Drug Interaction Report
8 potential interactions and/or warnings found for the following 2 drugs:
- deutivacaftor / tezacaftor / vanzacaftor
- dextromethorphan / quinidine
Interactions between your drugs
quiNIDine dextromethorphan
Applies to: dextromethorphan / quinidine, 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)
- 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
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Cerner Multum, Inc. "Australian Product Information."
- (2010) "Product Information. Nuedexta (dextromethorphan-quinidine)." Avanir Pharmaceuticals, Inc
quiNIDine tezacaftor
Applies to: dextromethorphan / quinidine, deutivacaftor / tezacaftor / vanzacaftor
MONITOR: Coadministration with tezacaftor and/or deutivacaftor may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) efflux transporter. The mechanism is decreased clearance via inhibition of the transporter by tezacaftor and/or deutivacaftor. In study subjects, digoxin (single 0.5 mg dose) systemic exposure (AUC) increased by 1.3-fold when it was administered with tezacaftor 25 mg and ivacaftor 50 mg daily. No pharmacokinetic data are available for deutivacaftor, but increased exposures of certain P-gp substrates are expected according to prescribing information.
MANAGEMENT: Caution is advised when tezacaftor and/or deutivacaftor are used with drugs that are P-gp substrates, particularly those where minimal concentration changes may lead to serious adverse reactions.
References (6)
- (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2020) "Product Information. KAFTRIO (elexacaftor/ivacaftor/tezacaftor)." VERTEX PHARMACEUTICALS (IRELAND) LIMITED
- (2023) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2024) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals Australia Pty Ltd
- (2023) "Product Information. Kaftrio (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals (Europe) Ltd
- (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals
quiNIDine deutivacaftor
Applies to: dextromethorphan / quinidine, deutivacaftor / tezacaftor / vanzacaftor
MONITOR: Coadministration with tezacaftor and/or deutivacaftor may increase the plasma concentrations of drugs that are substrates of the P-glycoprotein (P-gp) efflux transporter. The mechanism is decreased clearance via inhibition of the transporter by tezacaftor and/or deutivacaftor. In study subjects, digoxin (single 0.5 mg dose) systemic exposure (AUC) increased by 1.3-fold when it was administered with tezacaftor 25 mg and ivacaftor 50 mg daily. No pharmacokinetic data are available for deutivacaftor, but increased exposures of certain P-gp substrates are expected according to prescribing information.
MANAGEMENT: Caution is advised when tezacaftor and/or deutivacaftor are used with drugs that are P-gp substrates, particularly those where minimal concentration changes may lead to serious adverse reactions.
References (6)
- (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2020) "Product Information. KAFTRIO (elexacaftor/ivacaftor/tezacaftor)." VERTEX PHARMACEUTICALS (IRELAND) LIMITED
- (2023) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2024) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals Australia Pty Ltd
- (2023) "Product Information. Kaftrio (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals (Europe) Ltd
- (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals
Drug and food interactions
quiNIDine food
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
dextromethorphan food
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 American Pharmaceuticals Inc
tezacaftor food
Applies to: deutivacaftor / tezacaftor / vanzacaftor
GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of tezacaftor, deutivacaftor, and vanzacaftor. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In general, the effect of grapefruit juice is concentration-, dose- and preparation- dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. The risk and/or severity of serious side effects such as liver damage may be increased.
ADJUST DOSING INTERVAL: Administration with fat-containing food may increase the oral bioavailability of vanzacaftor and deutivacaftor. Administration with a fat containing meal increased vanzacaftor systemic exposure (AUC) by 4- (low-fat meal) to 6- (high-fat meal) fold. While deutivacaftor AUC increased approximately 3- (low-fat meal) to 4- (high-fat meal) fold, relative to administration in a fasting state. Tezacaftor exposure is not significantly affected by administration of fat-containing foods.
MANAGEMENT: Patients treated with tezacaftor, deutivacaftor, vanzacaftor -containing medications should avoid consumption of grapefruit juice and any food that contains grapefruit. To improve absorption, patients should be advised to take vanzacaftor and/or deutivacaftor containing medications with fat-containing foods such as eggs, avocados, nuts, meat, butter, peanut butter, cheese pizza, and whole-milk dairy products at approximately the same time of the day. A typical cystic fibrosis diet will satisfy this requirement.
References (6)
- (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2020) "Product Information. KAFTRIO (elexacaftor/ivacaftor/tezacaftor)." VERTEX PHARMACEUTICALS (IRELAND) LIMITED
- (2023) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2024) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals Australia Pty Ltd
- (2023) "Product Information. Kaftrio (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals (Europe) Ltd
- (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals
vanzacaftor food
Applies to: deutivacaftor / tezacaftor / vanzacaftor
GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of tezacaftor, deutivacaftor, and vanzacaftor. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In general, the effect of grapefruit juice is concentration-, dose- and preparation- dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. The risk and/or severity of serious side effects such as liver damage may be increased.
ADJUST DOSING INTERVAL: Administration with fat-containing food may increase the oral bioavailability of vanzacaftor and deutivacaftor. Administration with a fat containing meal increased vanzacaftor systemic exposure (AUC) by 4- (low-fat meal) to 6- (high-fat meal) fold. While deutivacaftor AUC increased approximately 3- (low-fat meal) to 4- (high-fat meal) fold, relative to administration in a fasting state. Tezacaftor exposure is not significantly affected by administration of fat-containing foods.
MANAGEMENT: Patients treated with tezacaftor, deutivacaftor, vanzacaftor -containing medications should avoid consumption of grapefruit juice and any food that contains grapefruit. To improve absorption, patients should be advised to take vanzacaftor and/or deutivacaftor containing medications with fat-containing foods such as eggs, avocados, nuts, meat, butter, peanut butter, cheese pizza, and whole-milk dairy products at approximately the same time of the day. A typical cystic fibrosis diet will satisfy this requirement.
References (6)
- (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2020) "Product Information. KAFTRIO (elexacaftor/ivacaftor/tezacaftor)." VERTEX PHARMACEUTICALS (IRELAND) LIMITED
- (2023) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2024) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals Australia Pty Ltd
- (2023) "Product Information. Kaftrio (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals (Europe) Ltd
- (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals
deutivacaftor food
Applies to: deutivacaftor / tezacaftor / vanzacaftor
GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of tezacaftor, deutivacaftor, and vanzacaftor. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In general, the effect of grapefruit juice is concentration-, dose- and preparation- dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. The risk and/or severity of serious side effects such as liver damage may be increased.
ADJUST DOSING INTERVAL: Administration with fat-containing food may increase the oral bioavailability of vanzacaftor and deutivacaftor. Administration with a fat containing meal increased vanzacaftor systemic exposure (AUC) by 4- (low-fat meal) to 6- (high-fat meal) fold. While deutivacaftor AUC increased approximately 3- (low-fat meal) to 4- (high-fat meal) fold, relative to administration in a fasting state. Tezacaftor exposure is not significantly affected by administration of fat-containing foods.
MANAGEMENT: Patients treated with tezacaftor, deutivacaftor, vanzacaftor -containing medications should avoid consumption of grapefruit juice and any food that contains grapefruit. To improve absorption, patients should be advised to take vanzacaftor and/or deutivacaftor containing medications with fat-containing foods such as eggs, avocados, nuts, meat, butter, peanut butter, cheese pizza, and whole-milk dairy products at approximately the same time of the day. A typical cystic fibrosis diet will satisfy this requirement.
References (6)
- (2019) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2020) "Product Information. KAFTRIO (elexacaftor/ivacaftor/tezacaftor)." VERTEX PHARMACEUTICALS (IRELAND) LIMITED
- (2023) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals
- (2024) "Product Information. Trikafta (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals Australia Pty Ltd
- (2023) "Product Information. Kaftrio (elexacaftor/ivacaftor/tezacaftor)." Vertex Pharmaceuticals (Europe) Ltd
- (2024) "Product Information. Alyftrek (deutivacaftor/tezacaftor/vanzacaftor)." Vertex Pharmaceuticals
Therapeutic duplication warnings
No duplication warnings were found for your selected drugs.
Therapeutic duplication warnings are only returned when drugs within the same group exceed the recommended therapeutic duplication maximum.
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. |
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