Troleandomycin, drug interactions

Grimsley, A., Gallagher, R., Hutchison, M., Pickup, K., Wilson, I. D., and Samuelsson, K. (2013). Drug-drug interactions and metabolism in cytochrome P450 2C knockout mice application to troleandomycin and midazolam. Biochem Pharmacol 86, 529-538. 

With the important exception of additive effects when combined with other CNS depressants, including alcohol, BZDs interact with very few drugs. Disulfiram (see the section The Alcoholic Patient in Chapter 14) and cimetidine may increase BZD blood levels, and diazepam may increase blood levels of digoxin and phenytoin. Antacids may reduce the clinical effects of clorazepate by hindering its biotransformation to desmethyidiazepam. Coadministration of a BZD and another drug known to induce seizures may possibly increase seizure risk, especially if the BZD is abruptly withdrawn. Furthermore, as noted earlier, important interactions have been reported among nefazodone, erythromycin, troleandomycin, and other macrolide antibiotics, as well as itraconazole. In each case, metabolism is inhibited, and triazolam levels can increase significantly. 

The differences in interactions of different macrohdes with cytochrome P450 are marked. Troleandomycin is a more potent inhibitor of microsomal drug metabolism than erythromycin, while josamycin, midecamycin, and spiramycin have not so far been incriminated (133,134). Azithromycin does not induce or inhibit cytochrome P450 in rats (135). 

Information is limited but an interaction between eletriptan and erythromycin appears to be established. Because of the elevated levels seen, the manufacturers advise against their concurrent use. Other drugs that are potent CYP3A4 inhibitors are predicted to raise serum eletriptan levels similarly. Such drugs include clarithromycin josamycin, and troleandomycin. In addition, the US manufacturers recommend that eletriptan should not be given within 72 hours of clarithromycin or troleandomycin. ... 

Ketoconazole can lead to reduced clearance of CS and a mild increase in levels (62,66,67). In addition, patients with significant liver or renal failure, age older than 65 years (68), or women receiving exogenous estrogen have increased unbound concentrations of prednisolone (69). Conversely, hyperthyroid patients have lower levels (70). There is one case report of an increased prothrombin time occurring in a patient on a stable dose of coumadin who subsequently received prednisone (71). This interaction seems rare and may be overshadowed by other drugs and events in the patient. Troleandomycin, a macrolide, has been shown to reduce clearance of methylprednisolone, but not prednisone (72). 

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