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Drug Interactions between midazolam and troleandomycin

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

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Interactions between your drugs

Moderate

midazolam troleandomycin

Applies to: midazolam and troleandomycin

MONITOR: Macrolide antibiotics may increase and prolong the CNS effects of certain benzodiazepines. The mechanism is inhibition of CYP450 3A4 hepatic oxidation of the benzodiazepines. Midazolam, triazolam, and alprazolam have been specifically studied in this regard. Lorazepam, oxazepam, and temazepam are hepatically conjugated and are not expected to interact. Azithromycin and dirithromycin do not inhibit CYP450 isoenzymes.

MANAGEMENT: Patients receiving this combination should be monitored for excessive or prolonged sedation. Non-interacting benzodiazepines or antimicrobials may be considered as alternatives.

References

  1. Phillips JP, Antal EJ, Smith RB (1986) "A pharmacokinetic drug interaction between erythromycin and triazolam." J Clin Psychopharmacol, 6, p. 297-9
  2. Warot D, Bergougnan L, Lamiable D, et al. (1987) "Troleandomycin-triazolam interaction in healthy volunteers: pharmacokinetic and psychometric evaluation." Eur J Clin Pharmacol, 32, p. 389-93
  3. Mattila MJ, Idanpaanheikkila JJ, Tornwall M, Vanakoski J (1993) "Oral single doses of erythromycin and roxithromycin may increase the effects of midazolam on human performance." Pharmacol Toxicol, 73, p. 180-5
  4. Wrighton SA, Ring BJ (1994) "Inhibition of human CYP3A catalyzed 1'-hydroxy midazolam formation by ketoconazole, nifedipine, erythromycin, cimetidine, and nizatidine." Pharm Res, 11, p. 921-4
  5. Amsden GW (1995) "Macrolides versus azalides: a drug interaction update." Ann Pharmacother, 29, p. 906-17
  6. Luurila H, Olkkola KT, Neuvonen PJ (1996) "Interaction between erythromycin and the benzodiazepines diazepam and flunitrazepam." Pharmacol Toxicol, 78, p. 117-22
  7. Zimmermann T, Yeates RA, Laufen H, Scharpf F, Leitold M, Wildfeuer A (1996) "Influence of the antibiotics erythromycin and azithromycin on the pharmacokinetics and pharmacodynamics of midazolam." Arzneimittelforschung, 46, p. 213-7
  8. Yasui N, Otani K, Kaneko S, et al. (1996) "A kinetic and dynamic study of oral alprazolam with and without erythromycin in humans: in vivo evidence for the involvement of CYP3a4 in alprazolam metabolism." Clin Pharmacol Ther, 59, p. 514-9
  9. Yeates RA, Laufen H, Zimmermann T (1996) "Interaction between midazolam and clarithromycin: comparison with azithromycin." Int J Clin Pharmacol Ther, 34, p. 400-5
  10. Yeates RA, Laufen H, Zimmermann T, Schumacher T (1997) "Pharmacokinetic and pharmacodynamic interaction study between midazolam and the macrolide antibiotics, erythromycin clarithromycin, and the azalide azithromycin." Int J Clin Pharmacol Ther, 35, p. 577-9
  11. Gorski JC, Jones DR, HaehnerDaniels BD, Hamman MA, OMara EM, Hall SD (1998) "The contribution of intestinal and hepatic CYP3A to the interaction between midazolam and clarithromycin." Clin Pharmacol Ther, 64, p. 133-43
  12. Kanamitsu S, Ito K, Green CE, Tyson CA, Shimada N, Sugiyama Y (2000) "Prediction of in vivo interaction between triazolam and erythromycin based on in vitro studies using human liver microsomes and recombinant human CYP3A4." Pharmaceut Res, 17, p. 419-26
  13. Ito K, Ogihara K, Kanamitsu SI, Itoh T (2003) "Prediction of the in vivo interaction between midazolam and macrolides based on in vitro studies using human liver microsomes." Drug Metab Dispos, 31, p. 945-954
View all 13 references

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Drug and food interactions

Moderate

midazolam food

Applies to: midazolam

GENERALLY AVOID: The pharmacologic activity of oral midazolam, triazolam, and alprazolam may be increased if taken after drinking grapefruit juice. The proposed mechanism is CYP450 3A4 enzyme inhibition. In addition, acute alcohol ingestion may potentiate 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.

MANAGEMENT: The manufacturer recommends that grapefruit juice should not be taken with oral midazolam. Patients taking triazolam or alprazolam should be monitored for excessive sedation. Alternatively, the patient could consume orange juice which does not interact with these drugs. Patients should be advised to avoid alcohol during benzodiazepine therapy.

References

  1. (2002) "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn
  2. (2002) "Product Information. Valium (diazepam)." Roche Laboratories
  3. (2001) "Product Information. Halcion (triazolam)." Pharmacia and Upjohn
  4. (1995) "Grapefruit juice interactions with drugs." Med Lett Drugs Ther, 37, p. 73-4
  5. Kupferschmidt HHT, Ha HR, Ziegler WH, Meier PJ, Krahenbuhl S (1995) "Interaction between grapefruit juice and midazolam in humans." Clin Pharmacol Ther, 58, p. 20-8
  6. Hukkinen SK, Varhe A, Olkkola KT, Neuvonen PJ (1995) "Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice." Clin Pharmacol Ther, 58, p. 127-31
  7. Bailey DG, Dresser GR, Kreeft JH, Munoz C, Freeman DJ, Bend JR (2000) "Grapefruit-felodipine interaction: Effect of unprocessed fruit and probable active ingredients." Clin Pharmacol Ther, 68, p. 468-77
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.

Further information

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