Ranolazine

Indications

Ranolazine is used for: Chronic angina

Adult Dose

Oral Chronic angina 500 mg PO BID initially; may increase to 1,000 mg PO BID, if needed Hepatic Impairment: Mild: Dose titration needed. Moderate to severe: Contraindicated.

Child Dose

Renal Dose

Renal Impairment Mild to moderate (CrCl 30-80 mL/min): Dose titration needed. Severe (CrCl <30 mL/min): Contraindicated.

Administration

May be taken with or without food.

Contra Indications

Taking strong inhibitors of CYP3A (e.g., ketoconazole, clarithromycin, nelfinavir) Taking inducers of CYP3A (e.g., phenobarbital, rifampicin)Significant hepatic impairment

Precautions

Heart rhythm problems (e.g., bradycardia, QT prolongation, ventricular tachycardia), liver problems, certain uncorrected mineral imbalances (low potassium/magnesium levels), severe kidney problems. Lactation: Unknown if excreted in breast milk; discontinue or do not nurse

Pregnancy-Lactation

Pregnancy category: C Lactation: Unknown if excreted in breast milk; discontinue or do not nurse

Interactions

Increased plasma levels w/ moderate CYP3A4 inhibitors (e.g. diltiazem, fluconazole, erythromycin), P-glycoprotein inhibitors (e.g. verapamil, ciclosporin) and CYP2D6 inhibitors (e.g. paroxetine). May increase plasma digoxin concentrations. May increase risk of rhabdomyolysis w/ simvastatin. May increase plasma concentrations of atorvastatin, other statins (e.g. lovastatin) and CYP3A4 substrates w/ narrow therapeutic range (e.g. tacrolimus, sirolimus, everolimus). May increase plasma exposure of metformin. Increased risk of ventricular arrhythmias w/ other drugs that prolong QT interval (e.g. terfenadine, astemizole, mizolastine). Potentially Fatal: Increased plasma concentrations leading to increased adverse effects w/ CYP3A4 inhibitors (e.g. itraconazole, ketoconazole, HIV protease inhibitors, clarithromycin, telithromycin, nefazodone). Decreased plasma concentration w/ CYP3A4 inducers (e.g. rifampicin, phenytoin, phenobarbital, carbamazepine). Increased risk of QT interval prolongation w/ class 1A (e.g. quinidine) or class III (e.g. dofetilide, sotalol) antiarrhythmics other than amiodarone.

Side Effects

Side effects of Ranolazine : >10% Dizziness (5-13%) 1-10% Nausea (4-9%), Constipation (5-8%), Headache (3-6%), Syncope (3%) Frequency Not Defined Palpitations, Bradycardia, Peripheral edema, Prolonged QT interval, Abdominal pain, Dry mouth, Dyspepsia, Anorexia, Vomiting, Hematuria, Dyspnea, Tinnitus, Vertigo, Blurred vision, Vasovagal syncope, Confusional state, Hematuria, Hyperhidrosis

Mode of Action

Ranolazine exert its antianginal and anti-ischaemic effects through concentration-, voltage-, and frequency-dependent inhibition of the late Na current and other cardiac ion channels and transporters. It may decrease the magnitude of the late Na current resulting in a net reduction in intracellular Na concentrations, reversal of Ca overload, restoration of ventricular pump function, and prevention of ischaemia-induced arrhythmias. Its antianginal effects are not dependent upon reductions in heart rate or BP and QT interval prolongation effect is caused by inhibition of rapid delayed rectifier K current (IKr), which prolongs the ventricular action potential.