Each film-coated extended-release tablet contains: Ranolazine 500 mg.
Chemical Name: (RS)-N-(2, 6-dimethylphenyl)-2-[4-[2-hydroxy-3-(2-methoxyphenoxy)- propyl]piperazin-1-yl] acetamide.
Pharmacotherapeutic Group: Anti-anginal Drug.
Pharmacology: Ranolazine may have some antianginal effects by inhibition of the late sodium current in cardiac cells. This reduces intracellular sodium accumulation and consequently decreases intracellular calcium overload. Ranolazine, via its action to decrease the late sodium current, is considered to reduce these intracellular ionic imbalances during ischaemia. This reduction in cellular calcium overload is expected to improve myocardial relaxation and thereby decrease left ventricular diastolic stiffness.
Pharmacokinetics: After oral administration of ranolazine, peak plasma concentrations (Cmax) are typically max observed between 2 and 6 hours. Steady state is generally achieved within 3 days of twice-daily dosing. The mean absolute bioavailability of ranolazine after oral administration of immediate-release ranolazine tablets ranged from 35-50%, with large inter-individual variability. There was a 2.5- to 3-fold increase in steady-state AUC as the dose was increased from 500 mg to 1000 mg twice daily. Approximately 62% of ranolazine is bound to plasma proteins. The mean steady-state volume of distribution (Vss) is about 180 l. Ranolazine is eliminated primarily by metabolism. Less than 5% of the dose is excreted unchanged in the urine and faeces. The elimination half-life is about 2-3 hours after intravenous administration. The terminal half-life at steady state after oral administration of ranolazine is about 7 hours, due to the absorption rate-limited elimination.
Ranolazine is indicated as add-on therapy for the symptomatic treatment of patients with stable angina pectoris who are inadequately controlled or intolerant to first-line antianginal therapies (such as beta-blockers and/or calcium antagonists).
Adults: The recommended initial dose of ranolazine is 500 mg twice daily, according to the patient's response, further titrated to a recommended maximum dose of 750 mg twice daily.
If a patient experiences treatment-related adverse events (e.g. dizziness, nausea, or vomiting), down-titration of ranolazine to 375 mg twice daily may be required. If symptoms do not resolve after dose reduction, treatment should be discontinued.
In an oral high-dose tolerability study in angina patients, the incidence of dizziness, nausea, and vomiting increased in a dose-dependent manner. In addition to these adverse events, diplopia, lethargy, and syncope were observed in an intravenous overdose study in healthy volunteers. In the event of overdose, the patient should be closely monitored and the treatment should be symptomatic and supportive. Approximately 62% of ranolazine is bound to plasma proteins, and therefore, complete clearance by haemodialysis is unlikely.
Ranolazine is contraindicated in patients with: Hypersensitivity to the active substance or to any of the excipients.
Severe renal impairment (creatinine clearance <30 ml/min).
Moderate or severe hepatic impairment.
Concomitant administration of potent CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, voriconazole, posaconazole, HIV protease inhibitors, clarithromycin, telithromycin, nefazodone).
Concomitant administration of Class Ia (e.g. quinidine) or Class III (e.g. dofetilide, sotalol) antiarrhythmics other than amiodarone.
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 3080 ml/min).
Patients with low weight (60 kg).
Patients with moderate to severe CHF (NYHA Class III-IV).
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). Renal function decreases with age and it is therefore important to check renal function at regular intervals during treatment with ranolazine. 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.
There are no adequate data from the use of ranolazine in pregnant women. Animal studies are insufficient with respect to effects on pregnancy and embryo foetal development. The potential risk for humans is unknown. Ranolazine should not be used during pregnancy unless clearly necessary.
Lactation: It is unknown whether ranolazine is excreted in human breast milk. The excretion of ranolazine in milk has not been studied in animals. Cartinex should not be used during breast-feeding.
Adverse events like anorexia, decreased appetite, dehydration, anxiety, insomnia, dizziness, headache, blurred vision, visual disturbance, hot flush, hypotension, dyspnoea, cough, epistaxis, constipation, vomiting, nausea, abdominal pain, dry mouth, dyspepsia, flatulence, stomach discomfort, asthenia have been reported.
Ranolazine is a substrate of cytochrome CYP3A4. Inhibitors of CYP3A4 increase plasma concentrations of ranolazine. The potential for dose-related adverse events (e.g. nausea, dizziness) may also increase with increased plasma concentrations. Combining ranolazine with potent CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, voriconazole, posaconazole, HIV protease inhibitors, clarithromycin, telithromycin, nefazodone) is contraindicated. Ranolazine is a substrate for P-gp. Inhibitors of P-gp (e.g. ciclosporin, quinidine, verapamil) increase plasma levels of ranolazine. Careful dose titration of ranolazine is recommended in patients treated with P-gp inhibitors. Ranolazine is partially metabolised by CYP2D6; therefore, inhibitors of this enzyme may increase plasma concentrations of ranolazine. An increase in plasma digoxin concentrations by an average of 1.5-fold has been reported when ranolazine and digoxin are co-administered. Therefore, digoxin levels should be monitored following initiation and termination of ranolazine therapy. There is a theoretical risk that concomitant treatment of ranolazine with other drugs known to prolong the QTc interval may give rise to a pharmacodynamic interaction and increase the possible risk of ventricular arrhythmias. Examples of such drugs include certain antihistamines (e.g. terfenadine, astemizole, mizolastine), certain antiarrhythmics (e.g. quinidine, disopyramide, procainamide), erythromycin, and tricyclic antidepressants (e.g. imipramine, doxepin, amitriptyline).
C01EB18 - ranolazine ; Belongs to the class of other cardiac preparations.
ER tab 500 mg x 3 x 10's.
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