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Drug Interactions between adenosine and Nuedexta

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

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Interactions between your drugs

Major

quiNIDine adenosine

Applies to: Nuedexta (dextromethorphan / quinidine) and adenosine

MONITOR CLOSELY: Adenosine has induced torsade de pointes arrhythmia in patients with preexisting long QT syndrome. Theoretically, coadministration of adenosine with agents that can prolong the QT interval may increase that risk as well. The mechanism has not been established, but may involve the depressant effect of adenosine on the sinoatrial and atrioventricular nodes. Rare cases of severe bradycardia have been reported during treatment with adenosine, which could favor the occurrence of torsade de pointes, especially in patients with prolonged QT intervals. Interestingly, no case of torsade de pointes has been reported when adenosine is given by continuous infusion.

MANAGEMENT: Adenosine should be used with caution in patients receiving drugs that are known to prolong the QT interval. Adenosine should be discontinued immediately if severe bradycardia occurs.

References (8)
  1. Wesley RC Jr, Turnquest P (1992) "Torsades de pointe after intravenous adenosine in the presence of prolonged QT syndrome." Am Heart J, 123, p. 794-6
  2. Tachakra SS, Robinson S (1992) "Adenosine and cardiac arrhythmias." BMJ, 305, p. 422
  3. Celiker A, Tokel K, Cil E, Ozkutlu S, Ozme S (1994) "Adenosine induced torsades de pointes in a child with congenital long QT syndrome." Pacing Clin Electrophysiol, 17, p. 1814-7
  4. Michalets EL, Williams CR (2000) "Drug interactions with cisapride: clinical implications." Clin Pharmacokinet, 39, p. 49-75
  5. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  6. Harrington GR, Froelich EG (1993) "Adenosine-induced torsades de pointes." Chest, 103, p. 1299-1301
  7. Mallet ML (2004) "Proarrhythmic effects of adenosine: a review of the literature." Emerg Med J, 21, p. 408-10
  8. Drescher MJ, Mendelssohn R (2002) "Transient torsades de pointes after adenosine." Isr J Trauma Intensive Care Emerg Med, 2, p. 15-7
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

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

adenosine food

Applies to: adenosine

ADJUST DOSING INTERVAL: Caffeine and other xanthine derivatives (e.g., theophylline) are nonspecific, competitive antagonists of adenosine receptors and may interfere with the hemodynamic effects of adenosine. There have been case reports of patients receiving theophylline who required higher than normal dosages of adenosine for the treatment of paroxysmal supraventricular tachycardia. In studies of healthy volunteers, caffeine and theophylline have been shown to reduce the cardiovascular response to adenosine infusions (i.e., heart rate increases, vasodilation, blood pressure changes), and theophylline has also been shown to attenuate adenosine-induced respiratory effects and chest pain/discomfort.

MANAGEMENT: Clinicians should be aware that adenosine may be less effective in the presence of xanthine derivatives including caffeine. Patients should avoid consumption of caffeine-containing products for at least 12 hours, preferably 24 hours, prior to administration of adenosine for myocardial perfusion imaging.

References (6)
  1. Conti CR (1991) "Adenosine: clinical pharmacology and applications." Clin Cardiol, 14, p. 91-3
  2. Smits P, Schouten J, Thien T (1987) "Respiratory stimulant effects of adenosine in man after caffeine and enprofylline." Br J Clin Pharmacol, 24, p. 816-9
  3. Minton NA, Henry JA (1991) "Pharmacodynamic interactions between infused adenosine and oral theophylline." Hum Exp Toxicol, 10, p. 411-8
  4. (2001) "Product Information. Adenocard (adenosine)." Fujisawa
  5. "Multum Information Services, Inc. Expert Review Panel"
  6. (2001) "Product Information. Adenoscan (adenosine)." Fujisawa
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

adenosine food

Applies to: adenosine

ADJUST DOSING INTERVAL: Methylxanthines (e.g., caffeine, theophylline) are nonspecific, competitive antagonists of adenosine receptors. As such, they may interfere with the pharmacologic effects of adenosine and other adenosine receptor agonists such as dipyridamole and regadenoson. There have been case reports of patients receiving theophylline who required higher than normal dosages of adenosine for the treatment of paroxysmal supraventricular tachycardia. In studies of healthy volunteers, caffeine and theophylline have been shown to reduce the cardiovascular response to adenosine infusions (i.e., heart rate increases, vasodilation, blood pressure changes), and theophylline has also been shown to attenuate adenosine-induced respiratory effects and chest pain/discomfort. Similarly, caffeine has been found to reduce the hemodynamic response to dipyridamole, and both caffeine and theophylline have been reported to cause false-negative results in myocardial scintigraphy tests using dipyridamole. In a placebo-controlled study that assessed the effects of oral caffeine on regadenoson-induced increase in coronary flow reserve (CFR), healthy subjects who took caffeine 200 mg orally two hours prior to regadenoson administration exhibited a median CFR that was 92% that of subjects who took placebo. The study was done using positron emission tomography with radiolabeled water.

MANAGEMENT: Clinicians should be aware that adenosine and other adenosine receptor agonists may be less effective in the presence of methylxanthines. Methylxanthines including caffeine should be withheld for 12 to 24 hours (or five half-lives) prior to administration of adenosine receptor agonists for myocardial perfusion imaging. However, parenteral aminophylline should be readily available for treating severe or persistent adverse reactions to adenosine receptor agonists such as bronchospasm or chest pain.

References (9)
  1. Conti CR (1991) "Adenosine: clinical pharmacology and applications." Clin Cardiol, 14, p. 91-3
  2. Smits P, Aengevaeren WR, Corstens FH, Thien T (1989) "Caffeine reduces dipyridamole-induced myocardial ischemia." J Nucl Med, 30, p. 1723-6
  3. Smits P, Schouten J, Thien T (1987) "Respiratory stimulant effects of adenosine in man after caffeine and enprofylline." Br J Clin Pharmacol, 24, p. 816-9
  4. Minton NA, Henry JA (1991) "Pharmacodynamic interactions between infused adenosine and oral theophylline." Hum Exp Toxicol, 10, p. 411-8
  5. (2002) "Product Information. Persantine (dipyridamole)." Boehringer-Ingelheim
  6. (2001) "Product Information. Adenocard (adenosine)." Fujisawa
  7. Ranhosky A, Kempthorne-Rawson J, the Intravenous Dipyridamole Thallium Imaging Study Group (1990) "The safety of intravenous dipyridamole thallium myocardial perfusion imaging." Circulation, 81, p. 1205-9
  8. (2001) "Product Information. Adenoscan (adenosine)." Fujisawa
  9. (2008) "Product Information. Lexiscan (regadenoson)." Astellas Pharma US, Inc
Minor

adenosine food

Applies to: adenosine

Nicotine may enhance adenosine-associated tachycardia and chest pain. The mechanism is not known. No special precautions appear to be necessary.

References (2)
  1. Smits P, Eijsbouts A, Thien T (1989) "Nicotine enhances the circulatory effects of adenosine in human beings." Clin Pharmacol Ther, 46, p. 272-8
  2. Sylven C, Beermann B, Kaijser L, Jonzon B (1990) "Nicotine enhances angina pectoris-like chest pain and atriovenricular blockade provoked by intravenous bolus of adenosine in healthy volunteers." J Cardiovasc Pharmacol, 16, p. 962-5

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:

  • adenosine
  • 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.


Report options

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.