Seydon-Sanovel (Seidon-Sanovel)

When taking clarithromycin simultaneously with drugs, primarily metabolized isoenzymes CYP3A, there may be a mutual increase in their concentrations, which can enhance and prolong therapeutic and side effects. Contraindicated joint administration with astemizole, cisapride, pimozide, terfenadine, ergotamine and other ergot alkaloids, alprazolam, midazolam, triazolam.

Caution is taken with carbamazepine, cilostazol, cyclosporine, disopyramide, lovastatin, methylprednisolone, omeprazole, indirect anticoagulants (including warfarin), quinidine, rifabutin, sildenafil, simvastatin, tacrolimus, vinblastine, as well as phenytoin, theophylline and valproic acid (metabolized through other isoenzymes of cytochrome P450).At the same time, it is necessary to correct the dose of drugs and monitor their concentration in the blood.

When co-administered with terfenadine, cisapride, pimozide and astemizole, it is possible to increase the concentration of the latter in the blood and increase the interval QT, the occurrence of arrhythmia, including ventricular tachycardia, including "pirouette" type, and ventricular fibrillation.

With the combined use of clarithromycin with ergotamine and dihydroergotamine, acute poisoning with drugs of the ergotamine group, manifested by vasospasm, ischemia of limbs and other tissues, including the CNS, is possible.

Efavirenz, nevirapine, rifampicin, rifabutin and rifapentin, being inducers of the cytochrome P450 system, reduce the concentration of clarithromycin in the plasma and weaken its therapeutic effect and, at the same time, increase the concentration of 14-hydroxyclarithromycin.

With the simultaneous administration of clarithromycin (1 g / day) and fluconazole (200 mg daily), an increase Css and AUC clarithromycin by 33% and 18%, respectively, while correction of the dose of clarithromycin is not required.

With the simultaneous use of clarithromycin (1 g / day) and ritonavir (600 mg / day), a decrease in the metabolism of clarithromycin (an increase in C_mOh by 31%, the minimum Css by 182% and AUC by 77%), complete suppression of the formation of metabolite 14-hydroxyclarithromycin. Correction of the dose of clarithromycin in these cases is not required for patients with normal renal function. However, in patients with creatinine clearance from 30 to 60 ml / min, the dose of clarithromycin should be reduced by 50%. When creatinine clearance is less than 30 ml / min, the dose of clarithromycin should be reduced by 75%. With simultaneous treatment with ritonavir should not be prescribed 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 QT) and serum concentrations of these drugs.

Clarithromycin increases the concentrations of HMG-CoA reductase inhibitors (lovastatin and simvastatin) - possibly rhabdomyolysis.

With the simultaneous use of clarithromycin and omeprazole, an increase in C_mOh, AUC and T_1/2 omeprazole by 30%, 89% and 34%, respectively. The average pH value in the stomach for 24 hours with the simultaneous intake of omeprazole and clarithromycin was 5.7, and when taking omeprazole alone, it was 5.2.

With the combined use of clarithromycin with sildenafil, tadalafil or vardenafil, which are inhibitors of phosphodiesterase-5, it is possible to increase the inhibitory effect on phosphodiesterase, and a dose reduction of phosphodiesterase-5 inhibitors may be required.

With the simultaneous use of clarithromycin with theophylline and carbamazepine, there is an increase in the concentration in the systemic circulation of the latter.

With simultaneous use of clarithromycin with tolterodine in patients with slow metabolism through isoenzyme 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 (oral), an increase AUC the last in 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 simultaneous use of midazolam (IV) 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.

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 the combined use of clarithromycin and digoxin is necessary to constantly monitor the concentration of digoxin in the serum, tk. it is possible to increase its concentration and develop potentially lethal arrhythmias.

The simultaneous use of zidovudine in HIV-infected adults and clarithromycin may lead to a decrease Css zidovudine. It is necessary to select doses of clarithromycin and zidovudine.

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-hydroxyclorithromycin by 70%. In patients with creatinine clearance from 30 to 60 ml / min, the dose of clarithromycin should be reduced by 50%.When treating protease inhibitors, do not simultaneously apply clarithromycin in doses over 1 g / day With the simultaneous use of clarithromycin and itraconazole, an increase in the concentrations of clarithromycin and itraconazole in plasma is possible. Careful monitoring of patients simultaneously taking itraconazole and clarithromycin, because of the possibility of enhancing or prolonging the duration of the pharmacological effects of these drugs.

With concurrent administration of clarithromycin (1 g / day) and saquinavir (1200 mg 3 times daily, soft gelatin capsules), there is an increase AUC and Css saquinavir by 177% and 187%, respectively, and clarithromycin by 40%. When these two medicines are used together for a limited time in the doses and dosage forms mentioned above, dose adjustment is not required.