Interactions between Dextromethorphan / quinidine and Tecovirimat
2 drug interactions and 15 additional warnings found for the following 2 drugs:
- dextromethorphan/quinidine
- tecovirimat
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 tecovirimat
Applies to: dextromethorphan / quinidine and tecovirimat
Monitor
Coadministration with tecovirimat may decrease the plasma concentrations of drugs that are primarily metabolized by CYP450 3A4. Tecovirimat is a weak inducer of CYP450 3A4. In a drug interaction study involving 24 healthy subjects, a single 2 mg dose of midazolam was coadministered with tecovirimat (600 mg twice daily), and the midazolam peak plasma concentration (Cmax) and systemic exposure (AUC) decreased by 39% and 32%, respectively.
Management
The potential for diminished pharmacologic effects of CYP450 3A4 substrates should be considered during coadministration with tecovirimat.
References (2)
- (2024) "Product Information. Tpoxx (tecovirimat)." SIGA Technologies, Inc., FDA 8
- (2025) "Product Information. Tpoxx (tecovirimat)." Innomar Strategies Inc, 289138
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:
tecovirimat Food/Lifestyle
Applies to: tecovirimat
Adjust dosing interval
Food may increase the extent of tecovirimat absorption following oral administration. When the recommended oral dose of tecovirimat (600 mg every 12 hours) was administered with a meal (approximately 600 calories and 25 g of fat) in healthy adults weighing less than 120 kg, tecovirimat absorption increased by 39% relative to fasting.
Management
Oral tecovirimat should be taken within 30 minutes after a full meal containing moderate or high fat (approximately 600 calories and 25 g of fat) with 6 to 8 ounces of water.
References (2)
- (2024) "Product Information. Tpoxx (tecovirimat)." SIGA Technologies, Inc., FDA 8
- (2025) "Product Information. Tpoxx (tecovirimat)." Innomar Strategies Inc, 289138
Disease interactions
12 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.
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.
Smallpox
Major:
tecovirimat
Tecovirimat has a major potential interaction with Smallpox.
Tecovirimat injection is contraindicated in patients with severe renal dysfunction (CrCl below 30 mL/min).
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.
Report options
More resources
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.
tecovirimat
A total of 313 drugs are known to interact with tecovirimat.
- Tecovirimat is in the drug class miscellaneous antivirals.
- Tecovirimat is used to treat the following conditions:
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
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.