Generic Name

Ranolazine

Precaution

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

Indication

Chronic angina

Contra Indication

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

Dose

N/A

Side Effect

>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

Pregnancy Category

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.

Interaction

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.

Pregnancy Category Note

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

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

N/A

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.