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Drug Interactions between flecainide and Nuedexta

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

quiNIDine dextromethorphan

Applies to: Nuedexta (dextromethorphan / quinidine) and Nuedexta (dextromethorphan / quinidine)

GENERALLY AVOID: Coadministration with potent CYP450 2D6 inhibitors (e.g., quinidine, terbinafine) may significantly increase the plasma concentrations of dextromethorphan in patients who are extensive metabolizers of this isoenzyme (approximately 93% of Caucasians and more than 98% of Asians and individuals of African descent). The proposed mechanism is inhibition of the CYP450 2D6-mediated O-demethylation of dextromethorphan. Studies in humans have shown an increase in systemic exposure of dextromethorphan of up to 43-fold when given concurrently with quinidine. Increased plasma concentrations increase the risk of dextromethorphan-related adverse effects (e.g., agitation, confusion, tremor, insomnia, diarrhea, and respiratory depression) and serotonin syndrome. However, this interaction has also been used clinically, with dextromethorphan in combination with quinidine indicated by some authorities for the treatment of pseudobulbar affect. Data evaluating the impact of this interaction in patients who are poor metabolizers of CYP450 2D6 are limited; most studies include extensive metabolizers of this isoenzyme. It is expected that poor metabolizers would have elevated dextromethorphan levels without concurrent quinidine

MANAGEMENT: The combination of dextromethorphan with potent CYP450 2D6 inhibitors should be generally avoided. Some manufacturers consider the concomitant use of dextromethorphan and selective serotonin reuptake inhibitors contraindicated. If use is considered necessary, the patient should be monitored for signs of dextromethorphan adverse effects (e.g., agitation, confusion, tremor, insomnia, diarrhea, and respiratory depression) and serotonin syndrome, and advised to notify their health care professional if these adverse effects develop or worsen. Dose reduction of dextromethorphan may also be required.

References (6)
  1. Zhang Y, Britto MR, Valderhaug KL, Wedlund PJ, Smith RA (1992) "Dextromethorphan: enhancing its systemic availability by way of low-dose quinidine-mediated inhibition of cytochrome P4502D6." Clin Pharmacol Ther, 51, p. 647-55
  2. Schadel M, Wu DA, Otton SV, Kalow W, Sellers EM (1995) "Pharmacokinetics of dextromethorphan and metabolites in humans: influence of the CYP2d6 phenotype and quinidine inhibition." J Clin Psychopharmacol, 15, p. 263-9
  3. Capon DA, Bochner F, Kerry N, Mikus G, Danz C, Somogyi AA (1996) "The influence of CYP2d6 polymorphism and quinidine on the disposition and antitussive effect of dextromethorphan in humans." Clin Pharmacol Ther, 60, p. 295-307
  4. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  5. Cerner Multum, Inc. "Australian Product Information."
  6. (2010) "Product Information. Nuedexta (dextromethorphan-quinidine)." Avanir Pharmaceuticals, Inc
Moderate

quiNIDine flecainide

Applies to: Nuedexta (dextromethorphan / quinidine) and flecainide

MONITOR: Quinidine may decrease the CYP450 2D6 hepatic metabolism of flecainide in some patients. Serum flecainide levels and the risk of toxicity may be increased. Extensive debrisoquine metabolizers may be at greater risk of toxicity.

MANAGEMENT: Patients should be monitored for flecainide side effects and ECG changes after quinidine is added to the regimen. A reduction in flecainide dosage may be necessary. Patients should be advised to notify their physician if they experience dizziness, confusion, nausea, vomiting, syncope, blurry vision, changes in pulse rate, or increased irregular heartbeats.

References (2)
  1. Munafo A, Buclin T, Tuto D, Biollaz J (1992) "The effect of a low dose of quinidine on the disposition of flecainide in healthy volunteers." Eur J Clin Pharmacol, 43, p. 441-3
  2. Munafo A, Buclin T, Steinhausen F, Biollaz J (1990) "Disposition of flecainide in subjects taking quinidine." Clin Pharmacol Ther, 47, p. 156

Drug and food interactions

Moderate

quiNIDine food

Applies to: Nuedexta (dextromethorphan / quinidine)

GENERALLY AVOID: In a small, randomized, crossover study, the administration of quinidine with grapefruit juice (compared to water) to healthy volunteers significantly prolonged the time to reach peak plasma quinidine concentrations and decreased the plasma concentrations of its major metabolite, 3-hydroxyquinidine. These changes were associated pharmacodynamically with both a delay and a reduction in the maximal effect on QTc interval. The proposed mechanism is delay of gastric emptying as well as inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruits.

MANAGEMENT: Given the drug's narrow therapeutic index, patients receiving quinidine therapy should avoid the consumption of grapefruits and grapefruit juice to prevent any undue fluctuations in plasma drug levels.

References (4)
  1. Ace LN, Jaffe JM, Kunka RL (1983) "Effect of food and an antacid on quinidine bioavailability." Biopharm Drug Dispos, 4, p. 183-90
  2. Min DI, Ku YM, Geraets DR, Lee HC (1996) "Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers." J Clin Pharmacol, 36, p. 469-76
  3. Ha HR, Chen J, Leuenberger PM, Freiburghaus AU, Follah F (1995) "In vitro inhibition of midazolam and quinidine metabolism by flavonoids." Eur J Clin Pharmacol, 48, p. 367-71
  4. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
Moderate

dextromethorphan food

Applies to: Nuedexta (dextromethorphan / quinidine)

GENERALLY AVOID: Alcohol may potentiate some of the pharmacologic effects of CNS-active agents. Use in combination may result in additive central nervous system depression and/or impairment of judgment, thinking, and psychomotor skills.

MANAGEMENT: Patients receiving CNS-active agents should be warned of this interaction and advised to avoid or limit consumption of alcohol. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to notify their physician if they experience excessive or prolonged CNS effects that interfere with their normal activities.

References (4)
  1. Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P (1990) "Goodman and Gilman's the Pharmacological Basis of Therapeutics." New York, NY: Pergamon Press Inc.
  3. (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
  4. (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka American Pharmaceuticals Inc
Moderate

flecainide food

Applies to: flecainide

MONITOR: Smoking cessation may lead to elevated plasma concentrations and enhanced pharmacologic effects of drugs that are substrates of CYP450 1A2 (and possibly CYP450 1A1) and/or certain drugs with a narrow therapeutic index (e.g., flecainide, pentazocine). One proposed mechanism is related to the loss of CYP450 1A2 and 1A1 induction by polycyclic aromatic hydrocarbons in tobacco smoke; when smoking cessation agents are initiated and smoking stops, the metabolism of certain drugs may decrease leading to increased plasma concentrations. The mechanism by which smoking cessation affects narrow therapeutic index drugs that are not known substrates of CYP450 1A2 or 1A1 is unknown. The clinical significance of this interaction is unknown as clinical data are lacking.

MANAGEMENT: Until more information is available, caution is advisable if smoking cessation agents are used concomitantly with drugs that are substrates of CYP450 1A2 or 1A1 and/or those with a narrow therapeutic range. Patients receiving smoking cessation agents may require periodic dose adjustments and closer clinical and laboratory monitoring of medications that are substrates of CYP450 1A2 or 1A1.

References (4)
  1. (2024) "Product Information. Cytisine (cytisinicline)." Consilient Health Ltd
  2. jeong sh, Newcombe D, sheridan j, Tingle M (2015) "Pharmacokinetics of cytisine, an a4 b2 nicotinic receptor partial agonist, in healthy smokers following a single dose." Drug Test Anal, 7, p. 475-82
  3. Vaughan DP, Beckett AH, Robbie DS (1976) "The influence of smoking on the intersubject variation in pentazocine elimination." Br J Clin Pharmacol, 3, p. 279-83
  4. Zevin S, Benowitz NL (1999) "Drug interactions with tobacco smoking: an update" Clin Pharmacokinet, 36, p. 425-38

Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Antiarrhythmics

Therapeutic duplication

The recommended maximum number of medicines in the 'antiarrhythmics' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'antiarrhythmics' category:

  • flecainide
  • Nuedexta (dextromethorphan/quinidine)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

Duplication

Group i antiarrhythmics

Therapeutic duplication

The recommended maximum number of medicines in the 'group I antiarrhythmics' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'group I antiarrhythmics' category:

  • flecainide
  • Nuedexta (dextromethorphan/quinidine)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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