Telithromycin drug interactions
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Sheng Shi, M.D. [2]
Drug Interactions
In vitro interactions
In vitro studies using a model compound have shown that telithromycin may act as an inhibitor for the hepatic uptake transporters OATP1B1 and OATP1B3. Although the clinical relevance of this finding is unknown, it is possible that concomitant administration of telithromycin with drugs that are substrates of OATP family members could result in increased plasma concentrations of the co-administered drug.
In vivo interactions
Studies were performed to evaluate the effect of CYP 3A4 inhibitors on telithromycin and the effect of telithromycin on drugs that are substrates of CYP 3A4 and CYP 2D6. In addition, drug interaction studies were conducted with several other concomitantly prescribed drugs.
CYP 3A4 inhibitors
Itraconazole
A multiple-dose interaction study with itraconazole showed that Cmax of telithromycin was increased by 22% and AUC by 54%.
Ketoconazole
A multiple-dose interaction study with ketoconazole showed that Cmax of telithromycin was increased by 51% and AUC by 95%.
Grapefruit juice=
When telithromycin was given with 240 mL of grapefruit juice after an overnight fast to healthy subjects, the pharmacokinetics of telithromycin were not affected.
CYP 3A4 substrates
Cisapride
Steady-state peak plasma concentrations of cisapride (an agent with the potential to increase QT interval) were increased by 95% when co-administered with repeated doses of telithromycin, resulting in significant increases in QTc. (See CONTRAINDICATIONS)
Simvastatin
When simvastatin was co-administered with telithromycin, there was a 5.3-fold increase in simvastatin Cmax, an 8.9-fold increase in simvastatin AUC, a 15-fold increase in the simvastatin active metabolite Cmax, and a 12-fold increase in the simvastatin active metabolite AUC. (See PRECAUTIONS)
In another study, when simvastatin and telithromycin were administered 12 hours apart, there was a 3.4-fold increase in simvastatin Cmax, a 4.0-fold increase in simvastatin AUC, a 3.2-fold increase in the active metabolite Cmax, and a 4.3-fold increase in the active metabolite AUC. (See PRECAUTIONS)
Midazolam
Concomitant administration of telithromycin with intravenous or oral midazolam resulted in 2- and 6-fold increases, respectively, in the AUC of midazolam due to inhibition of CYP 3A4-dependent metabolism of midazolam. (See PRECAUTIONS)
CYP 2D6 substrates
Paroxetine
There was no pharmacokinetic effect on paroxetine when telithromycin was co-administered.
Metoprolol
When metoprolol was co-administered with telithromycin, there was an increase of approximately 38% on the Cmax and AUC of metoprolol, however, there was no effect on the elimination half-life of metoprolol. Telithromycin exposure is not modified with concomitant single-dose administration of metoprolol. (See PRECAUTIONS, Drug interactions)
Other drug interactions
Digoxin
The plasma peak and trough levels of digoxin were increased by 73% and 21%, respectively, in healthy volunteers when co-administered with telithromycin. However, trough plasma concentrations of digoxin (when equilibrium between plasma and tissue concentrations has been achieved) ranged from 0.74 to 2.17 ng/mL. There were no significant changes in ECG parameters and no signs of digoxin toxicity. (See PRECAUTIONS)
=Theophylline
When theophylline was co-administered with repeated doses of telithromycin, there was an increase of approximately 16% and 17% on the steady-state Cmax and AUC of theophylline. Co-administration of theophylline may worsen gastrointestinal side effects such as nausea and vomiting, especially in female patients. It is recommended that telithromycin should be taken with theophylline 1 hour apart to decrease the likelihood of gastrointestinal side effects.
Sotalol
Telithromycin has been shown to decrease the Cmax and AUC of sotalol by 34% and 20%, respectively, due to decreased absorption.
Warfarin
When co-administered with telithromycin in healthy subjects, there were no pharmacodynamic or pharmacokinetic effects on racemic warfarin.
Oral contraceptives
When oral contraceptives containing ethinyl estradiol and levonorgestrel were co-administered with telithromycin, the steady-state AUC of ethinyl estradiol did not change and the steady-state AUC of levonorgestrel was increased by 50%. The pharmacokinetic/pharmacodynamic study showed that telithromycin did not interfere with the antiovulatory effect of oral contraceptives containing ethinyl estradiol and levonorgestrel.
Ranitidine, antacid
There was no clinically relevant pharmacokinetic interaction of ranitidine or antacids containing aluminum and magnesium hydroxide on telithromycin.
Rifampin
During concomitant administration of rifampin and KETEK in repeated doses, Cmax and AUC of telithromycin were decreased by 79%, and 86%, respectively. (See PRECAUTIONS, Drug Interactions)[1]
References
- ↑ "KETEK (TELITHROMYCIN) TABLET, FILM COATED [PHYSICIANS TOTAL CARE, INC.]". Retrieved 9 January 2014.
Adapted from the FDA Package Insert.