Can Ranexa (ranolazine) cause tremors?

Can Ranexa (Ranolazine) Cause Tremors?

Yes, ranolazine can cause tremors, though this is an uncommon adverse effect that occurs in less than 0.5% of patients. 1

Evidence from FDA Drug Labeling

The FDA-approved prescribing information for ranolazine explicitly lists tremor as a potentially medically important adverse reaction observed more frequently with ranolazine than placebo in controlled studies, occurring at a rate of <0.5%. 1

Clinical Context and Risk Factors

Tremors associated with ranolazine are part of a broader spectrum of neurologic adverse effects that include: 1

• Paresthesia (tingling/numbness)
• Hypoesthesia (decreased sensation)
• Abnormal coordination
• Myoclonus
• Other serious neurologic events

High-Risk Populations

Elderly patients with renal impairment are at substantially increased risk for neurologic adverse effects including tremors. 2 A documented case report describes an 81-year-old woman with renal impairment who developed worsening tremors (along with dysarthria, dysmetria, and hallucinations) approximately 48 hours after a ranolazine dose increase, with symptoms resolving 2 days after discontinuation. 2

Mechanism and Dose Relationship

The neurologic adverse effects, including tremors, appear to be: 2

• Dose-related: Often associated with dose increases or elevated drug exposure
• Concentration-dependent: Related to ranolazine's activity at muscle and neuronal sodium channels
• Reversible: Many patients report symptom resolution following drug discontinuation or dose decrease 1

Clinical Recommendations

If tremors develop on ranolazine therapy:

1. Consider dose reduction first - particularly if the patient is on 1000 mg twice daily, as doses above this are poorly tolerated 1

2. Evaluate for risk factors: 1, 2

   • Renal impairment (CrCl <60 mL/min)
   • Advanced age (>80 years)
   • Baseline neurologic disease
   • Concomitant CYP3A inhibitors (diltiazem, verapamil, erythromycin)

3. Limit dose to 500 mg twice daily in patients with moderate renal impairment (CrCl 30-60 mL/min) or those on moderate CYP3A inhibitors 1

4. Discontinue ranolazine if tremors are accompanied by other serious neurologic symptoms (confusion, coordination problems, hallucinations) 1, 2

5. Do NOT use ranolazine in patients with severe renal impairment (CrCl <30 mL/min), as drug accumulation significantly increases the risk of neurologic adverse effects 1, 2

Important Caveat

While tremor is listed as a known adverse effect in the FDA labeling, it remains relatively uncommon compared to the more frequent adverse effects of dizziness (6.2%), headache (5.5%), constipation (4.5%), and nausea (4.4%). 1 However, the potential for serious neurologic complications, particularly in vulnerable populations, warrants careful monitoring and appropriate dose adjustments.