At simultaneous reception clarithromycin increases the concentration in the blood drugs metabolized in the liver with the help of cytochrome P450 isoenzymes (CYP3A), there may be a mutual increase in their concentrations, which may enhance or prolong both the therapeutic and side effects. Contraindicated joint reception with astemizole, cisapride, pimozide, terfenadine and other ergot alkaloids, alprazolam, midazolam, triazolam (for oral administration).
With caution apply with carbamazepine, cilostazol, cyclosporine, disopyramide, methylprednisolone, omeprazole, indirect anticoagulants (including warfarin), quinidine, rifabutin, sildenafil, tacrolimus, vinblastine, phenytoin, theophylline and valproic acid (metabolized through other isoenzymes of cytochrome P450). It is necessary to correct the dose of the drug and monitor the concentration in the blood.
When combined with cisapride, pimozide, terfenadine and astemisole possibly increasing the concentration of the latter in the blood, lengthening the interval QT, occurrence of arrhythmia, including ventricular tachycardia incl. type "pirouette", flutter and fibrillation of the ventricles.
When combined with ergotamine and dihydroergotamine possible acute poisoning with drugs of the group ergotamine (vascular spasm, ischemia of limbs and other tissues, including the central nervous system).
Efavirenz, nevirapine, rifampicin, rifabutin and rifapentin (inducers of cytochrome P450) reduce the concentration of clarithromycin in the plasma and weaken its therapeutic effect, and, at the same time, increase the concentration of 14 (R) -hydroxyclamirithromycin.
When sharing fluconazole in a dose of 200 mg daily and clarithromycin at a dose of 1 g / day, an increase in the equilibrium concentrationCss) in the blood and AUC clarithromycin by 33% and 18%, respectively. Correction of the dose of clarithromycin is not required.
When sharing ritonavir 600 mg / day and clarithromycin 1 g / day, a decrease in the metabolism of clarithromycin (an increase in Cmax by 31%, Css by 182% and AUC by 77%), total suppression of education 14 (R) -hydroxyclamirithromycin. In patients with CRF, dose adjustment is necessary: with a QC of 30-60 ml / min, the dose of clarithromycin should be reduced by 50%. Ritonavir should not be taken with clarithromycin in a dose exceeding 1 g / day.
With a joint reception with quinidine and disopyramide the occurrence of ventricular tachycardia such as "pirouette". ECG monitoring is required (interval increase QT), serum concentrations of these drugs.
Clarithromycin increases concentration inhibitors of HMG-Co-A-reductase (lovastatin, simvastatin) - risk of rhabdomyolysis.
When using clarithromycin and omeprazole it is possible to increase Cmax, AUC and 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.
When applied in conjunction with indirect anticoagulants it is possible to strengthen the effect of the latter.
When used with sildenafil, tadalafil or vardenafil (inhibitors of phosphodiesterase type 5 (PDE-5)), it is possible to increase the inhibitory effect on PDE. It may be necessary to reduce the dose of PDE-5 inhibitors.
With the combined use of clarithromycin with theophylline and carbamazepine it is possible to increase the concentration of the latter in the systemic circulation.
When used with tolterodine in patients with slow metabolism through CYP2D6, a dose reduction of tolterodine in the presence of clarithromycin (an inhibitor of isoenzymes CYP3A).
With the simultaneous administration of clarithromycin (1 g / day) with midazolam (orally) it is possible to 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). When using midazolam (intravenous) and clarithromycin, a dose adjustment may be required. The same precautions should be applied to other benzodiazepines, which 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.
With the combined use of clarithromycin and triazolam possible impact on the central nervous system (drowsiness, confusion).
When taking clarithromycin with colchicine it is possible to intensify the action of colchicine. It is necessary to monitor the possible development of clinical symptoms of colchicine intoxication, especially in elderly patients and patients with chronic renal failure (fatal cases have been reported).
With the joint administration of clarithromycin and digoxin Serum digoxin concentration should be carefully monitored (possibly increasing its concentration and developing potentially fatal arrhythmias).
Simultaneous reception of clarithromycin (tablets of usual liberation) and zidovudine in adults with HIV-infected patients may lead to a decrease Css zidovudine. It is necessary to select doses of clarithromycin and zidovudine. This type of interaction is not found in HIV-infected children receiving clarithromycin in the form of a suspension together with zidovudine.
With the simultaneous administration of clarithromycin (1 g / day) and atazanavir (400 mg / day) it is possible to increase AUC atazanavir by 28%, clarithromycin by 2 times, decrease AUC 14 (R) -hydroxyloxycarithromycin by 70%. In patients with KK 30-60 ml / min, the dose of clarithromycin should be reduced by 50%. Clarithromycin in doses exceeding 1 g / day, can not be used in conjunction with protease inhibitors.
With the simultaneous administration of clarithromycin (500 mg 2 times a day) together with etravirine a decrease in the concentration of clarithromycin in plasma by 53%; However, the concentration of its active metabolite (14 (R) -hydroxyclarithromycin) increased by 46%. 14(R) -hydroxyclamirithromycin has a reduced activity against Mycobacterium avium complex, therefore, a change in the total activity of clarithromycin and its metabolite in relation to this pathogen is possible.
With the joint administration of clarithromycin and itraconazole possibly a mutual increase in the concentration of drugs in the plasma. For patients who simultaneously take intraconazole 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 saquinade (in soft gelatin capsules, 1200 mg 3 times a day) may increase AUC and Css saquinavir by 117% and 187% respectively, and clarithromycin by 40%. When these two drugs are administered together for a limited time in the doses / dosage forms mentioned above, no dose adjustment is required.
With a joint reception with verapamil possibly lowering blood pressure, bradyarrhythmia and lactic acidosis.
With a joint reception with hypoglycemic agents, including insulin, the expressed hypoglycemia is possible.It is necessary to monitor the concentration of glucose in the blood.