Ranolazine

Oral
Stable angina

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

Mild: Dose titration needed. Moderate to severe: Contraindicated.

May be taken with or without food.

Concomitant admin w/ potent CYP3A4 inhibitors, CYP3A4 inducers and class 1A or class III antiarrhythmics other than amiodarone. Moderate to severe hepatic and severe renal impairment (CrCl <30 mL/min).

Patient w/ history of long QT syndrome, known acquired QT interval prolongation, moderate to severe CHF (NYHA Class III-IV), low wt (<60 kg). Mild hepatic and mild to moderate renal impairment (CrCl 30-80 mL/min). Elderly. Pregnancy and lactation.

QT interval prolongation, acute renal failure, nausea, constipation, dizziness, headache, palpitations, tinnitus, vertigo, dry mouth, abdominal pain, vomiting, peripheral oedema, dyspnoea, bradycardia, haematuria, paraesthesia, hypotension, blurred vision.

PO: C

May impair ability to drive or operate machinery.

Baseline and follow up ECG to evaluate QT interval; monitor renal function in patients w/ moderate to severe renal impairment, BP in patients w/ renal dysfunction; serum K levels.

Symptoms: Dizziness, nausea, vomiting, diplopia, lethargy, syncope, severe tremor, incoordination, dysplasia, hallucination. Management: Symptomatic and supportive treatment.

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.

Increased plasma concentrations w/ grapefruit juice. Decreased plasma concentrations w/ St John's wort.

Description:
Mechanism 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 (I_Kr), which prolongs the ventricular action potential.
Pharmacokinetics:
Absorption: Highly variable. Time to peak plasma concentration: Approx 2-5 hr.
Distribution: Plasma protein binding: Approx 62%.
Metabolism: Extensively metabolised in GI tract and liver by CYP3A4 (major) and CYP2D6 (minor) isoenzymes.
Excretion: Via urine (approx 75%) and the remainder in faeces (<5% as unchanged drug). Terminal half-life: 7 hr.

Store at 25°C.

Anti-Anginal Drugs

Anon. Ranolazine. Lexicomp Online. Hudson, Ohio. Wolters Kluwer Clinical Drug Information, Inc. https://online.lexi.com. Accessed 05/08/2014.

Buckingham R (ed). Ranolazine. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/08/2014.

McEvoy GK, Snow EK, Miller J et al (eds). Ranolazine. AHFS Drug Information (AHFS DI) [online]. American Society of Health-System Pharmacists (ASHP). https://www.medicinescomplete.com. Accessed 05/08/2014.

Ranexa Extended-Release Tablets. U.S. FDA. https://www.fda.gov/. Accessed 05/08/2014.

Ranexa Tablet, Film Coated, Extended Release (Gilead Sciences, Inc.). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/. Accessed 05/08/2014.