Does Ranexa (ranolazine) cause hypotension?

Does Ranolazine Cause Hypotension?

Ranolazine can cause hypotension and orthostatic hypotension, though these are uncommon adverse effects occurring at an incidence of less than 0.5% in clinical trials. 1

Mechanism of Action and Hemodynamic Effects

• Ranolazine works primarily through inhibition of the late sodium current (late INa), which prevents intracellular calcium overload during ischemia 2
• Unlike many other antianginal medications, ranolazine has a neutral hemodynamic profile, exerting its antianginal effects without significantly affecting heart rate or blood pressure 2, 3
• This neutral hemodynamic profile makes ranolazine potentially useful in cases of bradycardia and/or hypotension where other antianginal agents might worsen these conditions 4

Clinical Evidence of Hypotensive Effects

• According to the FDA drug label, hypotension and orthostatic hypotension are listed as adverse reactions occurring at an incidence of less than 0.5% in patients treated with ranolazine 1
• In controlled clinical trials, ranolazine was generally well tolerated with no overt effects on cardiovascular hemodynamics or conduction, apart from a modest increase in QT interval 3
• The most common adverse events leading to discontinuation of ranolazine were dizziness (1.3% vs 0.1% for placebo), nausea (1% vs 0%), asthenia, constipation, and headache (each about 0.5% vs 0%) 1

Monitoring and Precautions

• When prescribing ranolazine, be aware that it may interact with other medications that can affect blood pressure
• Ranolazine should be used with caution when co-administered with drugs that have SA and/or AV nodal-blocking properties 4
• Monitor patients for symptoms of hypotension, particularly when initiating therapy or increasing the dose
• Elderly patients and those with pre-existing cardiovascular conditions may be more susceptible to hypotensive effects

Clinical Context and Considerations

• Ranolazine is contraindicated in patients with hepatic impairment or liver cirrhosis 4, 2
• Ranolazine increases digoxin concentration and should be used with caution in patients taking digoxin 4
• The drug is generally administered as 500 mg twice daily initially, with the option to increase to 1000 mg twice daily as needed 1
• Doses above 1000 mg twice daily are poorly tolerated 1

Special Populations

• Patients with diabetes and chronic stable angina might benefit from ranolazine treatment, as it has been shown to reduce glycated hemoglobin levels 4, 2
• Patients with left ventricular hypertrophy might experience greater efficacy with ranolazine compared to other antianginal drugs 4
• Acute renal failure has been observed in some patients with severe renal impairment (creatinine clearance <30 mL/min) while taking ranolazine 1

In summary, while ranolazine can cause hypotension, it is an uncommon adverse effect. The drug's neutral hemodynamic profile makes it a potentially valuable option for patients with chronic stable angina who have bradycardia or hypotension, where other antianginal medications might worsen these conditions.