Nitrazepam Erythromycin

A 53-year-old Canadian lawyer taking long-term fluoxetine and nitrazepam developed a frank psychosis 1-3 days after starting to take clarithromycin 500 mg/day for a chest infection (175). His symptoms resolved on withdrawal of all three drugs, and did not recur with erythromycin or when fluoxetine and nitrazepam were restarted in the absence of antibiotics. 

When 10 healthy subjects were given erythromycin 500 mg three times daily for 4 days, the AUC of a single 5-mg dose of nitrazepam was increased by 25%, the peak plasma levels were increased by 30% and the concentration peak time was reduced by over 50%. However, hardly any changes were seen in the psychomotor tests undertaken. ... 

Erythromycin. A study in 16 healthy subjects found that erythromycin 333 mg three times daily for 3 days, reduced the clearance of a single 500-microgram dose of triazolam by about 50%, doubled the AUC, and increased the maximum plasma levels by about one-third (from 2.8 to 4.1 nanograms/mL). Other reports confirm the marked decrease in clearance and an increase in peak levels. Repeated visual hallucinations and abnormal body sensations occurred in one patient with acute pneumonia and chronic renal failure taking erythromycin 600 mg daily after each dose of triazolam and nitrazepam. These symptoms had not occurred before the addition of erythromycin. ... 

Azithromycin does not interact with midazolam or triazolam, and the effects of roxithromycin on midazolam and triazolam, and of erythromycin on diazepam, flunitrazepam, nitrazepam, temazepam and zopiclone or clarithromycin on zolpidem appear to be small and unimportant, or the effects negligible, so that no special precautions seem to be necessary. 

Luurila H, OUckola KT, Neuvonen PI Interaction between erythromycin and nitrazepam in healthy volunteers. Pharmacol Toxicol (1995) 16, 255-8. 

A 53-year-old-man taking fluoxetine 80 mg and nitrazepam 10 mg at bedtime for depression and insomnia, was given clarithromycin 250 mg twice daily for a respiratory infection. Within a day he started to become increasingly contused and after 3 days was admitted to hospital with a diagnosis of psychosis and delirium. When no organic cause for the delirium could be found, all his medications were stopped, and erythromycin was started. His mental state returned to normal after 36 hours. Once the antibacterial course had finished, the fluoxetine and nitrazepam were restarted and no further problems occurred. ... 

---