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The equilibrium concentrations of the active metabolite 14-OH-clarithromycin has not significantly changed while the use of fluconazole. Changing the dosage of clarithromycin is required.
ritonavir
Use of clarithromycin and ritonavir resulted in a significant inhibition of metabolism of clarithromycin. Clarithromycin C max increased by 31%, C min - 182% and AUC - 77%. There was a complete suppression of the formation of 14-OH clarithromycin. Because of the large therapeutic window dose reduction of clarithromycin in patients with normal renal function is not required. However, in patients with renal failure requires correction dose: in patients with CL CR 30 - 60 ml / min dose of clarithromycin is necessary to reduce by 50%. In patients with severe renal impairment (CL CR
<30 ml / min) necessary to reduce the dose of clarithromycin by 75%. Doses of clarithromycin greater than 1g / day should not be used together with ritonavir.
Effect of clarithromycin on the pharmacokinetics of other drugs.
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There are post-marketing reports of twisting the development of ventricular tachycardia occurred during concomitant use of clarithromycin with quinidine or disopyramide. It is recommended that ECG monitoring for early detection of QT interval prolongation. During therapy with clarithromycin should monitor the concentrations of these drugs in the blood serum.
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The combined use of clarithromycin known inhibitor of CYP3A enzyme preparation and mainly metabolized CYP3A, may increase the concentration of the latter in the blood plasma, which in turn may enhance or prolong its therapeutic effect and the risk of adverse reactions.