With the simultaneous administration of clarithromycin and drugs primarily metabolized by the CYP3A isoenzyme, a mutual increase in their concentrations is possible, which may enhance or prolong both the therapeutic and side effects.
Contraindicated joint use with astemizole, cisapride, pimozide, terfenadine, ergotamine and other ergot alkaloids, as well as with lovastatin and simvastatin.
Preparations that are inducers of CYP3A (for example, phenobarbital and St. John's wort pitted) can induce the metabolism of clarithromycin. This can lead to a subtherapeutic level of clarithromycin, which leads to a decrease in its effectiveness. Assign with caution to carbamazepine, cilostazolum, cyclosporine, disopyramide, methylprednisolone, omeprazole, indirect anticoagulants (including warfarin), quinidine, rifabutin, sildenafil, tacrolimus, vinblastine, as well as phenytoin, theophylline and valproic acid (metabolized via cytochrome P450 isoenzymes).
Apply with caution to alprazolam, triazolam, midazolam for intravenous administration. It is necessary to correct the dose of the drug and monitor the concentration in the blood.
When combined with cisapride, pimozide, terfenadine and astemizole, it is possible to increase the concentration of the latter in the blood, increase the QT interval, the occurrence of arrhythmia, including ventricular tachycardia, including.type "pirouette" and ventricular fibrillation.
When combined with ergotamine and dihydroergotamine, acute poisoning with drugs of the ergotamine group (vascular spasm, ischemia of the extremities and other tissues, including the central nervous system) is possible.
Efavirenz, nevirapine, rifampicin, rifabutin and rifapentin (inducers of cytochrome P450) reduce the level of clarithromycin in the plasma and weaken the therapeutic effect of the latter, and, at the same time, increasing the level 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 of Css and AUC of clarithromycin is possible by 33% and 18%, respectively. Correction of the dose of clarithromycin is not required. With the simultaneous administration of ritonavir 600 mg / day and clarithromycin 1 g / day, a decrease in the metabolism of clarithromycin (an increase in CmOh by 31%, Css by 182% and AUC by 77%), complete suppression of the formation of 14-hydroxyclarithromycin. In patients with chronic renal failure, dose adjustments are necessary: with creatinine clearance (CK) of 30-60 ml / min, the dose of clarithromycin should be reduced by 50%, with a CK of 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. It requires ECG monitoring (increasing the QT interval), serum concentrations of these drugs. Clarithromycin increases concentrations of HMG-CoA reductase inhibitors (lovastatin, simvastatin). Perhaps the development of rhabdomyolysis in patients taking these drugs together.
When using clarithromycin and omeprazole, an increase in CmOh, AUC and half-life of 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 use of clarithromycin and indirect anticoagulants, the effect of the latter is possible. When used simultaneously with warfarin and other indirect anticoagulants, it is necessary to monitor the international normalized ratio and prothrombin time.
When using 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 sildenafil, tadalafil and vardenafil.
With the combined use of clarithromycin with theophylline and carbamazepine, an increase in the concentration of the latter in the systemic circulation is possible.
When clarithromycin with tolterodine is used in patients with a low level of metabolism via CYP2D6, a dose reduction of tolterodine in the presence of clarithromycin (inhibitor CYP3A) may be required.
With the simultaneous use of clarithromycin (1 g / day) with midazolam (oral), an increase in the AUC of midazolam is 7-fold. When using midazolam (intravenous) and clarithromycin, a dose adjustment may be required. The same precautions should also be applied to other benzodiazepines that are metabolized by CYP3A. For benzodiazepines, the excretion of which does not depend on 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).
With the joint administration of clarithromycin and digoxin, the concentration of digoxin in the serum should be carefully monitored (possibly increasing its concentration and the development of potentially fatal arrhythmias). Simultaneous reception of clarithromycin and zidovudine by adult HIV-infected patients can lead to a decrease in Cs 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), an increase in Atazanavir AUC by 28%, clarithromycin by a factor of 2, and a decrease in AUC of 14-hydroxyclarithromycin by 70%. In patients with CK 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 in AUC and Css of saquinavir is possible by 177% and 187%, respectively, and clarithromycin by 40%. When the two medicines are co-administered for a limited time in the doses / dosage forms mentioned above, dose adjustment is not required. With a joint admission with verapamil possible lowering of blood pressure, bradyarrhythmia and lactic acidosis.
With the simultaneous use of clarithromycin and oral hypoglycemic agents, including insulin, in rare cases, the development of hypoglycemia is possible. A careful control of the concentration of glucose in the blood is recommended.
With simultaneous reception with clarithromycin (500 mg 2 times a day) etravirine reduces the concentration of clarithromycin in plasma by 53% and increases the concentration of the active metabolite, 14-hydroxyclarithromycin, by 46%. Since 14-hydroxyclatromycin has a reduced activity against Mycobacterium avium complex (MAC), the overall activity of clarithromycin and its metabolite against this pathogen may change.