Atorvastatin simultaneous use of ranolazine 1000 mg 2 times a day and atorvastatin 80 mg 1 time per day increases the of atorvastatin 1.4 and 1, 3 times, respectively, atorvastatin metabolites vary by no more than 35%. With simultaneous use of ranolazine and atorvasta slime may require dose reduction of atorvastatin and conduct appropriate clinical monitoring. For other statins metabolized with the participation of isoenzyme (lovastatin), you may need a dose adjustment. Tacrolimus, cyclosporine, sirolimus, everolimus Increased plasma concentrations of tacrolimus, substrate isoenzyme, was noted in patients on treatment with ranolazine. With simultaneous application of tacrolimus and ranolazine it is recommended to monitor the plasma concentrations of tacrolimus and, if necessary, carry out adjustment of the dose. This approach is recommended for other substrates of masteron 100 with narrow therapeutic range (eg, cyclosporine, sirolimus, everolimus). Substrates conveyor organic cations 2 With simultaneous use of ranolazine 500 mg and 1000 mg 2 times daily and metformin 1000 mg 2 times a day of metformin plasma concentrations in patients with type 2 diabetes is increased 1.4 and 1.8 times, respectively. Perhaps an increase in plasma concentrations of other substrates OST2, including pindolol and varenicline, while the use of ranolazine.
Renal impairment For patients with renal insufficiency, mild or moderate (creatinine clearance 30-80 ml / min), the dose titration is recommended. Is contraindicated in patients with renal-severe impairment (creatinine clearance <30 mL / min). Taking into account the possibility of reducing kidney function with age, in patients with middle and old age should regularly monitor assessment of renal function during long-term . hepatic impairment For patients with hepatic insufficiency mild (5-6 points on a scale Child-Pugh) recommended dose titration. Is contraindicated in patients with hepatic insufficiency, the mean (7-9 points on a scale Child-Pugh) or severe (more than 9 points on a scale Child-Pugh) severity. Older age (over 65 years) Elderly patients may be a strengthening due to age-related decrease in renal function. There is increased incidence of side effects. Body weight (less than 60 kg) Dose selection for patients weighing less than 60 kg must be carried out with caution, as cases of adverse events in these patients were more common. Chronic heart failure Dose selection for patients with moderate or severe heart failure severity should be performed with caution. It is necessary to carry out regular monitoring of side effects, if necessary, should be reduced dose or refused treatment. Analysis of pooled data from studies of patients and healthy volunteers showed that the dependence of the duration of the QTc interval of the plasma concentration , which is approximately 2 to increase to 7 ms for a range of concentrations in plasma corresponding to a dose of 500 to 1000 mg of ranolazine, received 2 times per day. Therefore, caution should be exercised when treating patients with a syndrome of congenital prolongation in the history of the presence of QT prolongation in the family history, patients with known acquired , and in patients receiving treatment with drugs that affect the interval . Insufficient activity of isoenzyme : risk of increased incidence of side effects in these groups is increased in patients with insufficient activity isoenzyme (patients with “slow” metabolism) compared with patients with normal ability to metabolize isoenzyme (with “fast” metabolism of the patients). Precautions are designed taking into account the risk for patients with a “slow” metabolism isoenzyme and are necessary in case the status of the isoenzyme metabolism is unknown. For patients with a “fast” isozyme metabolism no need for such precautions. Patients diagnosed with (eg by genotyping) or previously known intense status metabolism isoenzyme should be used with caution if the patient has a combination of several of the above risk factors. Effects on ability to drive vehicles and mechanisms studies on the effect on the ability to drive vehicles and management mechanisms are not carried out. Given the possibility of side effects such as dizziness, blurred vision, double vision, confusion, impaired coordination of movements and hallucinations, caution should be exercised in the management of vehicles and mechanisms, as well as classes of potentially hazardous activities that require high concentration and speed of psychomotor reactions .