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Drug Interaction Report

8 potential interactions and/or warnings found for the following 3 drugs:

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Interactions between your drugs

Major

nortriptyline escitalopram

Applies to: nortriptyline, escitalopram

MONITOR CLOSELY: Concomitant use of agents with serotonergic activity including selective serotonin reuptake inhibitors, tricyclic antidepressants, and other antidepressants may potentiate the risk of serotonin syndrome, which is a rare but serious and potentially fatal condition thought to result from hyperstimulation of brainstem 5-HT1A and 2A receptors. Symptoms of the serotonin syndrome may include mental status changes such as irritability, altered consciousness, confusion, hallucination, and coma; autonomic dysfunction such as tachycardia, hyperthermia, diaphoresis, shivering, blood pressure lability, and mydriasis; neuromuscular abnormalities such as hyperreflexia, myoclonus, tremor, rigidity, and ataxia; and gastrointestinal symptoms such as abdominal cramping, nausea, vomiting, and diarrhea.

MONITOR CLOSELY: Escitalopram can cause dose-dependent prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval including tricyclic antidepressants and other antidepressants (e.g., trazodone) may result in additive effects and increased risk of ventricular arrhythmias such as torsade de pointes and sudden death. In a double-blind, placebo-controlled ECG study consisting of 113 healthy subjects, the change from baseline in QTc (Fridericia-corrected) was 4.3 msec for escitalopram 10 mg/day and 10.7 msec for the supratherapeutic dosage of 30 mg/day. Based on the established exposure-response relationship, the predicted QTc change from placebo under the Cmax for 20 mg/day is 6.6 msec. Cases of QT interval prolongation and torsade de pointes have been reported during postmarketing use. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). Also, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: In general, the concomitant use of multiple serotonergic agents should be avoided if possible, or otherwise approached with caution if potential benefit is deemed to outweigh the risk. Patients should be closely monitored for symptoms of the serotonin syndrome during treatment. Particular caution is advised when increasing the dosages of these agents. If serotonin syndrome develops or is suspected during the course of therapy, all serotonergic agents should be discontinued immediately and supportive care rendered as necessary. Moderately ill patients may also benefit from the administration of a serotonin antagonist (e.g., cyproheptadine, chlorpromazine). Severe cases should be managed under consultation with a toxicologist and may require sedation, neuromuscular paralysis, intubation, and mechanical ventilation in addition to the other measures. Due to the potential for additive effects on the QT interval, ECG monitoring may also be appropriate when escitalopram is used with tricyclic antidepressants or other antidepressants like trazodone. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References

  1. Nierenberg DW, Semprebon M. The central nervous system serotonin syndrome. Clin Pharmacol Ther. 1993;53:84-8.
  2. Metz A. Interaction between fluoxetine and buspirone. Can J Psychiatry. 1990;35:722-3.
  3. Goldberg RJ, Huk M. Serotonin syndrome from trazodone and buspirone. Psychosomatics. 1992;33:235-6.
  4. Sternbach H. The serotonin syndrome. Am J Psychiatry. 1991;148:705-13.
  5. Ciraulo DA, Shader RI. Fluoxetine drug-drug interactions. II. J Clin Psychopharmacol. 1990;10:213-7.
  6. Ciraulo DA, Shader RI. Fluoxetine drug-drug interactions: I. Antidepressants and antipsychotics. J Clin Psychopharmacol. 1990;10:48-50.
  7. Product Information. Zoloft (sertraline). Roerig Division. 2001;PROD.
  8. Product Information. Prozac (fluoxetine). Dista Products Company. 2001;PROD.
  9. Insel TR, Roy BF, Cohen RM, Murphy DL. Possible development of the serotonin syndrome in man. Am J Psychiatry. 1982;139:954-5.
  10. Gilman AG, eds., Nies AS, Rall TW, Taylor P. Goodman and Gilman's the Pharmacological Basis of Therapeutics. New York, NY: Pergamon Press Inc. 1990.
  11. Product Information. Paxil (paroxetine). GlaxoSmithKline. 2001;PROD.
  12. Ruiz F. Fluoxetine and the serotonin syndrome. Ann Emerg Med. 1994;24:983-5.
  13. Product Information. Luvox (fluvoxamine). Solvay Pharmaceuticals Inc. 2001;PROD.
  14. Reeves RR, Bullen JA. Serotonin syndrome produced by paroxetine and low-dose trazodone. Psychosomatics. 1995;36:159-60.
  15. Harvey AT, Preskorn SH. Interactions of serotonin reuptake inhibitors with tricyclic antidepressants. Arch Gen Psychiatry. 1995;52:783-4.
  16. Fischer P. Serotonin syndrome in the elderly after antidepressive monotherapy. J Clin Psychopharmacol. 1995;15:440-2.
  17. Corkeron MA. Serotonin syndrome - a potentially fatal complication of antidepressant therapy. Med J Aust. 1995;163:481-2.
  18. George TP, Godleski LS. Possible serotonin syndrome with trazodone addition to fluoxetine. Biol Psychiatry. 1996;39:384-5.
  19. Skop BP, Finkelstein JA, Mareth TR, Magoon MR, Brown TM. The serotonin syndrome associated wtih paroxetine, an over-the-counter cold remedy, and vascular disease. Am J Emerg Med. 1994;12:642-4.
  20. John L, Perreault MM, Tao T, Blew PG. Serotonin syndrome associated with nefazodone and paroxetine. Ann Emerg Med. 1997;29:287-9.
  21. Mills KC. Serotonin syndrome: A clinical update. Crit Care Clin. 1997;13:763.
  22. Bhatara VS, Magnus RD, Paul KL, Preskorn SH. Serotonin syndrome induced by venlafaxine and fluoxetine: a case study in polypharmacy and potential pharmacodynamic and pharmacokinetic mechanisms. Ann Pharmacother. 1998;32:432-6.
  23. Product Information. Celexa (citalopram). Forest Pharmaceuticals. 2001;PROD.
  24. Chan BSH, Graudins A, Whyte IM, Dawson AH, Braitberg G, Duggin GG. Serotonin syndrome resulting from drug interactions. Med J Aust. 1998;169:523-5.
  25. Manos GH. Possible serotonin syndrome associated with buspirone added to fluoxetine. Ann Pharmacother. 2000;34:871-4.
  26. Nijhawan PK, Katz G, Winter S. Psychiatric illness and the serotonin syndrome: an emerging adverse drug effect leading to intensive care unit admission. Crit Care Med. 1996;24:1086-9.
  27. Margolese HC, Chouinard G. Serotonin syndrome from addition of low-dose trazodone to nefazodone. Am J Psychiatry. 2000;157:1022.
  28. Mackay FJ, Dunn NR, Mann RD. Antidepressants and the serotonin syndrome in general practice. Br J Gen Pract. 1999;49:871-4.
  29. Smith DL, Wenegrat BG. A case report of serotonin syndrome associated with combined nefazodone and fluoxetine. J Clin Psychiatry. 2000;61:146.
  30. Product Information. Lexapro (escitalopram). Forest Pharmaceuticals. 2002.
  31. Dougherty JA, Young H, Shafi T. Serotonin syndrome induced by amitriptyline, meperidine, and venlafaxine. Ann Pharmacother. 2002;36:1647-1648.
  32. Martin TG. Serotonin syndrome. Ann Emerg Med. 1996;28:520-6.
  33. Lane R, Baldwin D. Selective serotonin reuptake inhibitor--induced serotonin syndrome: review. J Clin Psychopharmacol. 1997;17:208-21.
  34. Paruchuri P, Godkar D, Anandacoomarswamy D, Sheth K, Niranjan S. Rare case of serotonin syndrome with therapeutic doses of paroxetine. Am J Ther. 2006;13:550-552.
  35. Castro VM, Clements CC, Murphy SN, et al. QT interval and antidepressant use: a cross sectional study of electronic health records. BMJ. 2013;346:f288.
View all 35 references

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Moderate

nortriptyline diazePAM

Applies to: nortriptyline, diazepam

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring 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. Hamilton MJ, Bush M, Smith P, Peck AW. The effects of bupropion, a new antidepressant drug, and diazepam, and their interaction in man. Br J Clin Pharmacol. 1982;14:791-7.
  2. Stambaugh JE, Lane C. Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination. Cancer Invest. 1983;1:111-7.
  3. Sotaniemi EA, Anttila M, Rautio A, et al. Propranolol and sotalol metabolism after a drinking party. Clin Pharmacol Ther. 1981;29:705-10.
  4. Grabowski BS, Cady WJ, Young WW, Emery JF. Effects of acute alcohol administration on propranolol absorption. Int J Clin Pharmacol Ther Toxicol. 1980;18:317-9.
  5. Lemberger L, Rowe H, Bosomworth JC, Tenbarge JB, Bergstrom RF. The effect of fluoxetine on the pharmacokinetics and psychomotor responses of diazepam. Clin Pharmacol Ther. 1988;43:412-9.
  6. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM. Diazepam actions and plasma concentrations following ethanol ingestion. Eur J Clin Pharmacol. 1977;11:345-9.
  7. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI. Benzodiazepine overdosage: plasma concentrations and clinical outcome. Psychopharmacology (Berl). 1981;73:381-3.
  8. Naylor GJ, McHarg A. Profound hypothermia on combined lithium carbonate and diazepam treatment. Br Med J. 1977;2:22.
  9. Stovner J, Endresen R. Intravenous anaesthesia with diazepam. Acta Anaesthesiol Scand. 1965;24:223-7.
  10. Driessen JJ, Vree TB, Booij LH, van der Pol FM, Crul JF. Effect of some benzodiazepines on peripheral neuromuscular function in the rat in-vitro hemidiaphragm preparation. J Pharm Pharmacol. 1984;36:244-7.
  11. Feldman SA, Crawley BE. Interaction of diazepam with the muscle-relaxant drugs. Br Med J. 1970;1:336-8.
  12. Ochs HR, Greenblatt DJ, Verburg-Ochs B. Propranolol interactions with diazepam, lorazepam and alprazolam. Clin Pharmacol Ther. 1984;36:451-5.
  13. Desager JP, Hulhoven R, Harvengt C, Hermann P, Guillet P, Thiercelin JF. Possible interactions between zolpidem, a new sleep inducer and chlorpromazine, a phenothiazine neuroleptic. Psychopharmacology (Berl). 1988;96:63-6.
  14. Tverskoy M, Fleyshman G, Ezry J, Bradley EL, Jr Kissin I. Midazolam-morphine sedative interaction in patients. Anesth Analg. 1989;68:282-5.
  15. Product Information. Iopidine (apraclonidine ophthalmic). Alcon Laboratories Inc. PROD.
  16. Greiff JMC, Rowbotham D. Pharmacokinetic drug interactions with gastrointestinal motility modifying agents. Clin Pharmacokinet. 1994;27:447-61.
  17. Greb WH, Buscher G, Dierdorf HD, Koster FE, Wolf D, Mellows G. The effect of liver enzyme inhibition by cimetidine and enzyme induction by phenobarbitone on the pharmacokinetics of paroxetine. Acta Psychiatr Scand. 1989;80 Suppl:95-8.
  18. Markowitz JS, Wells BG, Carson WH. Interactions between antipsychotic and antihypertensive drugs. Ann Pharmacother. 1995;29:603-9.
  19. Product Information. Ultram (tramadol). McNeil Pharmaceutical. 2001;PROD.
  20. Product Information. Artane (trihexyphenidyl). Lederle Laboratories. 2001;PROD.
  21. Product Information. Ultiva (remifentanil). Mylan Institutional (formally Bioniche Pharma USA Inc). 2001;PROD.
  22. Product Information. Seroquel (quetiapine). Astra-Zeneca Pharmaceuticals. 2001;PROD.
  23. Product Information. Meridia (sibutramine). Knoll Pharmaceutical Company. 2001;PROD.
  24. Product Information. Tasmar (tolcapone). Valeant Pharmaceuticals. 2001;PROD.
  25. Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med. 1998;158:2200-11.
  26. Product Information. Precedex (dexmedetomidine). Abbott Pharmaceutical. 2001;PROD.
  27. Product Information. Trileptal (oxcarbazepine). Novartis Pharmaceuticals. 2001;PROD.
  28. Ferslew KE, Hagardorn AN, McCormick WF. A fatal interaction of methocarbamol and ethanol in an accidental poisoning. J Forensic Sci. 1990;35:477-82.
  29. Plushner SL. Valerian: valeriana officinalis. Am J Health Syst Pharm. 2000;57:328-35.
  30. Product Information. Xatral (alfuzosin). Sanofi-Synthelabo Canada Inc. 2002.
  31. Product Information. Lexapro (escitalopram). Forest Pharmaceuticals. 2002.
  32. Cerner Multum, Inc. UK Summary of Product Characteristics.
  33. Cerner Multum, Inc. Australian Product Information.
  34. Product Information. Fycompa (perampanel). Eisai Inc. 2012.
  35. Product Information. Belsomra (suvorexant). Merck & Co., Inc. 2014.
  36. Product Information. Rexulti (brexpiprazole). Otsuka American Pharmaceuticals Inc. 2015.
View all 36 references

Switch to consumer interaction data

Moderate

diazePAM escitalopram

Applies to: diazepam, escitalopram

MONITOR: Central nervous system- and/or respiratory-depressant effects may be additively or synergistically increased in patients taking multiple drugs that cause these effects, especially in elderly or debilitated patients. Sedation and impairment of attention, judgment, thinking, and psychomotor skills may increase.

MANAGEMENT: During concomitant use of these drugs, patients should be monitored for potentially excessive or prolonged CNS and respiratory depression. Cautious dosage titration may be required, particularly at treatment initiation. Ambulatory patients should be counseled to avoid hazardous activities requiring 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. Hamilton MJ, Bush M, Smith P, Peck AW. The effects of bupropion, a new antidepressant drug, and diazepam, and their interaction in man. Br J Clin Pharmacol. 1982;14:791-7.
  2. Stambaugh JE, Lane C. Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination. Cancer Invest. 1983;1:111-7.
  3. Sotaniemi EA, Anttila M, Rautio A, et al. Propranolol and sotalol metabolism after a drinking party. Clin Pharmacol Ther. 1981;29:705-10.
  4. Grabowski BS, Cady WJ, Young WW, Emery JF. Effects of acute alcohol administration on propranolol absorption. Int J Clin Pharmacol Ther Toxicol. 1980;18:317-9.
  5. Lemberger L, Rowe H, Bosomworth JC, Tenbarge JB, Bergstrom RF. The effect of fluoxetine on the pharmacokinetics and psychomotor responses of diazepam. Clin Pharmacol Ther. 1988;43:412-9.
  6. MacLeod SM, Giles HG, Patzalek G, Thiessen JJ, Sellers EM. Diazepam actions and plasma concentrations following ethanol ingestion. Eur J Clin Pharmacol. 1977;11:345-9.
  7. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI. Benzodiazepine overdosage: plasma concentrations and clinical outcome. Psychopharmacology (Berl). 1981;73:381-3.
  8. Naylor GJ, McHarg A. Profound hypothermia on combined lithium carbonate and diazepam treatment. Br Med J. 1977;2:22.
  9. Stovner J, Endresen R. Intravenous anaesthesia with diazepam. Acta Anaesthesiol Scand. 1965;24:223-7.
  10. Driessen JJ, Vree TB, Booij LH, van der Pol FM, Crul JF. Effect of some benzodiazepines on peripheral neuromuscular function in the rat in-vitro hemidiaphragm preparation. J Pharm Pharmacol. 1984;36:244-7.
  11. Feldman SA, Crawley BE. Interaction of diazepam with the muscle-relaxant drugs. Br Med J. 1970;1:336-8.
  12. Ochs HR, Greenblatt DJ, Verburg-Ochs B. Propranolol interactions with diazepam, lorazepam and alprazolam. Clin Pharmacol Ther. 1984;36:451-5.
  13. Desager JP, Hulhoven R, Harvengt C, Hermann P, Guillet P, Thiercelin JF. Possible interactions between zolpidem, a new sleep inducer and chlorpromazine, a phenothiazine neuroleptic. Psychopharmacology (Berl). 1988;96:63-6.
  14. Tverskoy M, Fleyshman G, Ezry J, Bradley EL, Jr Kissin I. Midazolam-morphine sedative interaction in patients. Anesth Analg. 1989;68:282-5.
  15. Product Information. Iopidine (apraclonidine ophthalmic). Alcon Laboratories Inc. PROD.
  16. Greiff JMC, Rowbotham D. Pharmacokinetic drug interactions with gastrointestinal motility modifying agents. Clin Pharmacokinet. 1994;27:447-61.
  17. Greb WH, Buscher G, Dierdorf HD, Koster FE, Wolf D, Mellows G. The effect of liver enzyme inhibition by cimetidine and enzyme induction by phenobarbitone on the pharmacokinetics of paroxetine. Acta Psychiatr Scand. 1989;80 Suppl:95-8.
  18. Markowitz JS, Wells BG, Carson WH. Interactions between antipsychotic and antihypertensive drugs. Ann Pharmacother. 1995;29:603-9.
  19. Product Information. Ultram (tramadol). McNeil Pharmaceutical. 2001;PROD.
  20. Product Information. Artane (trihexyphenidyl). Lederle Laboratories. 2001;PROD.
  21. Product Information. Ultiva (remifentanil). Mylan Institutional (formally Bioniche Pharma USA Inc). 2001;PROD.
  22. Product Information. Seroquel (quetiapine). Astra-Zeneca Pharmaceuticals. 2001;PROD.
  23. Product Information. Meridia (sibutramine). Knoll Pharmaceutical Company. 2001;PROD.
  24. Product Information. Tasmar (tolcapone). Valeant Pharmaceuticals. 2001;PROD.
  25. Miller LG. Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med. 1998;158:2200-11.
  26. Product Information. Precedex (dexmedetomidine). Abbott Pharmaceutical. 2001;PROD.
  27. Product Information. Trileptal (oxcarbazepine). Novartis Pharmaceuticals. 2001;PROD.
  28. Ferslew KE, Hagardorn AN, McCormick WF. A fatal interaction of methocarbamol and ethanol in an accidental poisoning. J Forensic Sci. 1990;35:477-82.
  29. Plushner SL. Valerian: valeriana officinalis. Am J Health Syst Pharm. 2000;57:328-35.
  30. Product Information. Xatral (alfuzosin). Sanofi-Synthelabo Canada Inc. 2002.
  31. Product Information. Lexapro (escitalopram). Forest Pharmaceuticals. 2002.
  32. Cerner Multum, Inc. UK Summary of Product Characteristics.
  33. Cerner Multum, Inc. Australian Product Information.
  34. Product Information. Fycompa (perampanel). Eisai Inc. 2012.
  35. Product Information. Belsomra (suvorexant). Merck & Co., Inc. 2014.
  36. Product Information. Rexulti (brexpiprazole). Otsuka American Pharmaceuticals Inc. 2015.
View all 36 references

Switch to consumer interaction data

No other interactions were found between your selected drugs. However, this does not necessarily mean no other interactions exist. Always consult your healthcare provider.

Drug and food interactions

Moderate

diazePAM food

Applies to: diazepam

GENERALLY AVOID: Acute alcohol ingestion may potentiate the CNS depression and other CNS effects of many benzodiazepines. Tolerance may develop with chronic ethanol use. The mechanism may be decreased clearance of the benzodiazepines because of CYP450 hepatic enzyme inhibition. Also, it has been suggested that the cognitive deficits induced by benzodiazepines may be increased in patients who chronically consume large amounts of alcohol.

MONITOR: Grapefruit juice may increase the plasma concentrations of orally administered drugs that are substrates of the CYP450 3A4 isoenzyme. However, the interaction seems to affect primarily those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability), presumably due to the fact that grapefruit juice inhibits intestinal rather than hepatic CYP450 3A4. Because pharmacokinetic interactions involving grapefruit juice are often subject to a high degree of interpatient variability, the extent to which a given patient may be affected is difficult to predict.

MANAGEMENT: Patients should be advised to avoid alcohol during benzodiazepine therapy. Patients who regularly consume grapefruit or grapefruit juice should be monitored for adverse effects and altered plasma concentrations of drugs that undergo significant presystemic metabolism by CYP450 3A4. Grapefruit and grapefruit juice should be avoided if an interaction is suspected. Orange juice is not expected to interact with these drugs.

References

  1. Edgar B, Bailey D, Bergstrand R, et al. Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics on felodipine and its potential clinical relevance. Eur J Clin Pharmacol. 1992;42:313-7.
  2. Jonkman JH, Sollie FA, Sauter R, Steinijans VW. The influence of caffeine on the steady-state pharmacokinetics of theophylline. Clin Pharmacol Ther. 1991;49:248-55.
  3. Product Information. Valium (diazepam). Roche Laboratories. 2002;PROD.
  4. Bailey DG, Arnold JM, Munoz C, Spence JD. Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin. Clin Pharmacol Ther. 1993;53:637-42.
  5. Bailey DG, Arnold JMO, Spence JD. Grapefruit juice and drugs - how significant is the interaction. Clin Pharmacokinet. 1994;26:91-8.
  6. Product Information. Doral (quazepam). Wallace Laboratories. 2001;PROD.
  7. Sigusch H, Hippius M, Henschel L, Kaufmann K, Hoffmann A. Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation. Pharmazie. 1994;49:522-4.
  8. Bailey DG, Arnold JM, Strong HA, Munoz C, Spence JD. Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics. Clin Pharmacol Ther. 1993;54:589-94.
  9. Yamreudeewong W, Henann NE, Fazio A, Lower DL, Cassidy TG. Drug-food interactions in clinical practice. J Fam Pract. 1995;40:376-84.
  10. Grapefruit juice interactions with drugs. Med Lett Drugs Ther. 1995;37:73-4.
  11. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ. Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice. Clin Pharmacol Ther. 1995;58:127-31.
  12. Min DI, Ku YM, Geraets DR, Lee HC. Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers. J Clin Pharmacol. 1996;36:469-76.
  13. Majeed A, Kareem A. Effect of grapefruit juice on cyclosporine pharmacokinetics. Pediatr Nephrol. 1996;10:395.
  14. Clifford CP, Adams DA, Murray S, Taylor GW, Wilkins MR, Boobis AR, Davies DS. Pharmacokinetic and cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice. Br J Clin Pharmacol. 1996;42:p662.
  15. Josefsson M, Zackrisson AL, Ahlner J. Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers. Eur J Clin Pharmacol. 1996;51:189-93.
  16. Kantola T, Kivisto KT, Neuvonen PJ. Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid. Clin Pharmacol Ther. 1998;63:397-402.
  17. Ozdemir M, Aktan Y, Boydag BS, Cingi MI, Musmul A. Interaction between grapefruit juice and diazepam in humans. Eur J Drug Metab Pharmacokinet. 1998;23:55-9.
  18. Bailey DG, Malcolm J, Arnold O, Spence JD. Grapefruit juice-drug interactions. Br J Clin Pharmacol. 1998;46:101-10.
  19. Bailey DG, Kreeft JH, Munoz C, Freeman DJ, Bend JR. Grapefruit juice felodipine interaction: Effect of naringin and 6',7'-dihydroxybergamottin in humans. Clin Pharmacol Ther. 1998;64:248-56.
  20. Garg SK, Kumar N, Bhargava VK, Prabhakar SK. Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy. Clin Pharmacol Ther. 1998;64:286-8.
  21. Lilja JJ, Kivisto KT, Neuvonen PJ. Grapefruit juice-simvastatin interaction: Effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors. Clin Pharmacol Ther. 1998;64:477-83.
  22. Fuhr U, Maier-Bruggemann A, Blume H, et al. Grapefruit juice increases oral nimodipine bioavailability. Int J Clin Pharmacol Ther. 1998;36:126-32.
  23. Lilja JJ, Kivisto KT, Neuvonen PJ. Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin. Clin Pharmacol Ther. 1999;66:118-27.
  24. Eagling VA, Profit L, Back DJ. Inhibition of the CYP3A4-mediated metabolism and P-glycoprotein-mediated transport of the HIV-I protease inhibitor saquinavir by grapefruit juice components. Br J Clin Pharmacol. 1999;48:543-52.
  25. Damkier P, Hansen LL, Brosen K. Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine. Br J Clin Pharmacol. 1999;48:829-38.
  26. Lee AJ, Chan WK, Harralson AF, Buffum J, Bui BCC. The effects of grapefruit juice on sertraline metabolism: An in vitro and in vivo study. Clin Ther. 1999;21:1890-9.
  27. Dresser GK, Spence JD, Bailey DG. Pharmacokinetic-pharmacodynamic consequences and clinical relevance of cytochrome P450 3A4 inhibition. Clin Pharmacokinet. 2000;38:41-57.
  28. Gunston GD, Mehta U. Potentially serious drug interactions with grapefruit juice. S Afr Med J. 2000;90:41.
  29. Takanaga H, Ohnishi A, Maatsuo H, et al. Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model. Br J Clin Pharmacol. 2000;49:49-58.
  30. Libersa CC, Brique SA, Motte KB, et al. Dramatic inhibition of amiodarone metabolism induced by grapefruit juice. Br J Clin Pharmacol. 2000;49:373-8.
  31. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR. Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients. Clin Pharmacol Ther. 2000;68:468-77.
  32. Zaidenstein R, Soback S, Gips M, Avni B, Dishi V, Weissgarten Y, Golik A, Scapa E. Effect of grapefruit juice on the pharmacokinetics of losartan and its active metabolite E3174 in healthy volunteers. Ther Drug Monit. 2001;23:369-73.
  33. Sato J, Nakata H, Owada E, Kikuta T, Umetsu M, Ito K. Influence of usual intake of dietary caffeine on single-dose kinetics of theophylline in healthy human subjects. Eur J Clin Pharmacol. 1993;44:295-8.
  34. Flanagan D. Understanding the grapefruit-drug interaction. Gen Dent. 2005;53:282-5; quiz 286.
View all 34 references

Switch to consumer interaction data

Moderate

escitalopram food

Applies to: escitalopram

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. Evaluation of possible interactions between ethanol and trazodone or amitriptyline. Neuropsychobiology. 1986;15:31-7.
  2. Gilman AG, eds., Nies AS, Rall TW, Taylor P. Goodman and Gilman's the Pharmacological Basis of Therapeutics. New York, NY: Pergamon Press Inc. 1990.
  3. Product Information. Fycompa (perampanel). Eisai Inc. 2012.
  4. Product Information. Rexulti (brexpiprazole). Otsuka American Pharmaceuticals Inc. 2015.
View all 4 references

Switch to consumer interaction data

Moderate

nortriptyline food

Applies to: nortriptyline

GENERALLY AVOID: Concomitant use of ethanol and a tricyclic antidepressant (TCA) may result altered TCA plasma levels and efficacy, and additive impairment of motor skills, especially driving skills. Acute ethanol ingestion may inhibit TCA metabolism, while chronic ingestion of large amounts of ethanol may induce hepatic TCA metabolism.

MANAGEMENT: Patients should be advised to avoid alcohol during TCA therapy. Alcoholics who have undergone detoxification should be monitored for decreased TCA efficacy. Dosage adjustments may be required.

References

  1. Dorian P, Sellers EM, Reed KL, et al. Amitriptyline and ethanol: pharmacokinetic and pharmacodynamic interaction. Eur J Clin Pharmacol. 1983;25:325-31.
  2. Warrington SJ, Ankier SI, Turner P. Evaluation of possible interactions between ethanol and trazodone or amitriptyline. Neuropsychobiology. 1986;15:31-7.
  3. Sandoz M, Vandel S, Vandel B, Bonin B, Allers G, Volmat R. Biotransformation of amitriptyline in alcoholic depressive patients. Eur J Clin Pharmacol. 1983;24:615-21.
  4. Ciraulo DA, Barnhill JG, Jaffe JH. Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers. Clin Pharmacol Ther. 1988;43:509-18.
  5. Seppala T, Linnoila M, Elonen E, Mattila MJ, Makl M. Effect of tricyclic antidepressants and alcohol on psychomotor skills related to driving. Clin Pharmacol Ther. 1975;17:515-22.
  6. Ciraulo DA, Barnhill JG, Jaffe JH, Ciraulo AM, Tarmey MF. Intravenous pharmacokinetics of 2-hydroxyimipramine in alcoholics and normal controls. J Stud Alcohol. 1990;51:366-72.
  7. Ciraulo DA, Alderson LM, Chapron DJ, Jaffe JH, Subbarao B, Kramer PA. Imipramine disposition in alcoholics. J Clin Psychopharmacol. 1982;2:2-7.
View all 7 references

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Minor

diazePAM food

Applies to: diazepam

One study has reported a 22% reduction in diazepam plasma levels when coadministered with caffeine. The exact mechanism of this interaction has not been specified. Physicians and patients should be aware that changes to caffeine consumption habits may impact the efficacy of diazepam therapy.

References

  1. Ghoneim MM, Hinrichs JV, Chiang CK, Loke WH. Pharmacokinetic and pharmacodynamic interactions between caffeine and diazepam. J Clin Psychopharmacol. 1986;6:75-80.

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Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Antidepressants

Therapeutic duplication

The recommended maximum number of medicines in the 'antidepressants' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'antidepressants' category:

  • escitalopram
  • nortriptyline

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.


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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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Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.