Ranexa Special Precautions

Caution should be exercised when prescribing or uptitrating ranolazine to patients in whom an increased exposure is expected: Concomitant administration of moderate CYP3A4 inhibitors and P-gp inhibitors; mild hepatic impairment; mild to moderate renal impairment (CrCl 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 Ranexa 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 previously mentioned 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 (eg, by genotyping) or is previously known to be EM, Ranexa can be used with caution in these patients when they have a combination of several of the previously mentioned risk factors.
QT Prolongation: 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 1,000 ng/mL, which is approximately equal to a 2- to 7-msec increase over the plasma concentration range for ranolazine 500-1,000 mg 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.
Drug-Drug Interactions: Co-administration with CYP3A4 inducers is expected to lead to lack of efficacy. Ranexa should not be used in patients treated with CYP3A4 inducers (eg, rifampicin, phenytoin, phenobarbital, carbamazepine, St. John's wort).
Renal Impairment: Renal function decreases with age and it is therefore important to check renal function at regular intervals during treatment with ranolazine.
Effects on the Ability to Drive or Operate Machinery: No studies on the effects of Ranexa on the ability to drive and use machines have been performed. Ranexa may cause dizziness, blurred vision, diplopia, confusional state, abnormal coordination, hallucination, which may affect the ability to drive and use machines.
Impairment of Fertility: In animals, reproduction studies indicated no adverse effects on fertility. The effect of ranolazine on human fertility is unknown.
Use in children: The safety and efficacy of Ranexa in children <18 years have not been established. No data are available.