With the joint reception of clarithromycin with drugs, primarily metabolized by isoenzyme CYP3A, there may be a mutual increase in their concentrations, which can enhance or prolong both the therapeutic and side effects. Contraindicated joint administration with astemizole, cisapride, pimozide, terfenadine, ergotamine and other ergot alkaloids, alprazolam, midazolam, triazolam.
Caution is prescribed with carbamazepine, cilostazolum, cyclosporine, disopyramide, lovastatin, simvastatin, methylprednisolone, ranitidine, indirect anticoagulants (eg, warfarin), quinidine, rifabutin, sildenafil, tacrolimus, vinblastine, phenytoin, theophylline, valproic acid, cilostazol (metabolized via other cytochrome P450 isoenzymes); this can lead to an increase in the concentration in the plasma of the latter. It is necessary to adjust the dose of the drug and monitor the concentration of these drugs in the blood plasma.
Simultaneous use of clarithromycin with cisapride, pimozide, terfenadine, astemizole, quinidine, disopyramide leads to an increase in the plasma level of these drugs (2-3 times) in the blood, which may be accompanied by an extension of the interval QT, the development of life-threatening ventricular arrhythmias: ventricular tachycardia, including "pirouette" type, fibrillation and flutter of the ventricles, ventricular fibrillation. It is necessary to monitor the ECG and serum concentrations of these drugs.
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 its therapeutic effect, and, at the same time, increase the concentration of 14 (R) -hydroxyclamirithromycin.
With the simultaneous use of fluconazole at a dose of 200 mg daily and clarithromycin at a dose of 1 g per day, an increase in the equilibrium concentrationCss) and the area under the curve "concentration-time" (AUC) of clarithromycin 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, the metabolism of clarithromycin is significantly slowed down: CmOh clarithromycin is increased by 31%, Css - by 181%, AUC - by 77%; the process of formation of 14-hydroxyclarithromycin is significantly slowed down. For patients with CRF, correction of the dose of clarithromycin is necessary: with a clearance of creatinine from 30 to 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 together with clarithromycin in a dose exceeding 1 g per day.
When using clarithromycin with omeprazole, ranitidine: despite the possibility of increasing their plasma concentration, there is no need to reduce the doses of omeprazole or ranitidine. So, when taking clarithromycin and omeprazole CmOh, AUC and T1/2 omeprazole can increase 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 using clarithromycin with sildenafin, taladafil 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,carbamazepine: the elimination of theophylline and carbamazepine is slowed, the concentration of the latter in the systemic circulation may be increased, and theophylline intoxication may develop; it is possible to enhance the effects of carbamazepine.
When using clarithromycin with tolterodine in patients with low isoenzyme activity CYP2D6, a dose reduction of tolterodine in the presence of clarithromycin (an inhibitor of isoenzymes CYP3A).
In the case of combined 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, as well as other benzodiazepines, which are metabolized by the isoenzyme CYP3A (triazolam and alprazolam). When using clarithromycin and midazolam (IV), a dose adjustment may be required. The same precautions should be applied to other benzodiazepines metabolized by isoenzyme CYP3A. For benzodiazepines, the excretion of which does not depend on the isoenzyme CYP3A (temazepam, nitrazepam, lorazepam), clinically significant interaction with clarithromycin is unlikely.
When using clarithromycin with colchicine: clarithromycin, like other macrolides, inhibiting CYP3A and P-glycoprotein, can enhance 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, an increase in the concentration of digoxin in the blood is possible, which may lead to an increase in both the therapeutic and side effects of digoxin, including the development of potentially fatal arrhythmias. The concentration of digoxin in the serum should be carefully monitored.
Simultaneous reception of clarithromycin and zidovudine in adult HIV-infected patients can lead to a decrease in the equilibrium concentration and Css zidovudine in the blood. Because the clarithromycin affects the absorption of zidovudine, taking these two drugs should be divided in time with an interval of 1-2 hours. It is necessary to select the 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-hydroxyclarithromycin by 70%. In patients with a 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 these two drugs are co-administered for a limited time in the doses and dosage forms mentioned above, dose adjustment is not required. With a joint admission with verapamil possible lowering of blood pressure, bradyarrhythmia and lactic acidosis.
Clarithromycin increases the concentration of inhibitors of hydroxymethylglutaryl-CoA (HMG-CoA) reductase (lovastatin, simvastatin or others): rare cases of rhabdomyolysis have been described.
With the combined use of clarithromycin with warfarin (or other indirect anticoagulants), the effect of warfarin may be enhanced; it is necessary to periodically monitor prothrombin time.
When used with hypoglycemic drugs, including with insulin, in rare cases, the development of hypoglycemia is possible.
Interaction with oral contraceptives is not revealed.