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.
Quote:
MAOIs
Do not use NUEDEXTA with monoamine oxidase inhibitors (MAOIs) or in patients who have taken MAOIs within the preceding 14 days [see CONTRAINDICATIONS].
Drugs that Prolong QT and are Metabolized by CYP2D6
Do not use with drugs that both prolong QT interval and are metabolized by CYP2D6 (e.g., thioridazine or pimozide) [see CONTRAINDICATIONS].
Drugs that Prolong QT and Concomitant CYP3A4 Inhibitors
Recommend ECG in patients taking drugs with NUEDEXTA that prolong the QT interval and in patients taking concomitant moderate or strong CYP3A4 inhibitors [see WARNINGS AND PRECAUTIONS].
SSRIs and Tricyclic Antidepressants
Use of NUEDEXTA with SSRIs or tricyclic antidepressants increases the risk of 'serotonin syndrome' [see WARNINGS AND PRECAUTIONS]
CYP2D6 Substrate
The co-administration of NUEDEXTA with drugs that undergo extensive CYP2D6 metabolism may result in altered drug effects, due to accumulation of parent drug and/or failure of metabolite formation [see WARNINGS AND PRECAUTIONS]. Therapy with medications that are primarily metabolized by CYP2D6 and that have a relatively narrow therapeutic index should be initiated at a low dose if a patient is receiving NUEDEXTA concurrently. If NUEDEXTA is added to the treatment regimen of a patient already receiving a drug primarily metabolized by CYP2D6, the need for a dose modification of the original medication should be considered. The extent to which CYP2D6 interactions may pose clinical problems will depend on the pharmacokinetics of the substrate involved.
In cases of prodrugs whose actions are mediated by the CYP2D6-produced metabolites (for example, codeine and hydrocodone, whose analgesic and antitussive effects appear to be mediated by morphine and hydromorphone, respectively), it may not be possible to achieve the desired clinical benefits in the presence of NUEDEXTA due to quinidine-mediated inhibition of CYP2D6. Consider use of alternative treatment with NUEDEXTA when clinically indicated.
Drug interactions with desipramine and paroxetine have been studied in controlled clinical trials with a higher dose combination of dextromethorphan/quinidine (dextromethorphan 30 mg/quinidine 30 mg) than NUEDEXTA; study results are described below. No other drug interactions with CYP2D6 substrates have been systematically investigated, although concomitant use of such drugs was allowed in clinical trials with NUEDEXTA and in clinical trials with higher dose formulations of dextromethorphan/quinidine.
Desipramine (CYP2D6 substrate): The tricyclic antidepressant desipramine is metabolized primarily by CYP2D6. A drug interaction study was conducted between a higher combination dose of dextromethorphan (dextromethorphan 30 mg/quinidine 30 mg) and desipramine 25 mg. The combination dose of dextromethorphan/quinidine increased steady state desipramine levels approximately 8-fold. If NUEDEXTA and desipramine are prescribed concomitantly, the initial dose of desipramine should be markedly reduced. The dose of desipramine can then be adjusted based on clinical response; however, a dose above 40 mg/day is not recommended.
Paroxetine (CYP2D6 inhibitor and substrate): When the combination dose of dextromethorphan 30 mg/quinidine 30 mg was added to paroxetine at steady state, paroxetine exposure (AUC0-24) increased by 1.7 fold and Cmax increased by 1.5 fold. Consideration should be given to initiating treatment with a lower dose of paroxetine if given with NUEDEXTA. The dose of paroxetine can then be adjusted based on clinical response; however, dosage above 35 mg/day is not recommended.
Digoxin
Quinidine is an inhibitor of P-glycoprotein. Concomitant administration of quinidine with digoxin, a P-glycoprotein substrate, results in serum digoxin levels that may be as much as doubled. Plasma digoxin concentrations should be closely monitored in patients taking NUEDEXTA concomitantly, and the digoxin dose reduced, as necessary.
Alcohol
As with any other CNS drug, caution should be used when NUEDEXTA is taken in combination with other centrally acting drugs and alcohol.
Drug Abuse And Dependence
NUEDEXTA is a low-affinity uncompetitive NMDA antagonist and sigma-1 receptor agonist that has not been systematically studied in animals or humans for its potential for abuse, tolerance, or physical dependence. However, NUEDEXTA is a combination product containing dextromethorphan and quinidine, and cases of dextromethorphan abuse have been reported, predominantly in adolescents.
While clinical trials did not reveal drug-seeking behavior, these observations were not systematic and it is not possible to predict on the basis of this experience the extent to which NUEDEXTA will be misused, diverted, and/or abused once marketed. Therefore, patients with a history of drug abuse should be observed closely for signs of NUEDEXTA misuse or abuse (e.g. development of tolerance, increases in dose, drug-seeking behavior).
Last reviewed on RxList: 12/10/2010
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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.
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All truths are easy to understand once they are discovered; the point is to discover them.-- Galileo Galilei
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Weezie looking at petunias 8.25.2017
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