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Drug Interactions between Limbitrol and Mylanta Ultimate Strength

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

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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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Minor

chlordiazePOXIDE aluminum hydroxide

Applies to: Limbitrol (amitriptyline / chlordiazepoxide) and Mylanta Ultimate Strength (aluminum hydroxide / magnesium hydroxide)

A number of studies have reported that antacids can delay the gastrointestinal absorption and reduce the peak plasma concentration (Cmax) of some benzodiazepines, including clorazepate, chlordiazepoxide and diazepam, although the overall extent of absorption is generally not affected. The exact mechanism of interaction is unknown, but may involve delayed gastric emptying or cation binding of the benzodiazepine. As a result, benzodiazepine onset of action may be delayed and clinical effects diminished. However, one study reported a significant increase in diazepam absorption during coadministration with aluminum hydroxide, and there was a marginal increase in the onset of sedative effect. Aluminum hydroxide also increased triazolam Cmax and systemic exposure (AUC) in 11 dialysis patients such that their drug levels reached into the range observed for the matched controls. In contrast, another study by the same group of investigators found no significant effect of aluminum hydroxide on temazepam absorption or Cmax in 11 patients with end-stage renal disease. A multi-dose study also failed to find an effect of antacids on the steady-state levels of N-desmethyldiazepam, the active metabolite of clorazepate, although an acidic environment is thought to be necessary for the rapid conversion. Based on available data, the clinical significance of this interaction appears to be minor. As a precaution, patients may consider separating the administration times of benzodiazepines and antacids or other oral medications that contain antacids (e.g., didanosine buffered tablets or pediatric oral solution) by 2 to 3 hours.

References

  1. Chun AH, Carrigan PJ, Hoffman DJ, Kershner RP, Stuart JD "Effect of antacids on absorption of clorazepate." Clin Pharmacol Ther 22 (1977): 329-35
  2. Nair SG, Gamble JA, Dundee JW, Howard PJ "The influence of three antacids on the absorption and clinical action of oral diazepam." Br J Anaesth 48 (1976): 1175-80
  3. Greenblatt DJ, Shader RI, Harmatz JS, Franke K, Koch-Weser J "Absorption rate, blood concentrations, and early response to oral chlordiazepoxide." Am J Psychiatry 134 (1977): 559-62
  4. Greenblatt DJ, Allen MD, MacLaughlin DS, Harmatz JS, Shader RI "Diazepam absorption: effect of antacids and food." Clin Pharmacol Ther 24 (1978): 600-9
  5. Shader RI, Georgotas A, Greenblatt DJ, Harmatz JS, Allen MD "Impaired absorption of desmethyldiazepam from clorazepate by magnesium aluminum hydroxide." Clin Pharmacol Ther 24 (1978): 308-15
  6. Kroboth PD, Smith RB, Rault R, Silver MR, Sorkin MI, Puschett JB, Juhl RP "Effects of end-stage renal disease and aluminum hydroxide on temazepam kinetics." Clin Pharmacol Ther 37 (1985): 453-9
  7. Kroboth PD, Smith RB, Silver MR, Rault R, Sorkin MI, Puschett JB, Juhl RP "Effects of end stage renal disease and aluminium hydroxide on triazolam pharmacokinetics." Br J Clin Pharmacol 19 (1985): 839-42
  8. Shader RI, Ciraulo DA, Greenblatt DJ, Harmatz JS "Steady-state plasma desmethyldiazepam during long-term clorazepate use: effects of antacids." Clin Pharmacol Ther 31 (1982): 180-3
  9. Greenblatt DJ, Shader RI, Harmatz JS, Franke K, Koch-Weser J "Influence of magnesium and aluminum hydroxide mixture on chlordiazepoxide absorption." Clin Pharmacol Ther 19 (1976): 234-9
View all 9 references

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Minor

chlordiazePOXIDE magnesium hydroxide

Applies to: Limbitrol (amitriptyline / chlordiazepoxide) and Mylanta Ultimate Strength (aluminum hydroxide / magnesium hydroxide)

A number of studies have reported that antacids can delay the gastrointestinal absorption and reduce the peak plasma concentration (Cmax) of some benzodiazepines, including clorazepate, chlordiazepoxide and diazepam, although the overall extent of absorption is generally not affected. The exact mechanism of interaction is unknown, but may involve delayed gastric emptying or cation binding of the benzodiazepine. As a result, benzodiazepine onset of action may be delayed and clinical effects diminished. However, one study reported a significant increase in diazepam absorption during coadministration with aluminum hydroxide, and there was a marginal increase in the onset of sedative effect. Aluminum hydroxide also increased triazolam Cmax and systemic exposure (AUC) in 11 dialysis patients such that their drug levels reached into the range observed for the matched controls. In contrast, another study by the same group of investigators found no significant effect of aluminum hydroxide on temazepam absorption or Cmax in 11 patients with end-stage renal disease. A multi-dose study also failed to find an effect of antacids on the steady-state levels of N-desmethyldiazepam, the active metabolite of clorazepate, although an acidic environment is thought to be necessary for the rapid conversion. Based on available data, the clinical significance of this interaction appears to be minor. As a precaution, patients may consider separating the administration times of benzodiazepines and antacids or other oral medications that contain antacids (e.g., didanosine buffered tablets or pediatric oral solution) by 2 to 3 hours.

References

  1. Chun AH, Carrigan PJ, Hoffman DJ, Kershner RP, Stuart JD "Effect of antacids on absorption of clorazepate." Clin Pharmacol Ther 22 (1977): 329-35
  2. Nair SG, Gamble JA, Dundee JW, Howard PJ "The influence of three antacids on the absorption and clinical action of oral diazepam." Br J Anaesth 48 (1976): 1175-80
  3. Greenblatt DJ, Shader RI, Harmatz JS, Franke K, Koch-Weser J "Absorption rate, blood concentrations, and early response to oral chlordiazepoxide." Am J Psychiatry 134 (1977): 559-62
  4. Greenblatt DJ, Allen MD, MacLaughlin DS, Harmatz JS, Shader RI "Diazepam absorption: effect of antacids and food." Clin Pharmacol Ther 24 (1978): 600-9
  5. Shader RI, Georgotas A, Greenblatt DJ, Harmatz JS, Allen MD "Impaired absorption of desmethyldiazepam from clorazepate by magnesium aluminum hydroxide." Clin Pharmacol Ther 24 (1978): 308-15
  6. Kroboth PD, Smith RB, Rault R, Silver MR, Sorkin MI, Puschett JB, Juhl RP "Effects of end-stage renal disease and aluminum hydroxide on temazepam kinetics." Clin Pharmacol Ther 37 (1985): 453-9
  7. Kroboth PD, Smith RB, Silver MR, Rault R, Sorkin MI, Puschett JB, Juhl RP "Effects of end stage renal disease and aluminium hydroxide on triazolam pharmacokinetics." Br J Clin Pharmacol 19 (1985): 839-42
  8. Shader RI, Ciraulo DA, Greenblatt DJ, Harmatz JS "Steady-state plasma desmethyldiazepam during long-term clorazepate use: effects of antacids." Clin Pharmacol Ther 31 (1982): 180-3
  9. Greenblatt DJ, Shader RI, Harmatz JS, Franke K, Koch-Weser J "Influence of magnesium and aluminum hydroxide mixture on chlordiazepoxide absorption." Clin Pharmacol Ther 19 (1976): 234-9
View all 9 references

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Drug and food interactions

Major

aluminum hydroxide food

Applies to: Mylanta Ultimate Strength (aluminum hydroxide / magnesium hydroxide)

GENERALLY AVOID: The concomitant administration of aluminum-containing products (e.g., antacids and phosphate binders) and citrates may significantly increase serum aluminum concentrations, resulting in toxicity. Citrates or citric acid are contained in numerous soft drinks, citrus fruits, juices, and effervescent and dispersible drug formulations. Citrates enhance the gastrointestinal absorption of aluminum by an unknown mechanism, which may involve the formation of a soluble aluminum-citrate complex. Various studies have reported that citrate increases aluminum absorption by 4.6- to 50-fold in healthy subjects. Patients with renal insufficiency are particularly at risk of developing hyperaluminemia and encephalopathy. Fatalities have been reported. Patients with renal failure or on hemodialysis may also be at risk from soft drinks and effervescent and dispersible drug formulations that contain citrates or citric acid. It is unknown what effect citrus fruits or juices would have on aluminum absorption in healthy patients.

MANAGEMENT: The concomitant use of aluminum- and citrate-containing products and foods should be avoided by renally impaired patients. Hemodialysis patients should especially be cautioned about effervescent and dispersible over-the-counter remedies and soft drinks. Some experts also recommend that healthy patients should separate doses of aluminum-containing antacids and citrates by 2 to 3 hours.

ADJUST DOSING INTERVAL: The administration of aluminum-containing antacids with enteral nutrition may result in precipitation, formation of bezoars, and obstruction of feeding tubes. The proposed mechanism is the formation of an insoluble complex between the aluminum and the protein in the enteral feeding. Several cases of esophageal plugs and nasogastric tube obstructions have been reported in patients receiving high-protein liquids and an aluminum hydroxide-magnesium hydroxide antacid or an aluminum hydroxide antacid.

MANAGEMENT: Some experts recommend that antacids should not be mixed with or given after high protein formulations, that the antacid dose should be separated from the feeding by as much as possible, and that the tube should be thoroughly flushed before administration.

References

  1. Cerner Multum, Inc. "UK Summary of Product Characteristics." O 0
  2. Wohlt PD, Zheng L, Gunderson S, Balzar SA, Johnson BD, Fish JT "Recommendations for the use of medications with continuous enteral nutrition." Am J Health Syst Pharm 66 (2009): 1438-67

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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.

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

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