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Drug Interaction Report

3 potential interactions and/or warnings found for the following 2 drugs:

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Interactions between your drugs

Moderate

clonazePAM DULoxetine

Applies to: clonazepam, Cymbalta (duloxetine)

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

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Drug and food interactions

Moderate

DULoxetine food

Applies to: Cymbalta (duloxetine)

GENERALLY AVOID: Use of duloxetine in conjunction with chronic alcohol consumption may potentiate the risk of liver injury. Duloxetine alone can increase serum transaminase levels. In clinical trials, 0.3% of patients discontinued duloxetine due to liver transaminase elevations. The median time to detection was about two months. Three duloxetine-treated patients had liver injury as manifested by transaminase and bilirubin elevations, with evidence of obstruction. Substantial intercurrent ethanol use was present in each of these cases, which may have contributed to the abnormalities observed. Duloxetine does not appear to enhance the central nervous system effects of alcohol. When duloxetine and ethanol were administered several hours apart so that peak concentrations of each would coincide, duloxetine did not increase the impairment of mental and motor skills caused by alcohol.

MANAGEMENT: Due to the risk of liver injury, patients prescribed duloxetine should be counseled to avoid excessive use of alcohol. Duloxetine should generally not be prescribed to patients with substantial alcohol use.

References

  1. Product Information. Cymbalta (duloxetine). Lilly, Eli and Company. 2004.

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Moderate

clonazePAM food

Applies to: clonazepam

GENERALLY AVOID: Acute ethanol ingestion may potentiate the 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.

MANAGEMENT: Patients should be advised to avoid alcohol during benzodiazepine therapy.

References

  1. 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.
  2. Whiting B, Lawrence JR, Skellern GG, Meier J. Effect of acute alcohol intoxication on the metabolism and plasma kinetics of chlordiazepoxide. Br J Clin Pharmacol. 1979;7:95-100.
  3. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI. Benzodiazepine overdosage: plasma concentrations and clinical outcome. Psychopharmacology (Berl). 1981;73:381-3.
  4. Juhl RP, Van Thiel DH, Dittert LW, Smith RB. Alprazolam pharmacokinetics in alcoholic liver disease. J Clin Pharmacol. 1984;24:113-9.
  5. Ochs HR, Greenblatt DJ, Arendt RM, Hubbel W, Shader RI. Pharmacokinetic noninteraction of triazolam and ethanol. J Clin Psychopharmacol. 1984;4:106-7.
  6. Staak M, Raff G, Nusser W. Pharmacopsychological investigations concerning the combined effects of dipotassium clorazepate and ethanol. Int J Clin Pharmacol Biopharm. 1979;17:205-12.
  7. Nichols JM, Martin F, Kirkby KC. A comparison of the effect of lorazepam on memory in heavy and low social drinkers. Psychopharmacology (Berl). 1993;112:475-82.
View all 7 references

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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.

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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.

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