Common Side Effects of Ranolazine
The most common side effects of ranolazine include dizziness (6.2%), headache (5.5%), constipation (4.5%), and nausea (4.4%), with dizziness potentially being dose-related. 1
Primary Side Effect Profile
Ranolazine's side effect profile can be categorized as follows:
Very Common Side Effects (>4%)
- Dizziness (6.2%)
- Headache (5.5%)
- Constipation (4.5%)
- Nausea (4.4%)
Common Side Effects (0.5-4%)
- Cardiovascular: Bradycardia, palpitations
- Neurological: Syncope (vasovagal)
- Gastrointestinal: Abdominal pain, dry mouth, vomiting, dyspepsia
- General: Asthenia (weakness), peripheral edema
- Sensory: Tinnitus, vertigo, blurred vision
- Respiratory: Dyspnea
- Metabolic: Anorexia
- Psychiatric: Confusional state
- Renal: Hematuria
- Skin: Hyperhidrosis
- Vascular: Hypotension, orthostatic hypotension 1
QT Interval Prolongation
Ranolazine prolongs the QTc interval in a dose-dependent manner. This requires:
- Baseline ECG evaluation
- Periodic ECG monitoring during dose adjustments
- Avoidance in patients with pre-existing QT prolongation or long QT syndrome 2
Despite QT prolongation, clinical trials have not demonstrated increased risk of proarrhythmic effects at recommended therapeutic doses 1.
Special Considerations
Drug Interactions
- Ranolazine is extensively metabolized by CYP3A enzymes
- Contraindicated with:
- Strong CYP3A inhibitors
- CYP3A inducers
- Liver cirrhosis 1
- Increases digoxin concentration - requires caution when co-administered 3
Renal Effects
- Produces small elevations of serum creatinine (approximately 0.1 mg/dL)
- This is due to inhibition of creatinine's tubular secretion rather than impaired kidney function
- The elevation has rapid onset, doesn't progress during therapy, and is reversible after discontinuation 1
- More significant increases in serum creatinine with BUN or potassium elevation may indicate acute renal failure in patients with severe renal impairment 1
Postmarketing Reports
Several additional adverse effects have been reported during post-approval use:
- Neurological: Abnormal coordination, myoclonus, paresthesia, tremor
- Metabolic: Hypoglycemia in diabetic patients on antidiabetic medication
- Psychiatric: Hallucinations
- Renal: Dysuria, urinary retention
- Skin: Angioedema, pruritus, rash 1
Management of Common Side Effects
Dizziness
- Caution patients about operating machinery or driving, especially when starting therapy
- May be dose-related, consider dose reduction if severe 2
Constipation
- Increase fluid intake and dietary fiber
- Consider mild laxatives if persistent 2
Nausea
- Take medication with food
- Consider antiemetics if severe 2
Discontinuation Rates
At recommended doses, approximately 6% of patients discontinue ranolazine due to adverse events compared to 3% on placebo. The most common reasons for discontinuation include:
- Dizziness (1.3% vs 0.1% for placebo)
- Nausea (1% vs 0%)
- Asthenia, constipation, and headache (each about 0.5% vs 0%) 1
Doses above 1000 mg twice daily are poorly tolerated 1.