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Drug Interactions between acetaminophen / chlorpheniramine / dextromethorphan and stiripentol

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

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Interactions between your drugs

Moderate

chlorpheniramine dextromethorphan

Applies to: acetaminophen / chlorpheniramine / dextromethorphan and acetaminophen / chlorpheniramine / dextromethorphan

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 14 (1982): 791-7
  2. Stambaugh JE, Lane C "Analgesic efficacy and pharmacokinetic evaluation of meperidine and hydroxyzine, alone and in combination." Cancer Invest 1 (1983): 111-7
  3. Sotaniemi EA, Anttila M, Rautio A, et al. "Propranolol and sotalol metabolism after a drinking party." Clin Pharmacol Ther 29 (1981): 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 18 (1980): 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 43 (1988): 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 11 (1977): 345-9
  7. Divoll M, Greenblatt DJ, Lacasse Y, Shader RI "Benzodiazepine overdosage: plasma concentrations and clinical outcome." Psychopharmacology (Berl) 73 (1981): 381-3
  8. Naylor GJ, McHarg A "Profound hypothermia on combined lithium carbonate and diazepam treatment." Br Med J 2 (1977): 22
  9. Stovner J, Endresen R "Intravenous anaesthesia with diazepam." Acta Anaesthesiol Scand 24 (1965): 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 36 (1984): 244-7
  11. Feldman SA, Crawley BE "Interaction of diazepam with the muscle-relaxant drugs." Br Med J 1 (1970): 336-8
  12. Ochs HR, Greenblatt DJ, Verburg-Ochs B "Propranolol interactions with diazepam, lorazepam and alprazolam." Clin Pharmacol Ther 36 (1984): 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) 96 (1988): 63-6
  14. Tverskoy M, Fleyshman G, Ezry J, Bradley EL, Jr Kissin I "Midazolam-morphine sedative interaction in patients." Anesth Analg 68 (1989): 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 27 (1994): 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 80 Suppl (1989): 95-8
  18. Markowitz JS, Wells BG, Carson WH "Interactions between antipsychotic and antihypertensive drugs." Ann Pharmacother 29 (1995): 603-9
  19. "Product Information. Ultram (tramadol)." McNeil Pharmaceutical PROD (2001):
  20. "Product Information. Artane (trihexyphenidyl)." Lederle Laboratories PROD (2001):
  21. "Product Information. Ultiva (remifentanil)." Mylan Institutional (formally Bioniche Pharma USA Inc) PROD (2001):
  22. "Product Information. Seroquel (quetiapine)." Astra-Zeneca Pharmaceuticals PROD (2001):
  23. "Product Information. Meridia (sibutramine)." Knoll Pharmaceutical Company PROD (2001):
  24. "Product Information. Tasmar (tolcapone)." Valeant Pharmaceuticals PROD (2001):
  25. Miller LG "Herbal medicinals: selected clinical considerations focusing on known or potential drug-herb interactions." Arch Intern Med 158 (1998): 2200-11
  26. "Product Information. Precedex (dexmedetomidine)." Abbott Pharmaceutical PROD (2001):
  27. "Product Information. Trileptal (oxcarbazepine)." Novartis Pharmaceuticals PROD (2001):
  28. Ferslew KE, Hagardorn AN, McCormick WF "A fatal interaction of methocarbamol and ethanol in an accidental poisoning." J Forensic Sci 35 (1990): 477-82
  29. Plushner SL "Valerian: valeriana officinalis." Am J Health Syst Pharm 57 (2000): 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." O 0
  33. Cerner Multum, Inc. "Australian Product Information." O 0
  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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Moderate

chlorpheniramine stiripentol

Applies to: acetaminophen / chlorpheniramine / dextromethorphan and stiripentol

MONITOR: The concomitant administration of stiripentol may significantly increase plasma concentrations, pharmacologic effects, and toxicities of drugs that are substrates of CYP450 2C19, 3A4, and/or 2D6. The mechanism is inhibition of cytochrome P-450 metabolism by stiripentol.

MANAGEMENT: Clinical and laboratory monitoring for altered efficacy and safety is recommended during concomitant use. Dosage adjustments may be required if increased plasma levels or effects are observed.

References

  1. EMEA. European Medicines Agency "EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid" (2007):

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Moderate

dextromethorphan stiripentol

Applies to: acetaminophen / chlorpheniramine / dextromethorphan and stiripentol

MONITOR: Coadministration with CYP450 2D6 inhibitors may 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. Increased plasma concentrations increase the risk of dextromethorphan-related adverse effects (e.g., agitation, confusion, tremor, insomnia, diarrhea, and respiratory depression) and serotonin syndrome. Coadministration of dextromethorphan (60 mg orally, once) with the CYP450 2D6 inhibitor panobinostat (20 mg orally once a day on days 3, 5, and 8) in 14 patients with advanced cancer had a highly variable effect on dextromethorphan levels, increasing the peak plasma concentration (Cmax) of dextromethorphan by 20% to 200%, and total systemic exposure (AUC 0 to infinity) by 20% to 130%, compared to dextromethorphan given alone. In addition, multiple doses of the potent CYP450 2D6 inhibitor cinacalcet (50 mg daily), increased the AUC of a single 30 mg dextromethorphan dose by 11-fold in extensive metabolizers of this isoenzyme. The moderate CYP450 2D6 inhibitor asunaprevir, given at 200 mg twice daily, also increased Cmax and AUC of a single 30 mg dose of dextromethorphan by 2.7- and 3.9-fold, respectively, in 17 study subjects.

MANAGEMENT: Caution should be exercised if these drugs must be used together. Patients 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. Funck-Brentano C, Jacqz-Aigrain E, Leenhardt A, Roux A, Poirier JM, Jaillon P "Influence of amiodarone on genetically determined drug metabolism in humans." Clin Pharmacol Ther 50 (1991): 259-66
  2. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  3. Cerner Multum, Inc. "Australian Product Information." O 0
  4. "Product Information. Zytiga (abiraterone)." Centocor Inc (2011):
  5. "Product Information. Farydak (panobinostat)." Novartis Pharmaceuticals (2015):
  6. "Product Information. Qelbree (viloxazine)." Supernus Pharmaceuticals Inc (2021):
View all 6 references

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Drug and food interactions

Major

acetaminophen food

Applies to: acetaminophen / chlorpheniramine / dextromethorphan

GENERALLY AVOID: Chronic, excessive consumption of alcohol may increase the risk of acetaminophen-induced hepatotoxicity, which has included rare cases of fatal hepatitis and frank hepatic failure requiring liver transplantation. The proposed mechanism is induction of hepatic microsomal enzymes during chronic alcohol use, which may result in accelerated metabolism of acetaminophen and increased production of potentially hepatotoxic metabolites.

MANAGEMENT: In general, chronic alcoholics should avoid regular or excessive use of acetaminophen. Alternative analgesic/antipyretic therapy may be appropriate in patients who consume three or more alcoholic drinks per day. However, if acetaminophen is used, these patients should be cautioned not to exceed the recommended dosage (maximum 4 g/day in adults and children 12 years of age or older).

References

  1. Kaysen GA, Pond SM, Roper MH, Menke DJ, Marrama MA "Combined hepatic and renal injury in alcoholics during therapeutic use of acetaminophen." Arch Intern Med 145 (1985): 2019-23
  2. O'Dell JR, Zetterman RK, Burnett DA "Centrilobular hepatic fibrosis following acetaminophen-induced hepatic necrosis in an alcoholic." JAMA 255 (1986): 2636-7
  3. Seeff LB, Cuccherini BA, Zimmerman HJ, Adler E, Benjamin SB "Acetaminophen hepatotoxicity in alcoholics." Ann Intern Med 104 (1986): 399-404
  4. Thummel KE, Slattery JT, Nelson SD "Mechanism by which ethanol diminishes the hepatotoxicity of acetaminophen." J Pharmacol Exp Ther 245 (1988): 129-36
  5. McClain CJ, Kromhout JP, Peterson FJ, Holtzman JL "Potentiation of acetaminophen hepatotoxicity by alcohol." JAMA 244 (1980): 251-3
  6. Kartsonis A, Reddy KR, Schiff ER "Alcohol, acetaminophen, and hepatic necrosis." Ann Intern Med 105 (1986): 138-9
  7. Prescott LF, Critchley JA "Drug interactions affecting analgesic toxicity." Am J Med 75 (1983): 113-6
  8. "Product Information. Tylenol (acetaminophen)." McNeil Pharmaceutical PROD (2002):
  9. Whitcomb DC, Block GD "Association of acetaminopphen hepatotoxicity with fasting and ethanol use." JAMA 272 (1994): 1845-50
  10. Bonkovsky HL "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
  11. Nelson EB, Temple AR "Acetaminophen hepatotoxicity, fasting, and ethanol." JAMA 274 (1995): 301
  12. Zimmerman HJ, Maddrey WC "Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure." Hepatology 22 (1995): 767-73
View all 12 references

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Moderate

chlorpheniramine food

Applies to: acetaminophen / chlorpheniramine / dextromethorphan

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 15 (1986): 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

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Moderate

dextromethorphan food

Applies to: acetaminophen / chlorpheniramine / dextromethorphan

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 15 (1986): 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

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Moderate

stiripentol food

Applies to: stiripentol

GENERALLY AVOID: Taking stiripentol on an empty stomach may reduce its oral bioavailability. Stiripentol degrades rapidly when exposed to gastric acid in an empty stomach.

GENERALLY AVOID: Alcohol may potentiate the depressant effects of stiripentol on the central nervous system. Concomitant use may result in increased sedation and dizziness as well as impairment of psychomotor skills.

GENERALLY AVOID: It is not known whether stiripentol may reduce theophylline and caffeine metabolism, as data on the potential for inhibition of CYP450 1A2 are limited. Consumption of foods and nutritional products such as cola drinks (which contain significant quantities of caffeine) and chocolate (which contains caffeine and trace amounts of theophylline) may be unsafe during treatment with stiripentol, particularly in children.

MANAGEMENT: Stiripentol should be taken during a meal for optimal absorption; however, it should not be taken with milk, dairy products (e.g., yogurt, soft cream cheese), fruit juice, or carbonated beverages. Patients should be advised to avoid or limit consumption of alcohol and to avoid activities requiring mental alertness such as driving or operating hazardous machinery until they know how the medication affects them. Food and beverages that may contain caffeine or theophylline such as colas, chocolate, coffee, tea, or energy drinks should also be avoided during treatment with stiripentol.

References

  1. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  2. EMEA. European Medicines Agency "EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid" (2007):
  3. "Product Information. Diacomit (stiripentol)." Biocodex USA (2018):

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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.

Further information

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