Interactions between Dextromethorphan / quinidine and Vorasidenib
2 drug interactions and 17 additional warnings found for the following 2 drugs:
- dextromethorphan/quinidine
- vorasidenib
Drug interactions
Major drug interactions
Major:
quiNIDine dextromethorphan
Applies to: dextromethorphan / quinidine and dextromethorphan / quinidine
Generally avoid
Coadministration with potent CYP450 2D6 inhibitors may significantly increase the plasma concentrations of dextromethorphan, which is primarily metabolized by this isoenzyme. Approximately 93% of Caucasians and more than 98% of Asians and individuals of African descent are extensive metabolizers of CYP450 2D6 and may be affected by this interaction. Studies in humans have shown an increase in systemic exposure (AUC) to dextromethorphan of up to 43-fold when given concurrently with quinidine. However, this interaction is also used clinically and is indicated by some authorities for the treatment of pseudobulbar affect (dextromethorphan/quinidine) and major depressive disorder (dextromethorphan/bupropion). Data evaluating the impact of this interaction in patients who are poor metabolizers of CYP450 2D6 are limited, as most studies include extensive metabolizers. It is expected that poor metabolizers would have elevated dextromethorphan levels even without concurrent CYP450 2D6 inhibitors.
Management
The combination of dextromethorphan with potent CYP450 2D6 inhibitors should be generally avoided. If the potent CYP450 2D6 inhibitor is also a selective serotonin reuptake inhibitor (e.g. fluoxetine, paroxetine), some manufacturers consider coadministration 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 reductions of dextromethorphan may also be necessary or required for certain formulations. Additional consultation with individual product labeling may be advisable for further guidance.
References (8)
- 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
- 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
- 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
- (2024) "Product Information. Bisolvon Dry (dextromethorphan)." Sanofi-Aventis Australia Pty Ltd
- (2014) "Product Information. CINFATOS (dextrometorfano)." LABORATORIOS CINFA, S.A.
- (2025) "Product Information. Auvelity (bupropion-dextromethorphan)." Axsome Therapeutics, Inc.
- (2019) "Product Information. Nuedexta (dextromethorphan-quinidine)." Avanir Pharmaceuticals, Inc, DM 29
- (2025) "Product Information. Benylin Dry Coughs (dextromethorphan)." McNeil Products Ltd
Moderate drug interactions
Moderate:
quiNIDine vorasidenib
Applies to: dextromethorphan / quinidine and vorasidenib
Generally avoid
Concomitant use with multiple doses of vorasidenib may decrease the plasma concentrations of drugs that are substrates of CYP450 3A4, CYP450 2C19, or CYP450 2B6. Vorasidenib is predicted to induce these isoenzymes, resulting in increased metabolism and reduced exposure of affected drugs. Based on in vitro studies and physiologically based pharmacokinetic modeling, vorasidenib is predicted to decrease exposure of sensitive CYP450 3A4 substrates by approximately 80%, sensitive CYP450 2C19 substrates by 30% to 35%, and sensitive CYP450 2B6 substrates by approximately 20%. The interaction may be more clinically significant for sensitive CYP450 3A4 substrates and for CYP450 3A4, CYP450 2C19, or CYP450 2B6 substrates with a narrow therapeutic index, where reduced exposure may lead to diminished therapeutic effect.
Management
Concomitant use of vorasidenib with sensitive CYP450 3A4 substrates or substrates of CYP450 3A4, CYP450 2C19, or CYP450 2B6 with a narrow therapeutic index should generally be avoided. Consider alternative therapies when appropriate. If concomitant use cannot be avoided, monitor patients for reduced therapeutic response and adjust therapy as clinically indicated. Consult the relevant product labeling for additional recommendations regarding concomitant use, including patient selection, monitoring, and dose modification, as applicable.
References (5)
- Multicenter Study Group (2024) Center for drug evaluation and research. Application number: 218784Orig1s000. Integrated review. https://www.accessdata.fda.gov/drugsatfda_docs/nda/2024/218784Orig1s000MultidisciplineR.pdf
- (2026) "Product Information. Voranigo (vorasidenib)." Servier Laboratories Ltd
- (2026) "Product Information. Voranigo (vorasidenib)." Servier Laboratories (Australia) Pty Ltd, Version: 2
- (2025) "Product Information. Voranigo (vorasidenib)." Servier Pharmaceuticals LLC
- (2026) "Product Information. Voranigo (vorasidenib)." Servier Canada Inc
Food/lifestyle interactions
Moderate food/lifestyle interactions
Moderate:
quiNIDine Food/Lifestyle
Applies to: 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)
- Ace LN, Jaffe JM, Kunka RL (1983) "Effect of food and an antacid on quinidine bioavailability." Biopharm Drug Dispos, 4, p. 183-90
- 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
- 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
- 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/Lifestyle
Applies to: 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)
- Warrington SJ, Ankier SI, Turner P (1986) "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology, 15, p. 31-7
- 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.
- (2012) "Product Information. Fycompa (perampanel)." Eisai Inc
- (2015) "Product Information. Rexulti (brexpiprazole)." Otsuka America Pharmaceutical, Inc.
Moderate:
vorasidenib Food/Lifestyle
Applies to: vorasidenib
Generally avoid
Smoking tobacco during treatment may decrease vorasidenib plasma concentrations and reduce its anti-tumor activity. The mechanism is tobacco smoking-mediated induction of CYP450 1A2, the isoenzyme primarily responsible for the metabolic clearance of vorasidenib. Clinical and pharmacokinetic data are currently lacking. In addition, because vorasidenib can cause hepatotoxicity, concomitant use with alcohol may further increase the risk of liver injury. Clinical data evaluating this interaction are also lacking.
Monitor
In pharmacokinetic studies, food increased vorasidenib exposure. High-fat meals increased vorasidenib systemic exposure (AUC) and peak plasma concentration (Cmax) by 1.4-fold and 3.1-fold, respectively, while low-fat meals increased AUC and Cmax by 1.4-fold and 2.3-fold, respectively. However, the manufacturer does not consider this effect as clinically significant.
Management
Patients should be advised to avoid smoking tobacco during treatment with vorasidenib. According to its product labeling, vorasidenib may be taken with or without food. In addition, patients should be advised to avoid excessive alcohol consumption during treatment. Liver function tests should be monitored according to the manufacturer's recommendations, and patients should promptly report signs and symptoms of liver injury.
References (4)
- (2026) "Product Information. Voranigo (vorasidenib)." Servier Laboratories Ltd
- (2026) "Product Information. Voranigo (vorasidenib)." Servier Laboratories (Australia) Pty Ltd, Version: 2
- (2025) "Product Information. Voranigo (vorasidenib)." Servier Pharmaceuticals LLC
- (2026) "Product Information. Voranigo (vorasidenib)." Servier Canada Inc
Disease interactions
14 potential interactions Applies to: 12 conditions, including Heart Failure, Hypokalemia, Hypotension, Myasthenia Gravis, and Urinary Retention.
Glaucoma/Intraocular Hypertension
Major:
dextromethorphan / quinidine
The quiNIDine in dextromethorphan / quinidine has a major potential interaction with Glaucoma/Intraocular Hypertension.
The use of quinidine is contraindicated in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as myasthenia gravis, glaucoma, and urinary retention or obstruction.
Heart Block
Major:
dextromethorphan / quinidine
The quiNIDine in dextromethorphan / quinidine has a major potential interaction with Heart Block.
The use of quinidine is contraindicated for use in patients without a functioning artificial pacemaker whose cardiac rhythm is dependent upon a junctional or idioventricular pacemaker, including patients with complete AV block. Therapy with quinidine should be administered with caution in patients with severe sinus-node dysfunction such as sick sinus syndrome, bradycardia-tachycardia syndrome, or second- or third-degree heart block.
Heart Failure
Major:
dextromethorphan / quinidine
The quiNIDine in dextromethorphan / quinidine has a major potential interaction with Heart Failure.
Antiarrhythmic agents can induce severe hypotension (particularly with IV administration) or induce or worsen congestive heart failure (CHF). Patients with primary cardiomyopathy or inadequately compensated CHF are at increased risk. Antiarrhythmic agents should be administered cautiously and dosage and/or frequency of administration modified in patients with hypotension or adequately compensated CHF. Alternative therapy should be considered unless these conditions are secondary to cardiac arrhythmia.
Hyperkalemia
Moderate:
dextromethorphan / quinidine
The quiNIDine in dextromethorphan / quinidine has a moderate potential interaction with Hyperkalemia.
Electrolyte imbalance can alter the therapeutic effectiveness of antiarrhythmic agents. Hypokalemia and hypomagnesemia can reduce the effectiveness of antiarrhythmic agents. In some cases, these disorders can exaggerate the degree of QTc prolongation and increase the potential for torsade de pointes. Hyperkalemia can potentiate the toxic effects of antiarrhythmic agents. Electrolyte imbalance should be corrected prior to initiating antiarrhythmic therapy. Clinical monitoring of cardiac function and electrolyte concentrations is recommended.
Hypokalemia
Moderate:
dextromethorphan / quinidine
The quiNIDine in dextromethorphan / quinidine has a moderate potential interaction with Hypokalemia.
Electrolyte imbalance can alter the therapeutic effectiveness of antiarrhythmic agents. Hypokalemia and hypomagnesemia can reduce the effectiveness of antiarrhythmic agents. In some cases, these disorders can exaggerate the degree of QTc prolongation and increase the potential for torsade de pointes. Hyperkalemia can potentiate the toxic effects of antiarrhythmic agents. Electrolyte imbalance should be corrected prior to initiating antiarrhythmic therapy. Clinical monitoring of cardiac function and electrolyte concentrations is recommended.
Hypotension
Major:
dextromethorphan / quinidine
The quiNIDine in dextromethorphan / quinidine has a major potential interaction with Hypotension.
Antiarrhythmic agents can induce severe hypotension (particularly with IV administration) or induce or worsen congestive heart failure (CHF). Patients with primary cardiomyopathy or inadequately compensated CHF are at increased risk. Antiarrhythmic agents should be administered cautiously and dosage and/or frequency of administration modified in patients with hypotension or adequately compensated CHF. Alternative therapy should be considered unless these conditions are secondary to cardiac arrhythmia.
Liver Disease
Moderate:
dextromethorphan / quinidine
The quiNIDine in dextromethorphan / quinidine has a moderate potential interaction with Liver Disease.
Quinidine is primarily metabolized by the liver to active and inactive forms. Hepatic dysfunction causes a slowed metabolism and elimination of the drug which can lead to quinidine toxicity if dosage is not appropriately reduced. Clinical monitoring of hepatic function is recommended.
Moderate:
vorasidenib
Vorasidenib has a moderate potential interaction with Liver Disease.
The pharmacokinetics and safety of vorasidenib have not been studied in patients with severe liver dysfunction (Child-Pugh C); these patients should be monitored for increased adverse reactions and the dosage should be modified for adverse reactions as recommended in the manufacturer product information. No dosage adjustment is recommended for patients with mild or moderate liver dysfunction (Child-Pugh A or B).
Magnesium Imbalance
Moderate:
dextromethorphan / quinidine
The quiNIDine in dextromethorphan / quinidine has a moderate potential interaction with Magnesium Imbalance.
Electrolyte imbalance can alter the therapeutic effectiveness of antiarrhythmic agents. Hypokalemia and hypomagnesemia can reduce the effectiveness of antiarrhythmic agents. In some cases, these disorders can exaggerate the degree of QTc prolongation and increase the potential for torsade de pointes. Hyperkalemia can potentiate the toxic effects of antiarrhythmic agents. Electrolyte imbalance should be corrected prior to initiating antiarrhythmic therapy. Clinical monitoring of cardiac function and electrolyte concentrations is recommended.
Myasthenia Gravis
Major:
dextromethorphan / quinidine
The quiNIDine in dextromethorphan / quinidine has a major potential interaction with Myasthenia Gravis.
The use of quinidine is contraindicated in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as myasthenia gravis, glaucoma, and urinary retention or obstruction.
Renal Dysfunction
Moderate:
dextromethorphan / quinidine
The quiNIDine in dextromethorphan / quinidine has a moderate potential interaction with Renal Dysfunction.
Renal dysfunction causes a slowed elimination of quinidine which can lead to quinidine toxicity if dosage is not appropriately reduced. Therapy with quinidine should be administered cautiously and dosages reduced in patients with compromised renal function. Quinidine is not appreciably removed by hemodialysis.
Moderate:
vorasidenib
Vorasidenib has a moderate potential interaction with Renal Dysfunction.
The pharmacokinetics and safety of vorasidenib have not been studied in patients with CrCl up to 40 mL/min or renal dysfunction requiring dialysis; these patients should be monitored for increased adverse reactions and the dosage should be modified for adverse reactions as recommended in the manufacturer product information. No dosage adjustment is recommended for patients with CrCl greater than 40 mL/min.
Smoking
Moderate:
vorasidenib
Vorasidenib has a moderate potential interaction with Smoking.
Tobacco smoking may decrease vorasidenib plasma levels, which may reduce its antitumor activity. Patients and caregivers should be advised to inform their health care provider if they currently smoke tobacco.
Urinary Retention
Major:
dextromethorphan / quinidine
The quiNIDine in dextromethorphan / quinidine has a major potential interaction with Urinary Retention.
The use of quinidine is contraindicated in patients with preexisting conditions that are likely to be exacerbated by anticholinergic activity, such as myasthenia gravis, glaucoma, and urinary retention or obstruction.
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dextromethorphan / quinidine
A total of 850 drugs are known to interact with dextromethorphan / quinidine.
- Dextromethorphan / quinidine is in the drug class miscellaneous central nervous system agents.
- Dextromethorphan / quinidine is used to treat Pseudobulbar Affect.
vorasidenib
A total of 450 drugs are known to interact with vorasidenib.
- Vorasidenib is in the drug class miscellaneous antineoplastics.
- Vorasidenib is used to treat Malignant Glioma.
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| 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. | |
| No interaction information available. |
Further information
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