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Drug Interactions between Nuedexta and troglitazone

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

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Interactions between your drugs

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

  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
View all 6 references

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Moderate

quiNIDine troglitazone

Applies to: Nuedexta (dextromethorphan / quinidine) and troglitazone

MONITOR: Coadministration with troglitazone may decrease the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. The mechanism is accelerated clearance due to induction of CYP450 3A4 activity by troglitazone.

MANAGEMENT: Caution is advised if troglitazone must be used concomitantly with medications that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever troglitazone is added to or withdrawn from therapy.

References

  1. (2001) "Product Information. Rezulin (troglitazone)." Parke-Davis
  2. Kaplan B, Friedman G, Jacobs M, Viscuso R, Lyman N, DeFranco P, Bonomini L, Mulgaonkar SP (1998) "Potential interaction of troglitazone and cyclosporine." Transplantation, 65, p. 1399-400
  3. Burgess SJ, Singer GG, Brennan DC (1998) "Effect of troglitazone on cyclosporine whole blood levels." Transplantation, 66, p. 272
  4. Frantz RP, Nguyen TT (1998) "Rezulin (troglitazone) greatly increases cyclosporine metabolism." J Heart Lung Transplant, 17, p. 1037-8
  5. Terra SG, Washam JB, May DB (1998) "Comment: troglitazone drug interactions." Ann Pharmacother, 32, p. 1111
  6. Fraser CG, Fierro L (1998) "Comment: troglitazone." Ann Pharmacother, 32, p. 1111-2
  7. Park MH, Pelegrin D, Haug MT, Young JB (1998) "Troglitazone, a new antidiabetic agent, decreases cyclosporine level." J Heart Lung Transplant, 17, p. 1139-40
View all 7 references

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Moderate

dextromethorphan troglitazone

Applies to: Nuedexta (dextromethorphan / quinidine) and troglitazone

MONITOR: Coadministration with troglitazone may decrease the plasma concentrations of drugs that are substrates of the CYP450 3A4 isoenzyme. The mechanism is accelerated clearance due to induction of CYP450 3A4 activity by troglitazone.

MANAGEMENT: Caution is advised if troglitazone must be used concomitantly with medications that undergo metabolism by CYP450 3A4, particularly those with a narrow therapeutic range. Dosage adjustments as well as clinical and laboratory monitoring may be appropriate for some drugs whenever troglitazone is added to or withdrawn from therapy.

References

  1. (2001) "Product Information. Rezulin (troglitazone)." Parke-Davis
  2. Kaplan B, Friedman G, Jacobs M, Viscuso R, Lyman N, DeFranco P, Bonomini L, Mulgaonkar SP (1998) "Potential interaction of troglitazone and cyclosporine." Transplantation, 65, p. 1399-400
  3. Burgess SJ, Singer GG, Brennan DC (1998) "Effect of troglitazone on cyclosporine whole blood levels." Transplantation, 66, p. 272
  4. Frantz RP, Nguyen TT (1998) "Rezulin (troglitazone) greatly increases cyclosporine metabolism." J Heart Lung Transplant, 17, p. 1037-8
  5. Terra SG, Washam JB, May DB (1998) "Comment: troglitazone drug interactions." Ann Pharmacother, 32, p. 1111
  6. Fraser CG, Fierro L (1998) "Comment: troglitazone." Ann Pharmacother, 32, p. 1111-2
  7. Park MH, Pelegrin D, Haug MT, Young JB (1998) "Troglitazone, a new antidiabetic agent, decreases cyclosporine level." J Heart Lung Transplant, 17, p. 1139-40
View all 7 references

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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

  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
View all 4 references

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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

  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
View all 4 references

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Moderate

troglitazone food

Applies to: troglitazone

GENERALLY AVOID: Alcohol may cause hypoglycemia or hyperglycemia in patients with diabetes. Hypoglycemia most frequently occurs during acute consumption of alcohol. Even modest amounts can lower blood sugar significantly, especially when the alcohol is ingested on an empty stomach or following exercise. The mechanism involves inhibition of both gluconeogenesis as well as the counter-regulatory response to hypoglycemia. Episodes of hypoglycemia may last for 8 to 12 hours after ethanol ingestion. By contrast, chronic alcohol abuse can cause impaired glucose tolerance and hyperglycemia. Moderate alcohol consumption generally does not affect blood glucose levels in patients with well controlled diabetes. A disulfiram-like reaction (e.g., flushing, headache, and nausea) to alcohol has been reported frequently with the use of chlorpropamide and very rarely with other sulfonylureas.

MANAGEMENT: Patients with diabetes should avoid consuming alcohol if their blood glucose is not well controlled, or if they have hypertriglyceridemia, neuropathy, or pancreatitis. Patients with well controlled diabetes should limit their alcohol intake to one drink daily for women and two drinks daily for men (1 drink = 5 oz wine, 12 oz beer, or 1.5 oz distilled spirits) in conjunction with their normal meal plan. Alcohol should not be consumed on an empty stomach or following exercise.

References

  1. Jerntorp P, Almer LO (1981) "Chlorpropamide-alcohol flushing in relation to macroangiopathy and peripheral neuropathy in non-insulin dependent diabetes." Acta Med Scand, 656, p. 33-6
  2. Jerntorp P, Almer LO, Holin H, et al. (1983) "Plasma chlorpropamide: a critical factor in chlorpropamide-alcohol flush." Eur J Clin Pharmacol, 24, p. 237-42
  3. Barnett AH, Spiliopoulos AJ, Pyke DA, et al. (1983) "Metabolic studies in chlorpropamide-alcohol flush positive and negative type 2 (non-insulin dependent) diabetic patients with and without retinopathy." Diabetologia, 24, p. 213-5
  4. Hartling SG, Faber OK, Wegmann ML, Wahlin-Boll E, Melander A (1987) "Interaction of ethanol and glipizide in humans." Diabetes Care, 10, p. 683-6
  5. (2002) "Product Information. Diabinese (chlorpropamide)." Pfizer U.S. Pharmaceuticals
  6. (2002) "Product Information. Glucotrol (glipizide)." Pfizer U.S. Pharmaceuticals
  7. "Product Information. Diabeta (glyburide)." Hoechst Marion-Roussel Inc, Kansas City, MO.
  8. Skillman TG, Feldman JM (1981) "The pharmacology of sulfonylureas." Am J Med, 70, p. 361-72
  9. (2002) "Position Statement: evidence-based nutrition principles and recommendations for the treatment and prevention of diabetes related complications. American Diabetes Association." Diabetes Care, 25(Suppl 1), S50-S60
  10. Cerner Multum, Inc. "UK Summary of Product Characteristics."
View all 10 references

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Therapeutic duplication warnings

No 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.

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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.

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