With the joint administration of clarithromycin and drugs, primarily metabolized by isoenzymes CYP3A, there may be a mutual increase in their concentrations, which may enhance or prolong both the therapeutic and side effects.
Contraindicated joint treatment with astemizole, cisapride, pimozide, terfenadine, ergotamine and other ergot alkaloids; alprazolam, midazolam, triazolam.
With caution appoint with carbamazepine, cilostazolum, cyclosporine, disopyramide, lovastatin, methylprednisolone, omeprazole, indirect anticoagulants (incl.warfarin), quinidine, rifabutin, sildenafil, simvastatin, tacrolimus, vinblastine, as well as phenytoin, theophylline and valproic acid (metabolized through other cytochrome P450 isoenzymes). It is necessary to adjust the dose of medicines and control the concentration in the blood.
When combined with astemizole, cisapride, pimozide, terfenadine, it is possible to increase the concentration of the latter in the blood, increase the interval of QT, the occurrence of arrhythmias, including ventricular tachycardia, incl. type "pirouette" and ventricular fibrillation.
When combined with ergotamine and dihydroergotamine, acute poisoning with drugs of the ergotamine group (vascular spasm, limb and other tissue ischemia including CNS) is possible.
Efavirenz, nevirapine, rifampicin, rifabutin and rifapentin (inducers of cytochrome P450) reduce the concentration of clarithromycin in the plasma and weaken the therapeutic effect of the latter, and, at the same time, increase the concentration of 14-hydroxyclarithromycin.
With the simultaneous administration of fluconazole at a dose of 200 mg daily and clarithromycin at a dose of 1 g / day, an increase Css and AUC clarithromycin by 33% and 18%, respectively.Correction of the dose of clarithromycin is not required.
With the simultaneous use of ritonavir 600 mg / day and clarithromycin 1 g / day, a decrease in the metabolism of clarithromycin (an increase in CmOh by 31%, the minimum Css by 182% and AUC by 77%), complete suppression of the formation of 14-hydroxyclarithromycin.
In patients with chronic renal failure, dose adjustment is necessary: with creatinine clearance of 30-60 ml / min, the dose of clarithromycin should be reduced by 50%, with creatinine clearance less than 30 ml / min - by 75%. Ritonavir should not be taken with clarithromycin in a dose exceeding 1 g / day.
When combined with quinidine and disopyramide, there may be a ventricular tachycardia such as pirouette. ECG monitoring is required (interval increase Q-T), serum concentrations of these drugs.
Clarithromycin increases the concentrations of HMG-CoA reductase inhibitors (lovastatin and simvastatin) - the risk of rhabdomyolysis.
With the joint appointment of clarithromycin and omeprazole, an increase in CmOh, AUC and elimination half-life T1/2 omeprazole by 30%, 89%, and 34%, respectively. The average pH in the stomach for 24 hours was 5.2 with only omeprazole and 5.7 with omeprazole together with clarithromycin.
With the joint appointment of clarithromycin and indirect anticoagulants, it is possible to enhance the effect of the latter.
When co-prescribing clarithromycin with sildenafil, tadalafil or vardenafil (phosphodiesterase-5 inhibitors), it is possible to increase the inhibitory effect on phosphodiesterase. It may be necessary to reduce the dose of phosphodiesterase-5 inhibitors.
With the joint appointment of clarithromycin with theophylline and carbamazepine, an increase in the concentration of the latter in the systemic circulation is possible.
When co-prescribing clarithromycin with tolterodine in patients with slow metabolism via isoenzyme CYP2D6, a dose reduction of tolterodine in the presence of clarithromycin (an inhibitor of isoenzymes CYP3A).
With the simultaneous use of clarithromycin 1 g / day with midazolam (oral), an increase AUC midazolam 7 times. It is necessary to avoid the combined oral administration of clarithromycin and midazolam and other benzodiazepines, which are metabolized by isoenzymes CYP3A (triazolam and alprazolam). With the application of both midazolam (IV) and clarithromycin, a dose adjustment may be necessary.The same precautions should be applied to other benzodiazepines that are metabolized by isoenzymes CYP3A. For benzodiazepines, the excretion of which does not depend on isoenzymes CYP3A (temazepam, nitrazepam, lorazepam), clinically significant interaction with clarithromycin is unlikely.
When co-administered with clarithromycin and colchicine, colchicine may be enhanced. It is necessary to monitor the possible development of clinical symptoms of colchicine intoxication, especially in elderly patients and patients with chronic renal failure (reported fatal cases).
When co-administered with clarithromycin and digoxin, the concentration of digoxin in the serum should be carefully monitored (potentially developing potentially fatal arrhythmias).
Simultaneous reception of clarithromycin (tablets of usual release) and zidovudine by older HIV-infected patients can lead to a decrease Css zidovudine. It is necessary to select the doses of zidovudine and clarithromycin.
With the simultaneous administration of clarithromycin (1 g / day) and atazanavir (400 mg / day), an increase AUC atazanavir by 28%, clarithromycin by 2 times, decrease AUC 14-hydroxyclarithromycin by 70%.In patients with creatinine clearance of 30-60 ml / min, the dose of clarithromycin should be reduced by 50%. Clarithromycin in doses exceeding 1 g / day, can not be administered together with protease inhibitors.
With the joint administration of clarithromycin and itraconazole, a mutual increase in the concentration of drugs in the plasma is possible. For patients who simultaneously take itraconazole and clarithromycin, careful monitoring is necessary because of the possible enhancement or extension of the pharmacological effects of these drugs.
With concurrent administration of clarithromycin (1 g / day) and saquinavir (in soft gelatin capsules, 1200 mg 3 times a day), an increase AUC and Css saquinavir by 177% and 187%, respectively, and clarithromycin by 40%. When co-prescribing these two medicines for a limited time in the doses / dosage forms indicated above, dose adjustment is not required.
With a joint admission with verapamil possible lowering of blood pressure, bradyarrhythmia and lactic acidosis.