Razine Special Precautions

375 mg tablet: Caution should be exercised when prescribing or up-titrating Ranolazine to patients in whom an increased exposure is expected; concomitant administration of moderate CYP3A4 inhibitors; concomitant administration of P-gp inhibitors; mild hepatic impairment; mild to moderate renal impairment (creatinine clearance 30-80 mL/min); elderly; patients with low weight (≤60 kg); patients with moderate to severe CHF (NYHA Class III-IV). In patients with a combination of these factors, additional exposure increases are expected. Dose-dependent side effects are likely to occur. If Ranolazine is used in patients with a combination of several of these factors, monitoring of adverse events should be frequent, the dose reduced, and treatment discontinued, if needed. The risk for increased exposure leading to adverse events in these different subgroups is higher in patients lacking CYP2D6 activity (poor metabolizers, PM) than subjects with CYP2D6 metabolizing capacity (extensive metabolizers, EM). The above precautions are based on the risk in a CYP2D6 PM patient, and are needed when the CYP2D6 status is unknown. There is a lower need for precautions in patients with CYP2D6 EM status. If the CYP2D6 status of the patient has been determined (e.g. by genotyping) or is previously known to be EM, Ranolazine can be used with caution in these patients when they have a combination of several of the above risk factors.
QT Interval Prolongation: 375 mg tablet: A population-based analysis of combined data from patients and healthy volunteers demonstrated that the slope of the plasma concentration-QTc relationship was estimated to be 2.4 msec per 1000 ng/mL, which is approximately equal to a 2- to 7-msec increase over the plasma concentration range for Ranolazine 500 to 1 g twice daily. Therefore, caution should be observed when treating patients with a history of congenital or a family history of long QT syndrome, in patients with known acquired QT interval prolongation, and in patients treated with drugs affecting the QTc interval.
500 mg tablet: Ranolazine blocks IKr and prolongs the QTc interval in a dose-related manner. Clinical experience in an acute coronary syndrome population did not show an increased risk of pro-arrhythmia or sudden death. However, there is little experience with high doses (>1 g twice daily) or exposure, other QT-prolonging drugs, or potassium channel variants resulting in a long QT interval.
Drug-drug interactions: 375 mg tablet: Co-administration with CYP3A4 inducers is expected to lead to lack of efficacy. Ranolazine should not be used in patients treated with CYP3A4 inducers (e.g. rifampicin, phenytoin, phenobarbital, carbamazepine, St. John's Wort).
Patients with Renal impairment: 375 mg tablet: Renal function decreases with age and it is therefore important to check renal function at regular intervals during treatment with Ranolazine.
Effects on Ability to Drive and Use Machine: No studies on the effects of Ranolazine on the ability to drive and use machines have been performed. Ranolazine may cause dizziness, blurred vision, diplopia, confusional state, and abnormal coordination, hallucination, which may affect the ability to drive and use machines.