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Drug Interactions between alprazolam and clarithromycin

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

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Interactions between your drugs

Major

clarithromycin ALPRAZolam

Applies to: clarithromycin and alprazolam

CONTRAINDICATED: Coadministration with potent CYP450 3A4 inhibitors such as the macrolide antibiotics clarithromycin, telithromycin and troleandomycin may increase and prolong the CNS-depressant effects of alprazolam. The mechanism is inhibition of CYP450 3A4 hepatic oxidation of the benzodiazepine. 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: Some authorities consider the concomitant use of alprazolam in combination with clarithromycin, telithromycin or troleandomycin to be contraindicated. 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. (2002) "Product Information. Xanax (alprazolam)." Pharmacia and Upjohn
  4. 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
  5. 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
  6. Amsden GW (1995) "Macrolides versus azalides: a drug interaction update." Ann Pharmacother, 29, p. 906-17
  7. Luurila H, Olkkola KT, Neuvonen PJ (1996) "Interaction between erythromycin and the benzodiazepines diazepam and flunitrazepam." Pharmacol Toxicol, 78, p. 117-22
  8. 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
  9. 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
  10. Yeates RA, Laufen H, Zimmermann T (1996) "Interaction between midazolam and clarithromycin: comparison with azithromycin." Int J Clin Pharmacol Ther, 34, p. 400-5
  11. 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
  12. 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
  13. 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
  14. 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
  15. Cerner Multum, Inc. "UK Summary of Product Characteristics."
  16. Cerner Multum, Inc. "Australian Product Information."
View all 16 references

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Drug and food interactions

Moderate

ALPRAZolam food

Applies to: alprazolam

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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Minor

clarithromycin food

Applies to: clarithromycin

Grapefruit juice may delay the gastrointestinal absorption of clarithromycin but does not appear to affect the overall extent of absorption or inhibit the metabolism of clarithromycin. The mechanism of interaction is unknown but may be related to competition for intestinal CYP450 3A4 and/or absorptive sites. In an open-label, randomized, crossover study consisting of 12 healthy subjects, coadministration with grapefruit juice increased the time to reach peak plasma concentration (Tmax) of both clarithromycin and 14-hydroxyclarithromycin (the active metabolite) by 80% and 104%, respectively, compared to water. Other pharmacokinetic parameters were not significantly altered. This interaction is unlikely to be of clinical significance.

References

  1. Cheng KL, Nafziger AN, Peloquin CA, Amsden GW (1998) "Effect of grapefruit juice on clarithromycin pharmacokinetics." Antimicrob Agents Chemother, 42, p. 927-9

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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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