ranolazine (Ranexa)

Indications

• adjuvant therapy of chronic angina pectoris after other options exhausted
• rhythm control in atrial fibrillation
  • may accelerate chemical cardioconversion with amiodarone in patients with recent-onset atrial fibrillation

Contraindications

• pre-existing QT prolongation
• hepatic insufficiency (Child-Pugh classes A,B,C)
• coadministration of drugs that prolong QT interval
• no benefit for acute onset coronary artery disease
• no benefit for patients with incomplete revascularization after PCI

Pregnancy category: C

Dosage

• start 500 mg PO BID
• titrate to maximum dose of 1000 mg BID

Tabs: 500 (orange)

Pharmacokinetics

• metabolized by cyt P450 3A4 & to a lesser extent cyt P450 2D6

Monitor

ECG, baseline and follow-up

Adverse effects

• increased QT interval
• dizziness (6%), headache (6%), constipation (4%), nausea (4%)
• others < 2%
  • palpitations, tinitus, vertigo, abdominal pain, xerostomia, vomiting, peripheral edema, dyspnea

Drug interactions

• drugs that inhibit cyt P450 3A4 increase ranolazine levels (diltiazem, verapamil, HIV protease inhibitors, macrolides)
• drugs that inhibit cyt P450 2D6 do not increase ranolazine levels significantly
• ranolazine inhibits cyt P450 3A4 & cyt P450 2D6, thus may increase levels of drugs metabolized by these enzymes (simvastatin levels doubled)
• ranolazine inhibits P-glycoprotein and may increase levels of drugs eliminated in part by P-glycoprotein (digoxin levels increased 1.5 fold)
• avoid other drugs that prolong QT interval (amiodarone, erythromycin, quinidine, sotalol, etc)

Mechanism of action

• inhibits late myocyte Na+ current
• no significant effect on heart rate or blood pressure
• facilitates myocardium functioning during ischemia
  • reduces intracellular Na+ & Ca+2 during myocardial ischemia
  • partially inhibits fatty acid oxidation, thus increases glucose oxidation
  • may decrease myocardial oxygen demand
• inhibits P-glycoprotein

More general terms

• metabolic agent (metabolic modifier)