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Drug Interactions between Halfan and Limbitrol

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

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Interactions between your drugs

Major

amitriptyline halofantrine

Applies to: Limbitrol (amitriptyline / chlordiazepoxide) and Halfan (halofantrine)

CONTRAINDICATED: Halofantrine can cause dose-related prolongation of the QT interval at recommended therapeutic doses. QTc interval prolongation and death have been reported during combination use of halofantrine and mefloquine. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death.

MANAGEMENT: Coadministration of halofantrine with other drugs that can prolong the QT interval is considered contraindicated. The manufacturer recommends performing an ECG before initiating halofantrine therapy and monitoring cardiac rhythm during and for 8 to 12 hours after completion of therapy.

References

  1. "Product Information. Mefloquine Hydrochloride (mefloquine)." Hikma USA (formerly West-Ward Pharmaceutical Corporation) (2021):
  2. Giao PT, de Vries PJ "Pharmacokinetic interactions of antimalarial agents." Clin Pharmacokinet 40 (2001): 343-73
  3. "Product Information. Halfan (halofantrine)." GlaxoSmithKline (2003):
  4. Nosten F, ter Kuile FO, Luxemburger C, et al. "Cardiac effects of antimalarial treatment with halofantrine." Lancet 341 (1993): 1054-6
  5. "Sudden death in a traveler following halofantrine administration--Togo, 2000." MMWR Morb Mortal Wkly Rep 50 (2001): 169-70, 179
  6. Abernethy DR, Wesche DL, Barbey JT, et al. "Stereoselective halofantrine disposition and effect: concentration-related QTc prolongation." Br J Clin Pharmacol 51 (2001): 231-7
  7. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  8. Canadian Pharmacists Association "e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink" (2006):
  9. Cerner Multum, Inc. "Australian Product Information." O 0
View all 9 references

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Moderate

amitriptyline chlordiazePOXIDE

Applies to: Limbitrol (amitriptyline / chlordiazepoxide) and Limbitrol (amitriptyline / chlordiazepoxide)

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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Drug and food interactions

Major

halofantrine food

Applies to: Halfan (halofantrine)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentration of halofantrine. The mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. After administration of 500 mg with 250 mL regular-strength grapefruit juice daily for 3 days, average halofantrine AUC increased 2.8-fold and peak plasma concentrations increased 3.2-fold, compared to water, in healthy subjects (n=12). QT interval prolongation increased from an average of 17 ms with water to 31 ms with grapefruit juice. Halofantrine, even at recommended doses, can cause dose-related prolongation of the QT interval, resulting in an elevated risk of potentially fatal ventricular arrhythmias including ventricular tachycardia and torsade de pointes.

ADJUST DOSING INTERVAL: The presence of food may increase the absorption and toxicity of halofantrine. Peak plasma concentrations increased seven-fold and AUC increased three-fold in healthy subjects when halofantrine was administered with high-fat food.

MANAGEMENT: The authors of the study recommend that grapefruit juice be avoided during halofantrine therapy. The manufacturer recommends performing an ECG before initiating halofantrine therapy and cardiac monitoring during and for 8 to 12 hours after completion of therapy. Halofantrine should be taken on an empty stomach at least 1 hour before or 2 hours after food.

References

  1. Giao PT, de Vries PJ "Pharmacokinetic interactions of antimalarial agents." Clin Pharmacokinet 40 (2001): 343-73
  2. "Product Information. Halfan (halofantrine)." GlaxoSmithKline (2003):
  3. Charbit B, Becquemont L, Lepere B, Peytavin G, Funck-Bretano C "Pharmacokinetic and pharmacodynamic interaction between grapefruit juice and halofantrine." Clin Pharmacol Ther 72 (2002): 514-23
  4. Abernethy DR, Wesche DL, Barbey JT, et al. "Stereoselective halofantrine disposition and effect: concentration-related QTc prolongation." Br J Clin Pharmacol 51 (2001): 231-7
View all 4 references

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Moderate

chlordiazePOXIDE food

Applies to: Limbitrol (amitriptyline / chlordiazepoxide)

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

amitriptyline food

Applies to: Limbitrol (amitriptyline / chlordiazepoxide)

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 25 (1983): 325-31
  2. Warrington SJ, Ankier SI, Turner P "Evaluation of possible interactions between ethanol and trazodone or amitriptyline." Neuropsychobiology 15 (1986): 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 24 (1983): 615-21
  4. Ciraulo DA, Barnhill JG, Jaffe JH "Clinical pharmacokinetics of imipramine and desipramine in alcoholics and normal volunteers." Clin Pharmacol Ther 43 (1988): 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 17 (1975): 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 51 (1990): 366-72
  7. Ciraulo DA, Alderson LM, Chapron DJ, Jaffe JH, Subbarao B, Kramer PA "Imipramine disposition in alcoholics." J Clin Psychopharmacol 2 (1982): 2-7
View all 7 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.

See also

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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.

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