What are the side effects of Ranolazine?

Side Effects of Ranolazine

Ranolazine commonly causes constipation, nausea, dizziness, and headache as its major adverse effects, with a dose-dependent QT interval prolongation that requires monitoring, especially in patients with risk factors for arrhythmias. Patients should be informed about these common side effects and monitored for QT prolongation, particularly when taking other medications that affect the QT interval or in those with hepatic or renal impairment. 1

Common Side Effects

• Constipation 1, 2
• Nausea 1, 2
• Dizziness 1, 2
• Headache 1, 2
• Vomiting 1, 3

Cardiovascular Effects

• QT interval prolongation (dose-dependent) 1
  • Usually not requiring dose reduction in clinical trials 1
  • May increase risk of torsades de pointes 3
• Minimal effects on heart rate and blood pressure 1

Special Populations and Risk Factors

Renal Impairment

• Increased exposure (up to 2-fold) with advancing degrees of renal impairment 4
• Limit dose to 500 mg twice daily in patients with severe renal impairment (CrCl <30 ml/min) 1, 5
• Case reports of severe neurologic adverse effects in elderly patients with renal impairment 5

Hepatic Impairment

• Contraindicated in patients with hepatic impairment or liver cirrhosis 1
• Risk of drug accumulation due to reduced metabolism 1

Elderly Patients

• May be at higher risk for adverse effects 5
• Consider lower doses (500 mg twice daily) in patients over 80 years 5

Drug Interactions

QT-Prolonging Medications

• Increased risk of QT prolongation when combined with other QT-prolonging drugs 2, 3

CYP3A4 Inhibitors/Substrates

• Ranolazine is extensively metabolized by CYP3A enzymes 4
• Significant interactions with:
  • Ketoconazole (increases ranolazine exposure 3.9-fold) 4
  • Diltiazem (increases ranolazine exposure 1.5-fold) 4
  • Verapamil (increases ranolazine exposure 2-fold) 4

P-glycoprotein Substrates

• Increases digoxin concentration by 40-60% through P-glycoprotein inhibition 1, 4
• Should be used with caution in patients taking digoxin 1

Other Interactions

• Limit grapefruit and grapefruit juice consumption (can increase blood levels) 2
• Weak inhibitor of CYP3A (increases simvastatin exposure <2-fold) 4

Monitoring Recommendations

• ECG monitoring for QT prolongation in high-risk patients 1, 2
• Renal function in patients with kidney disease 2, 5
• Signs of neurologic adverse effects, especially in elderly patients with renal impairment 5
• Digoxin levels when co-administered 1

Contraindications

• Hepatic impairment or liver cirrhosis 1
• Concomitant use of strong CYP3A inhibitors 2
• Congenital long QT syndrome or family history of long QT syndrome 2
• Severe renal impairment (use with caution and dose reduction) 1, 5

Ranolazine should be started at 500 mg orally twice daily and can be uptitrated to a maximum of 1000 mg orally twice daily as needed for symptom control and as tolerated 1.