What are the side effects of Ranolazine?

Ranolazine Side Effects

The most common side effects of ranolazine include dizziness, headache, constipation, and nausea, with QT interval prolongation being a serious potential cardiac concern requiring monitoring. 1

Common Side Effects

Ranolazine's most frequently reported adverse effects include:

• Dizziness
• Headache
• Constipation
• Nausea 1, 2

Less common but reported side effects include:

• Asthenia (weakness) 3
• Lightheadedness 1

Serious Cardiac Side Effects

QT Interval Prolongation

• Ranolazine causes dose-related QT interval prolongation 1, 4
• This can potentially lead to torsades de pointes, a life-threatening ventricular arrhythmia 4
• ECG monitoring is recommended, especially when initiating therapy or adjusting doses 4
• Patients should report symptoms such as feeling faint, lightheaded, or experiencing irregular/fast heartbeats 1

Drug Interactions Affecting Cardiac Safety

• Ranolazine should not be used with medications that significantly prolong the QT interval (e.g., dofetilide) 4
• As a moderate CYP3A4 inhibitor and P-glycoprotein inhibitor, ranolazine can increase plasma concentrations of certain drugs, enhancing QT-prolonging effects 4

Renal Effects

• Cases of kidney failure have been reported, particularly in patients with pre-existing severe kidney problems 1
• A case report described BRASH syndrome variant (Bradycardia, Renal failure, AV nodal blockade, Shock, and Hyperkalemia) associated with ranolazine use 5
• Dose adjustment is recommended for patients with renal impairment 6

Neurologic Side Effects

• Rare but significant neurologic adverse effects have been reported, particularly in elderly patients with renal impairment 6
• These include dysarthria, dysmetria, hallucinations, worsening tremors, and difficulty with word finding 6
• Doses greater than 500 mg twice daily should be avoided in patients older than 80 years or those with creatinine clearance less than 30 ml/minute 6

Contraindications and Precautions

Ranolazine is contraindicated in patients:

• Taking strong CYP3A inhibitors (ketoconazole, itraconazole, clarithromycin, nefazodone, HIV protease inhibitors) 1
• Taking CYP3A inducers (rifampin, rifabutin, rifapentine, phenobarbital, phenytoin, carbamazepine, St. John's wort) 1
• With liver cirrhosis 1
• With pre-existing QT prolongation or congenital long QT syndrome 4

Special Populations at Risk

Increased monitoring is recommended for:

• Elderly patients 6
• Patients with renal impairment 6
• Patients with electrolyte abnormalities (hypokalemia, hypomagnesemia) 4
• Patients with bradycardia or heart failure 4
• Female patients (higher risk of QT-related arrhythmias) 4

Dosing Considerations to Minimize Side Effects

• Starting dose: 500 mg orally twice daily 4
• Maximum dose: 1000 mg orally twice daily 4
• Lower doses should be considered for elderly patients and those with renal impairment 6
• Avoid grapefruit and grapefruit juice as they can increase blood levels of ranolazine 1

Monitoring Recommendations

• Baseline ECG to evaluate QTc interval 4
• Regular ECG monitoring, especially after dose adjustments 4
• Electrolyte monitoring (particularly potassium and magnesium) 4
• Renal function tests in at-risk patients 4
• Symptom assessment for side effect management 4

By understanding these side effects and implementing appropriate monitoring strategies, the risks associated with ranolazine therapy can be minimized while maintaining its antianginal benefits.