PubMed · 7829421
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J Durodie, B Slocombe. 1994. A clarithromycin sensitivity survey.. https://doi.org/10.1093/jac%2F34.3.446
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The newer macrolides and rifamycins (rifabutin) are major advances for treatment or prophylaxis of disease due to Mycobacterium avium complex. Although rifampin and rifabutin are known to induce the hepatic cytochrome P-450 system, their impact on the metabolism of clarithromycin is unknown. Clarithromycin and its major metabolite, 14-OH clarithromycin, were measured in the sera of patients receiving 500 mg twice a day before and after the addition of antituberculous drugs, including 600 mg/day of rifampin or rifabutin. Mean serum levels of clarithromycin given as a single agent were 5.4 +/- 2.1 micrograms/mL. These decreased to 0.7 +/- 0.6 micrograms/mL in patients receiving rifampin and 2.0 +/- 1.5 micrograms/mL in those receiving rifabutin. Mean serum levels of 14-OH clarithromycin were similar in the 3 groups (1.8-1.9 micrograms/mL). Rifampin and (to a lesser degree) rifabutin appear to induce the metabolism of clarithromycin.
BACKGROUND: Clarithromycin is a macrolide antibiotic very similar to erythromycin in structure and spectrum of activity. It has gained increasing use since its release in Canada in May 1992, partly because it is promoted as having less potential for drug interactions and adverse effects. However, as with all new medications, a high degree of vigilance for unreported adverse effects is advisable. CASE SUMMARY: A healthy 53-year-old lawyer was receiving long-term fluoxetine 80 mg hs and nitrazepam 10 mg hs for depression and mild sleep apnea. Subsequent to initiation of treatment with clarithromycin for a respiratory infection, he rapidly developed delirium, which cleared quickly after stopping all 3 medications. The delirium and psychosis did not recur when the infection was treated with erythromycin alone or after restarting fluoxetine and nitrazepam therapy at previous dosages in the absence of antibiotics. DISCUSSION: This man's delirium is consistent with fluoxetine intoxication, which appears to have resulted from inhibition of hepatic cytochrome P450 metabolism by clarithromycin. Undiagnosed, this serious drug reaction could have lead to serious medical and social consequences. CONCLUSIONS: As the use of clarithromycin increases, the potential for interactions with other drugs metabolized by the P450 enzyme system may be realized. Clinicians should consider which other medications a patient is receiving before prescribing clarithromycin or any macrolide antibiotic with potential to influence the P450 system.