Azithromycin + Midazolam = Unknown or no reaction

Effect on Concentration

Azithromycin
Unknown
Applies within class?
No
Midazolam
Unknown
Applies within class?
No

Pharmacologic Effects

Azithromycin
Effect
N/A
Applies within class?
No
Midazolam
Effect
N/A
Applies within class?
No

Interaction History

Precautionary, 22-May-2020;

Last Updated 22-May-2020

Summary

Onset of action of midazolam may be delayed by azithromycin, while no effect was observed in other studies.

Sources

Azithromycin Does Not Increase Plasma Concentrations of Oral Midazolam ^

Study Design

Interaction between azithromycin and midazolam was investigated in a double-blind, randomized crossover study of 2 phases. Ten healthy volunteers were given azithromycin (500 mg on day 1 and 250 mg on days 2-5) or placebo pretreatments. On day 5 they ingested 15 mg midazolam. Plasma samples were collected and psychomotor performance measured for 17 h.

Study Results

Azithromycin treatment increased the median (range) concentration peak time of midazolam from 1.0 (0.5-2) h to 1.25 (0.5-5) h and decreased plasma concentrations of midazolam during initial 3 hours after the intake of midazolam (p 0.05). Mean /- SE mean peak concentration of midazolam was decreased from 86 /- 17 ng ml-1 to 57 /- 9 ng ml-1 (p 0.05). Azithromycin did neither increase the total area under concentration-time curve nor change the elimination half-life of midazolam. In Maddox wing test the maximum effects of midazolam were reached later during azithromycin phase, but no other changes were observed in pharmacodynamics of midazolam.

Study Conclusions

Azithromycin may delay the absorption of midazolam, which can postpone the onset of action of midazolam.

References

Backman JT. Azithromycin does not increase plasma concentrations of oral midazolam. Int J Clin Pharmacol Ther. 1995; 6: 356-9.

Interaction Between Midazolam and Clarithromycin: Comparison With Azithromycin ^

Study Design

A comparative pharmacokinetic and pharmacodynamic investigation was carried out on the interaction between the hypnotic midazolam and 2 different macrolide-type antibiotics, clarithromycin and azithromycin. In an open randomized crossover study of 3 phases 12 healthy volunteers received either clarithromycin (250 mg twice a day for 5 days), azithromycin (500 mg once a day for 3 days) or no pretreatment. On the last day of antibiotic treatment they ingested 15 mg midazolam. Plasma samples were collected for midazolam analysis up to 24 h and pharmacodynamic performance measured by a series of tests up to 12 h.

Study Results

Pretreatment with clarithromycin caused large and statistically significant changes in both the pharmacokinetic and pharmacodynamic parameters of midazolam compared to control. For example, the AUC was increased from 248.84-888.75 hng/ml (factor of 3.57, p 0.0001) and the mean duration of sleep increased from 135.4 min to 281.3 min (p 0.05). No statistically significant effect was found with azithromycin in any test.

Study Conclusions

It is concluded that a drug interaction exists between midazolam and clarithromycin which could be of clinical importance. No such effect is present with azithromycin.

References

Yeates RA. Interaction between midazolam and clarithromycin: comparison with azithromycin. Int J Clin Pharmacol Ther. 1996; 9: 400-5.

Azithromycin Does Not Increase Plasma Concentrations of Oral Midazolam ^

Study Design

Interaction between azithromycin and midazolam was investigated in a double-blind, randomized crossover study of 2 phases. Ten healthy volunteers were given azithromycin (500 mg on day 1 and 250 mg on days 2-5) or placebo pretreatments. On day 5 they ingested 15 mg midazolam. Plasma samples were collected and psychomotor performance measured for 17 h.

Study Results

Azithromycin treatment increased the median (range) concentration peak time of midazolam from 1.0 (0.5-2) h to 1.25 (0.5-5) h and decreased plasma concentrations of midazolam during initial 3 hours after the intake of midazolam (p 0.05). Mean /- SE mean peak concentration of midazolam was decreased from 86 /- 17 ng ml-1 to 57 /- 9 ng ml-1 (p 0.05). Azithromycin did neither increase the total area under concentration-time curve nor change the elimination half-life of midazolam. In Maddox wing test the maximum effects of midazolam were reached later during azithromycin phase, but no other changes were observed in pharmacodynamics of midazolam.

Study Conclusions

Azithromycin may delay the absorption of midazolam, which can postpone the onset of action of midazolam.

References

Yeates RA. Interaction between midazolam and clarithromycin: comparison with azithromycin. Int J Clin Pharmacol Ther. 1996; 9: 400-5.