike me as somewhat alarmist. Specifically, I set my search so that it produced a list of "Medications known to interact with quinidine," and got 135 hits for each of the two links. But then randomly sampling maybe 20 drugs, the same operative language is repeated over and over:

Theoretically, co administration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s). Clinically significant prolongation of QT interval and hypokalemia occur infrequently when beta-2 adrenergic agonists are inhaled at normally recommended dosages. However, these effects may be more common when the drugs are administered systemically or when recommended dosages are exceeded. [Emphasis added.]

So to begin with, the list of "Medications known to interact with quinidine" is, with respect to a large number of the drugs listed, is seemingly modified by "theoretically." (Interesting use of "known.") That, and while "the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable," "the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved," whatever that means.

Then it is suggested that those at greatest risk have preexisting conditions that would - with the catch all exception of generic "cardiac disease" - would be picked up by the EKG that we both agree should be mandatory before Nuedexta is used. And as to generic "cardiac disease," I raised that issue a couple of months ago with my cardiologist, where I had a non-transmural MI in 2004 due to a 100% (and chronic by the time it was spotted) occlusion of the mid-LAD, resulting in a 15 - 16% loss of muscle tissue in my left ventricle: but fortunately not enough to affect my ejection fractions. But as to the issue of quinidine, my doctor - who by my dumb luck is currently the President Elect of the American College of Cardiology - told me that, with a normal Q - T interval, he didn't see that taking the drug would be an issue.

Finally - and perhaps most importantly - there is the issue of just what constitutes a recommended dosage, when the website notes concern "when recommended dosages are exceeded." So what are typical doses of quinidine sulfate for cardiac related issues? Significantly higher than Neudextra's 20 mg./day:

Hypertension: Recommended Dose: 100-200 mg daily given as a single dose in the morning or in divided doses (morning and evening). If needed, other antihypertensive agents may be added.

Long-term antihypertensive treatment with metoprolol in daily doses of 100-200 mg has been shown to reduce total mortality, including sudden cardiovascular death, stroke and coronary events in hypertensive patients.

Angina Pectoris: Recommended Dose: 100-200 mg daily given in divided doses (morning and evening). If needed, other antianginal agents may be added.

Cardiac Arrhythmias: Recommended Dose: 100-200 mg daily given in divided doses (morning and evening). If needed, other antiarrhythmic agents may be added.

Maintenance Treatment After Myocardial Infarction: Long-term oral treatment with metoprolol in doses of 200 mg daily given in divided doses (morning and evening) has been shown to reduce the risk of death (including sudden death) and to reduce the risk of reinfarction (also in patients with diabetes mellitus).

Functional Heart Disorders with Palpitations: Recommended Dose: 100 mg once daily given as a single dose in the morning. If needed, the dose can be increased to 200 mg. [Emphasis added.]

http://www.mimsonline.com/Philippine...nidine,sulfate

Indeed, the only drug interaction I happened to come across in the Drugs.com site with hard data concerned the co-administration of quinidine and methadone, where the mean amount of quinidine administered was 400 mg./day, or 20 times that of Nuedexta. http://www.drugs.com/drug-interactio...-0-1981-0.html

Accordingly, assuming there is a fresh EKG in hand, it is difficult for me to understand the risks posed by Nuedexta. That said, I remain open as always to education.

Mike

QT events can happen to normal people, people who PASS the EKG screening.

QT events happen when drugs interact at the level of the liver, and affect the metabolism of other drugs. Quinidine has historically been tested along with coumadin (warfarin) when new drugs are applied to the FDA...their inserts will list whether they interact or not with quinidine. It is a test standard of sorts.

If the quinidine in this new drug combo is strong enough to inhibit the metabolism of DM (which is a common OTC product), it can also affect other drugs a person takes.

Propulsid, Seldane and Hismanal were taken off the market because of drug interactions with erythromycin, oral antifungal drugs. Just taking Seldane for a short time with erythromycin resulted in DEATH. Propulsid, which is a motility agent, ran into trouble because people on blood pressure drugs in the diuretic family, were losing magnesium thru the urine, and low magnesium was enough to trigger a long QT event even when no genetic tendency was present. So after warning letters to doctors were ignored by them, the FDA was forced to remove this drug.

You can learn more about QT here:
http://www.azcert.org/

Much of the data on liver enzyme interactions is very complex and difficult to understand. And genetically people vary with this factor as well. If a person with a genetic issue in this area uses this drug combo, there may be effects that differ from other patients. Only DNA testing reveals this. (not the EKG).

So all the details aside...if the quinidine in this product is present enough to alter the metabolism of DM, it is enough to alter the metabolism of other drugs too.

Azcert link to quinidine:
http://www.azcert.org/medical-pros/d...-drug-list.cfm

Keep in mind...quinidine is an OLD drug not used anymore. Many doctors may be unfamiliar with it. And when things become focused on liver enzyme metabolism, many doctors'
eyes glaze over!

http://www.medscape.com/viewarticle/508543_2

Rxlist.com has a pretty comprehensive explanation of this drug in the pharmacology and precautions sections.
http://www.rxlist.com/nuedexta-drug.htm#

As I said before, treat with respect and care.
The example above is a TCA which is sometimes used in chronic pain patients. Raising blood levels 8 fold is significant. Also notice the statement that other drugs have NOT been studied in detail.

It is difficult to find up to date tables on these enzyme actions in the liver. Some tables do not list all the players accurately.
But interested readers here can look around and find one. It would be good to keep as a reference.

So the bottom line is ... potential for QT should be screened.
2) attention to hydration and electrolytes for all patients
3) Other drugs may be affected in a serious way...either becoming too strong or ineffective.

mrs D -

Thanks for all your hard work. I was aware of but overlooked (because they just slipped my mind, or what's left of it) the issues with serotonin syndrome, possibly because I can't tolerate SSRIs and the dose I take of Desipramine (10 mg./day) is so low that my psychopharmacologist considered any potentiation worth the risk. Still, my bad for not flagging the issue. :o

And the point that you make about younger docs in a hurry is a good one. Utterly inapplicable to my case, but that's beside the point.

I guess that at only 20 mg./day, it's got to be a professional judgment call. That said, are you aware of any information actually demonstrating that 20 mg./day of quinidine can trigger significant cardiac issues of any sort in a person with a clean EKG, genetic predisposition or not?

And then again, one guy's "making drugs too strong" is another's potentiation. Especially if it means avoiding some of the side effects that would otherwise be associated with increases doses of the other drug, e.g., DM potentiates opioids without increasing the risk of greater GI issues at higher doses.

Mike

I think the bottom line is even that the experts don't know everything. The Univ. of Arizona's work in this area is ongoing, meaning they add to it all the time. I remember many years ago how simple their website was. Not anymore!

Quinidine was popular 30 yrs ago... long before the new waves of sophisticated drugs arrived. Once the liver enzyme research heated up, and the new drugs became available, the QT and interaction data started to be compiled.

In fact the story behind how Seldane was discovered to be a deadly risk is pretty interesting. Seldane had been on the market for over 10 yrs and was losing its patent. Rugby generic already had it available and it was being dispensed. A professor at Georgetown Medical school discovered this cardiac sudden death thing by accident (meaning he wasn't looking for it). He started investigating this, and a brief period during which doctors were notified about this serious interaction and cardiac QT potential. They ignored the warning letters, and I remember a news show like 20/20 or Dateline going to pharmacies in NY with RXs for both Seldane and Erythromycin and none of the pharmacists caught it either, or called the doctors to change the combo. Since the parent company already had the active metabolite of Seldane ready to market (Allegra), it dropped its drug application for Seldane, which then made generics illegal in US. (generic Seldane is still available in other countries today however). And Allegra does not have this interaction potential either.

Some people genetically just cannot handle drug metabolism well. And it is difficult to predict still today. Not everyone who took Seldane with Erythromycin died...but many did, and it was attributed to "some other reason".

What I think the harmful potential of this drug combo is involves several potential areas for harm.
1)Used by people with genetic long QT situations, it is a risk. Something to watch and monitor and measure at the doctor's office. The FDA is putting the responsibility on the doctor.

2) people without genetic QT issues, can still have problems. The actual QT may occur when this drug combo is mixed with other medication. The Univ of Arizona has lists of high risk to low risk medications that when combined may affect heart rhythm. Anna Nicole Smith's son Daniel died from a combo of Lexapro and methadone...no overdoses, just a combo affecting his heart.

3) People without QT issues, can still have one if they become low in potassium and magnesium. Both these electrolytes affect conductivity in the heart. So throwing up alot, or having alot of diarrhea or not eating enough foods with adequate magnesium in them (very common in US)... can combine with this drug combo, to cause issues. Also many drugs may deplete potassium and magnesium. For example, diabetics excrete magnesium from the urine daily. Steroids deplete both electrolytes as well as diuretics.

4) this drug combo will interact with other drugs based on quinidine's effects on drug metabolism. That you have to look up on the charts, where quinidine is listed as a substrate inhibitor.

5) foods like grapefruit cannot be taken with this drug... because of its liver metabolism. Grapefruit paralyzes the GI lining which contains some of the Cytochrome P450 enzymes, so that a dose of drug appears higher in the blood than when grapefruit is not consumed.

So you see it is hard to predict what will happen. But for those who take many drugs, the risk increases. This is why having the charts is important. Some DNA testing sites have downloads for these enzyme systems, since they sell the tests. They also breakdown % based on ethnic race distribution if that is a factor. Some drugs are metabolized differently in Asians vs Africans vs Caucasians.

mrsD -

Great stuff! And I'll admit, I read the grapefruit ban in the PI sheet (as I do for every medication I'm on) despite the efforts of some drug makers to keep their FDA approved Prescribing Information unavailable to the public, but my doctor DID NOT mentioned it to me, although I've had to be off g.f. juice for a while now.

But I was particularly struck by your comments regarding the effects of sudden drops in electrolytes, whether from the flu or exercise on a hot day. My internist mentioned to me some time ago that's when people often O.D. from interactions at prescribed levels of drugs. (I know how wiped out my 14 year old son was after a hot hike - with water - until my wife had the good sense to give him a sports drink.)

I've been on a gram of magnesium a day for years, but only took Rx potassium when I was on Lasix. Sounds like this would be a great issue to publicize for the poly-medicated community, writ large.

Mike