Telithromycin Theophylline

Drugs that may be affected by telithromycin include cisapride, digoxin, ergot alkaloids, metoprolol, midazolam, pimozide, HMG-CoA reductase inhibitors, sotalol, and theophylline. 

The macrolide antibacterials (including erythromycin, clarithromycin and telithromycin) are often implicated in interactions, most frequently as a result of inhibition of the CYP3A4 enzyme system in the liver and enterocytes. Erythromycin inhibits the metabolism of carbamazepine, ciclosporin and theophylline significant increases in serum levels and features of toxicity have been documented. Careful clinical and pharmacokinetic monitoring are required in a patient taking any of these drugs who requires concomitant erythromycin. 

THEOPHYLLINE ISONIAZID, MACROLIDES (azithromycin, clarithromycin, erythromycin, telithromycin), QUINOLONES 1. t theophylline levels 2. Possibly 1 erythromycin levels when given orally 1. Inhibition of CYP2D6-mediated metabolism of theophylline (macrolides and quinolones -isoniazid not known) 2.1 bioavailability uncertain mechanism 1. Monitor theophylline levels before, during and after co-administration 2. Consider alternative macrolide... 

Fluconazole inhibits CYP3A4 and CYP2C9 and thus significantly increases plasma concentrations of amprenavir, cisapride, cyclosporine, phenytoin, sulfonylureas, tacrolimus, theophylline, telithromycin, and warfarin. Patients receiving >400 mg daily or azotemic patients may experience additional drug interactions. Rifampin decreases the fluconazole AUC by -25%. 

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. 

A study in 24 healthy subjeets given theophylline found that telithromycin 800 mg daily for 4 days did not have a clinically relevant effect on theophylline exposure. ... 

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. 

Bhargava V, Leroy B, Shi J, Montay G. Effect of telithromycin on the pharmacokinetics of theophylline in healthy volunteers. Intersci Conf Antimicrob Agents Chemother (2002) 42, 28. 

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