Interactions between Aliskiren and Dextromethorphan / quinidine
2 drug interactions and 20 additional warnings found for the following 2 drugs:
- aliskiren
- dextromethorphan/quinidine
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 aliskiren
Applies to: dextromethorphan / quinidine and aliskiren
Monitor
Coadministration with potent inhibitors of P-glycoprotein may significantly increase the plasma concentrations and pharmacologic effects of aliskiren. The proposed mechanism is inhibition of the intestinal efflux of aliskiren via P-glycoprotein. According to the product labeling, administration of a 75 mg dose of aliskiren in combination with 200 mg and 600 mg cyclosporine, a highly potent P-glycoprotein inhibitor, resulted in an approximately 2.5-fold increase in aliskiren peak plasma concentration (Cmax) and a 5-fold increase in systemic exposure (AUC). Coadministration of 300 mg aliskiren with 240 mg verapamil, a moderate P-glycoprotein inhibitor, resulted in an approximately 2-fold increase in aliskiren Cmax and AUC.
Management
Pharmacologic response to aliskiren should be monitored more closely whenever a P-glycoprotein inhibitor is added to or withdrawn from therapy, and the aliskiren dosage adjusted as necessary. Patients should be advised to notify their physician if they experience excessive adverse effects of aliskiren such as dizziness, lightheadedness, diarrhea, abdominal pain, and gastroesophageal reflux. The product labeling states that no dosage adjustment is necessary during coadministration with verapamil. Nevertheless, patients should be monitored for potentially increased effects of aliskiren.
References (1)
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
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:
aliskiren Food/Lifestyle
Applies to: aliskiren
Generally avoid
Coadministration with orange, apple, or grapefruit juice may significantly decrease the oral bioavailability and renin-inhibiting effect of aliskiren. The exact mechanism of interaction is unknown, but may include inhibition of OATP2B1-mediated influx of aliskiren in the small intestine, formation of insoluble complexes between fruit juice constituents and aliskiren, and/or increased ionization of aliskiren due to reduced intestinal pH. In 12 healthy volunteers, 200 mL of either orange juice or apple juice administered three times daily for 5 days in combination with a single 150 mg oral dose of aliskiren on day 3 reduced the mean aliskiren peak plasma concentration (Cmax) and systemic exposure (AUC) by approximately 80% and 60%, respectively, compared to water. Plasma renin activity was 87% and 67% higher at 24 hours postdose when aliskiren was administered with orange juice and apple juice, respectively, compared to water. No significant differences were observed in the blood pressure or heart rate between treatments. However, this may be due to the delayed onset of aliskiren's blood pressure-lowering effect, which would not be apparent following a single dose. A similar pharmacokinetic interaction has been reported with grapefruit juice. In 11 healthy volunteers, 200 mL of normal strength grapefruit juice administered three times daily for 5 days in combination with a single 150 mg oral dose of aliskiren on day 3 reduced the mean aliskiren Cmax and AUC by 81% and 61%, respectively, but there was no change in plasma renin activity compared to water. A high degree of interpatient variability was observed with all three interactions.
Monitor
High-fat meals can substantially reduce the gastrointestinal absorption of aliskiren. According to the product labeling, administration of aliskiren with a high-fat meal decreased the mean peak plasma concentration (Cmax) and systemic exposure (AUC) by 85% and 71%, respectively. In clinical trials, however, aliskiren was administered without a fixed requirement in relation to meals.
Management
To ensure steady systemic drug levels and therapeutic effects, patients should establish a routine pattern for administration of aliskiren with regard to meals. Coadministration with orange, apple, or grapefruit juice should be avoided, especially if these juices are to be consumed on a regular basis or shortly before or after aliskiren dosing.
References (4)
- (2007) "Product Information. Tekturna (aliskiren)." Novartis Pharmaceuticals
- Vaidyanathan S, Jarugula V, Dieterich HA, Howard D, Dole WP (2008) "Clinical pharmacokinetics and pharmacodynamics of aliskiren." Clin Pharmacokinet, 47, p. 515-31
- Tapaninen T, Neuvonen PJ, Niemi M (2010) "Grapefruit juice greatly reduces the plasma concentrations of the OATP2B1 and CYP3A4 substrate aliskiren." Clin Pharmacol Ther, 88, p. 339-42
- Tapaninen T, Neuvonen PJ, Niemi M (2010) "Orange and apple juices greatly reduce the plasma concentrations of the OATP2B1 substrate aliskiren." Br J Clin Pharmacol, 71, p. 718-26
Disease interactions
17 potential interactions Applies to: 15 conditions, including Heart Failure, Hypokalemia, Hypotension, Myasthenia Gravis, and Diabetes Mellitus.
Dehydration
Moderate:
aliskiren
Aliskiren has a moderate potential interaction with Dehydration.
Symptomatic hypotension may occur after treatment initiation with aliskiren in patients with marked volume depletion, salt depletion, or with combined use of aliskiren and other agents acting on the renin-angiotensin-aldosterone system. It is recommended to correct the volume or salt depletion before administering aliskiren. Close monitoring is recommended.
Diabetes Mellitus
Major:
aliskiren
Aliskiren has a major potential interaction with Diabetes Mellitus.
The use of aliskiren is contraindicated in patients with diabetes who are receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARBs), as there is an increased risk of renal impairment, hyperkalemia, and hypotension.
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.
Moderate:
aliskiren
Aliskiren has a moderate potential interaction with Heart Failure.
Renal function should be monitored periodically in patients treated with aliskiren, as changes can occur including acute renal failure. Patients on aliskiren whose renal function may depend in part of the RAAS (renin-angiotensin-aldosterone system), such as patients with renal artery stenosis, severe heart failure, or postmyocardial infarction may be at higher risk for developing acute renal failure. Treatment should be discontinued in any patients who develop clinically significant decrease in renal function. Patients with renal impairment should be observed closely. The safety and effectiveness of aliskiren have not been established in patients with severe renal impairment (CrCl < 30 mL/min), as these patients were excluded from clinical trials.
History - Myocardial Infarction
Moderate:
aliskiren
Aliskiren has a moderate potential interaction with History - Myocardial Infarction.
Renal function should be monitored periodically in patients treated with aliskiren, as changes can occur including acute renal failure. Patients on aliskiren whose renal function may depend in part of the RAAS (renin-angiotensin-aldosterone system), such as patients with renal artery stenosis, severe heart failure, or postmyocardial infarction may be at higher risk for developing acute renal failure. Treatment should be discontinued in any patients who develop clinically significant decrease in renal function. Patients with renal impairment should be observed closely. The safety and effectiveness of aliskiren have not been established in patients with severe renal impairment (CrCl < 30 mL/min), as these patients were excluded from clinical trials.
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.
Hyponatremia
Moderate:
aliskiren
Aliskiren has a moderate potential interaction with Hyponatremia.
Symptomatic hypotension may occur after treatment initiation with aliskiren in patients with marked volume depletion, salt depletion, or with combined use of aliskiren and other agents acting on the renin-angiotensin-aldosterone system. It is recommended to correct the volume or salt depletion before administering aliskiren. Close monitoring 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:
aliskiren
Aliskiren has a moderate potential interaction with Renal Dysfunction.
Renal function should be monitored periodically in patients treated with aliskiren, as changes can occur including acute renal failure. Patients on aliskiren whose renal function may depend in part of the RAAS (renin-angiotensin-aldosterone system), such as patients with renal artery stenosis, severe heart failure, or postmyocardial infarction may be at higher risk for developing acute renal failure. Treatment should be discontinued in any patients who develop clinically significant decrease in renal function. Patients with renal impairment should be observed closely. The safety and effectiveness of aliskiren have not been established in patients with severe renal impairment (CrCl < 30 mL/min), as these patients were excluded from clinical trials.
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.
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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aliskiren
A total of 318 drugs are known to interact with aliskiren.
- Aliskiren is in the drug class renin inhibitors.
- Aliskiren is used to treat High Blood Pressure.
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.
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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