Oral Nicardipine for Hypertension and Angina
Primary Indication and FDA-Approved Use
Oral nicardipine is FDA-approved for chronic stable angina and hypertension, administered at 20-40 mg three times daily, and may be safely combined with beta-blockers, nitrates, and diuretics. 1
Dosing Regimen for Chronic Conditions
Angina Management
- Start at 20 mg three times daily and titrate based on response 1
- Effective doses range from 20-40 mg three times daily 1
- Allow at least 3 days between dose increases to achieve steady-state plasma concentrations 1
- May be safely combined with sublingual nitroglycerin for acute attacks, prophylactic nitrates, and beta-blockers 1
Hypertension Management
- Start at 20 mg three times daily and adjust according to blood pressure response 1
- Effective doses range from 20-40 mg three times daily 1
- Maximum blood pressure lowering occurs 1-2 hours after dosing, with prominent peak effects requiring blood pressure measurement at both peak (1-2 hours) and trough (8 hours) 1
- Allow at least 3 days between dose increases for steady-state achievement 1
- May be safely combined with thiazide diuretics and beta-blockers 1
Pharmacokinetic Profile Critical for Clinical Use
- Terminal half-life averages 8.6 hours at steady-state, though elimination over the first 8 hours is faster (2-4 hours half-life) 1
- Steady-state plasma levels achieved after 2-3 days of three-times-daily dosing and are two-fold higher than single-dose levels 1
- Highly protein-bound (>95%) in plasma 1
- Extensively metabolized by hepatic CYP2C8, 2D6, and 3A4; less than 1% excreted unchanged in urine 1
Special Population Dosing Adjustments
Renal Insufficiency
- Start at 20 mg three times daily with careful titration 1
- Plasma levels approximately two-fold higher in patients with mild renal impairment (creatinine 1.2-5.5 mg/dL) 1
Hepatic Insufficiency
- Start at 20 mg twice daily (note the reduced frequency) with individual titration 1
- In severe liver disease, Cmax and AUC are 1.8 and four-fold higher, with terminal half-life prolonged to 19 hours 1
Congestive Heart Failure
- Exercise caution when titrating; nicardipine has negative inotropic effects in patients with severe left ventricular dysfunction 1
Elderly Patients
- No dosage adjustment required; steady-state pharmacokinetics similar to young adults 1
Clinical Efficacy Evidence
Hypertension
- In 12 double-blind studies of mild-to-moderate hypertension, nicardipine lowered supine systolic blood pressure by 10-15 mm Hg and diastolic by 10 mm Hg 2
- Clear dose-response relationship exists from 10-40 mg three times daily 2
- In urgent hypertension (diastolic ≥120 mm Hg), oral nicardipine 30 mg achieved adequate blood pressure reduction in 65% of patients versus 22% with placebo 3
Angina
- In 9 double-blind crossover studies, nicardipine at 30-40 mg three times daily showed statistically significant improvement in exercise tolerance and time to onset of angina 2
- Equally effective as nifedipine for stable angina, with potential advantage of not depressing cardiac conduction or left ventricular function 4
- Remarkably effective in vasospastic angina in placebo-controlled studies 2
Important Drug Interactions
Nicardipine inhibits CYP3A4, CYP2D6, CYP2C8, and CYP2C19, which can significantly increase plasma levels of cyclosporine and tacrolimus, necessitating close monitoring and potential dose adjustment 1
Hemodynamic Effects and Cardiovascular Considerations
- Produces significant decrease in systemic vascular resistance, more prominent in hypertensive patients 1
- Mean heart rate typically increases by 5-10 beats per minute at peak plasma levels, with greater increases at higher doses 1
- Increases ejection fraction and cardiac output with no significant change or small decrease in left ventricular end-diastolic pressure 1
- No detrimental effects on cardiac conduction system at therapeutic doses 1
- Improves left ventricular diastolic distensibility during early filling phase 1
Common Adverse Effects
The most common side effects are flushing, palpitations, headache, and pedal edema, attributed to vasodilatory properties 2
- These effects are dose-related and more frequent within the first few weeks of therapy 4
- Most effects are minor and transient 4
- In clinical trials with over 2,000 patients, no deaths or serious adverse reactions were attributed to nicardipine 2
Critical Clinical Context: Oral vs. Intravenous Use
Oral nicardipine is NOT appropriate for hypertensive emergencies or urgent blood pressure reduction in the emergency department setting. 5, 6
- For hypertensive urgency (severe BP elevation without target organ damage), first-line oral agents are captopril, labetalol, or extended-release nifedipine, not nicardipine 5, 6
- Intravenous nicardipine is reserved for hypertensive emergencies with acute target organ damage, requiring ICU-level monitoring 5, 7, 6
Transition from IV to Oral Nicardipine
For patients initially controlled with IV nicardipine who require transition to oral therapy:
- Begin oral nicardipine 40 mg at 1 hour prior to discontinuation of IV infusion 8
- Continue 40 mg three times daily initially, then downtitrate as needed 8
- In a study of 21 patients with severe hypertension, mean systolic blood pressure was lowered by 50 mm Hg at end of oral treatment compared to baseline 8
- At end of oral treatment, 6 patients remained on nicardipine monotherapy, 8 required two-drug therapy, and 7 required three-drug therapy 8
Long-Term Management Considerations
Oral nicardipine provides effective long-term control of hypertension and angina, though many patients with severe hypertension eventually require additional antihypertensive therapy. 8