Josamycin Theophylline

Troleandomycin can increase serum theophylline levels, causing toxicity if the dosage is not reduced. Azithromycin, clarithromycin, dirithromycin, josamycin, midecamycin, rokitamycin, spiramycin, and telithromycin normally only cause modest changes in theophylline levels or do not interact at all. There are unexplained and isolated case reports of theophylline toxicity with josamycin and clarithromycin. Roxithromycin usually has no relevant interaction but a significant increase in theophylline levels was seen in one study. See also Theophylline + Macrolides Erythromycin , p.ll87. 

No clinically significant changes in serum theophylline levels were seen in 5 studies in patients (both adults and children) " or healthy subjects given josamycin, but a modest rise in theophylline levels was described in one study in children. Another study reported a23% reduction in the levels of theophylline (given as intravenous aminophylline) in 5 patients with particularly severe respiratory impairment, but no significant effect in 5 other patients with less severe disease. However, an isolated report describes theophylline toxicity in a 80-year-old man who was given josamycin. 

It is believed that troleandomycin forms inactive cytochrome P450-metab-olite complexes within the liver, the effect of which is to reduce the metabolism (A/-demethylation and 8-hydroxylation) of theophylline, thereby reducing its clearance and increasing its levels. Clarithromycin, josamycin, midecamycin, and roxithromycin are thought to rarely form complexes, and azithromycin, dirithromycin, rokitamycin and spiramycin are not thought to inactivate cytochrome P450. ... 

The interaction between theophylline and troleandomycin is established and well documented. If troleandomycin is given, monitor the levels of theophylline closely and adjust the dose as necessary. Reductions of 25 to 50% may be needed. The situation with roxithromycin is uncertain since only 1 of 4 studies suggested an interaction, but it would be prudent to be alert for the need to reduce the theophylline dosage. Alternative mac-rolides that usually interact only moderately, or not at all are azithromycin, clarithromycin, dirithromycin, josamycin, midecamycin, rokitamycin and spiramycin. Telithromycin may also he a suitable alternative. However, even with these macrolides it would still be prudent to monitor the outcome because a few patients, especially those with theophylline levels at the high end of the range, may need some small theophylline dosage adjustments. In the case of azithromycin, care should be taken in adjusting the dose based on theophylline levels taken after about 5 days of concurrent use, as they may only he a reflection of a transient drop. In addition, acute infection perse may alter theophylline pharmacokineties. 

Brazier JL, Kofman J, Faucon G, Perrin-Fayolle M, Lepape A, Lanoue R Retard d ehmina-tion de la theophylline du a la troleandomycine. Absence d effet de la josamycine. Therc ie (1980) 35,545-9. 

Bartolucci L, Gradoli C, Vincenzi V, lapadre M Valori C. Microlide antibiotics and serum theophylline levels in relation to the severity of the req>iratc y impairment a comparison between the effects of erythromycin and josamycin. Chemioterapia (1984) 3,286-90. 

Barbare JC, Martin F, Biour M Surdosage en theophylline at ancmalies des tests hepatiques associes a la prise de josamycine. Thercq>ie (1990) 45, 357-58. 

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