Clarithromycin use in patients who are receiving theophylline may be associated with an increase of serum theophylline concentrations. Monitoring of serum theophylline concentrations should be considered for patients receiving high doses of theophylline or with baseline concentrations in the upper therapeutic range. In two studies in which theophylline was administered with clarithromycin (a theophylline sustained-release formulation was dosed at either 6.5 mg/kg or 12 mg/kg together with 250 or 500 mg every 12h clarithromycin), the steady-state levels of Cmax, Cmin, and the area under the serum concentration time curve (AUC) of theophylline increased about 20%.
Concominant administration of single doses of clarithromycin and carbamazepine has been shown to result in increased plasma concentration of carbamazepine. Blood level monitoring of carbamazepine may be considered.
When clarithromycin and terfenadine were co-administered, plasma concentrations of the active metabolite of terfenadine were threefold higher, on average, than the values observed when terfenadine was administered alone. The pharmacokinetics of clarithromycin and the 14-hydroxy-clarithromycin were not significantly affected by the co-administration of terfenadine once clarithromycin reached steady state conditions. Concominant administration of clarithromycin with terfenadine is contraindicated. (See Contraindications).
Clarithromycin 500 mg every 8 hours was given in combination with omeprazole 40 mg daily to healthy adult subjects. The steady state plasma concentrations of omeprazole was increased (Cmax, AUC0-24 and T1/2 increases of 30%, 89% and 34%, respectively), by the concominant administration of clarithromycin. The mean 24 hour gastric pH value was 5.2 when omeprazole was administered alone and 5.7 when co-administered with clarithromycin.
Co-administration of clarithromycin with ranitidine, bismuth citrate resulted in increased plasma ranitidine concentrations (57%), increased plasma bismuth trough concentrations (48%) and increased 14-hydroxy-clarithromycin plasma concentrations (31%). These effects are clinically significant.
Simultaneous oral administration of clarithromycin and zidovudine to HIV infected adult patients resulted in decreased steady state zidovudine. When 500 mg of clarithromycin were administered twice daily, steady state zidovudine AUC was reduced by a mean of 12% (n=4). Individuals values ranged from a decrease of 34% to an increase of 14%. Based on limited data in 24 patients, when clarithromycin was administered 2 to 4 hours prior to oral zidovudine, the steady-state zidovudine Cmax was increased by approximately 2-folds, whereas the AUC was unaffected.
Simultaneous administration of clarithromycin and didanosine to 12 HIV infected adult patients resulted in no statistically significant change in didanosine pharmacokinetics.
Concominant administration of fluconazole 200 mg daily and clarithromycin 500 mg twice a daily to 21 healthy volunteers led to increases in the mean steady state clarithromycin Cmin and AUC of 33% and 18%, respectively. Steady-state concentrations of 14-OH clarithromycin were not significantly affected by concominant administration of fluconazole.