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 (see Dosage & Administration and Interactions).
Concomitant administration of P-gp inhibitors (see Dosage & Administration and Interactions).
Mild hepatic impairment (see Dosage & Administration and Pharmacology: Pharmacokinetics under Actions).
Mild to moderate renal impairment (creatinine clearance 30-80 ml/min) (see Dosage & Administration, Adverse Reactions and Pharmacology: Pharmacokinetics under Actions).
Elderly (see Dosage & Administration, Adverse Reactions and Pharmacology: Pharmacokinetics under Actions).
Patients with low weight (≤ 60 kg) (see Dosage & Administration, Adverse Reactions and Pharmacology: Pharmacokinetics under Actions).
Patients with moderate to severe CHF (NYHA Class III-IV) (see Dosage & Administration and Pharmacology: Pharmacokinetics under Actions).
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 metabolisers, PM) than subjects with CYP2D6 metabolising capacity (extensive metabolisers, EM) (see Pharmacology: Pharmacokinetics under Actions). 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, Ranexa can be used with caution in these patients when they have a combination of several of the above 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 1000 ng/ml, which is approximately equal to a 2- to 7-msec increase over the plasma concentration range for ranolazine 500 to 1000 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 (see Interactions).
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 (e.g. rifampicin, phenytoin, phenobarbital, carbamazepine, St. John's Wort) (see Interactions).
Lactose: Ranexa 750 mg contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency, or glucose- galactose malabsorption should not take this medicinal product.
Azo colouring agent E102: Ranexa 750 mg contains the azo colouring agent E102 which may cause allergic reactions.
Effects on ability to drive and use machines: 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, coordination abnormal, hallucination (see Adverse Reactions), which may affect the ability to drive and use machines.
Renal impairment: Renal function decreases with age and it is therefore important to check renal function at regular intervals during treatment with ranolazine (see Dosage & Administration, Contraindications, Adverse Reactions and Pharmacology: Pharmacokinetics under Actions).