What is the difference between amlodipine (calcium channel blocker) and felodipine (calcium channel blocker) in treating a patient with hypertension and no significant comorbidities?

Amlodipine vs Felodipine for Hypertension

Both amlodipine and felodipine are second-generation dihydropyridine calcium channel blockers that effectively lower blood pressure in hypertensive patients, but amlodipine demonstrates superior 24-hour blood pressure control, particularly during nighttime hours, and is more potent on a milligram-to-milligram basis with fewer side effects. 1, 2

Pharmacological Differences

Duration of Action and Potency

• Amlodipine has a significantly longer elimination half-life than felodipine, which translates to more consistent blood pressure control throughout the 24-hour dosing interval 1
• Amlodipine is more potent milligram-for-milligram, requiring lower average daily doses (7.4 mg) compared to felodipine (11.2 mg) to achieve similar blood pressure reductions 2
• Both agents are longer-acting dihydropyridines with greater selectivity for vascular smooth muscle calcium channels over myocardial channels, distinguishing them from first-generation agents 3, 4

Blood Pressure Control Patterns

• Nighttime blood pressure control is significantly better with amlodipine (systolic P=0.026, diastolic P=0.019) compared to felodipine extended-release 1
• Daytime ambulatory blood pressure control (07:00-23:00) is comparable between both agents 1
• Amlodipine achieves target blood pressure in more patients: 82% vs 69% at 8 weeks (P=0.036) and 50% vs 33% at 4 weeks (P=0.013) 1
• The 24-hour systolic blood pressure reduction is significantly greater with amlodipine (P<0.001), though diastolic reductions are similar 2

Side Effect Profile

Tolerability Differences

• Felodipine causes significantly more headache and flushing (P<0.05) compared to amlodipine 2
• Both agents show similar withdrawal rates due to adverse effects (approximately 6% in comparative trials) 2
• Peripheral edema, hypotension, and reflex tachycardia remain potential side effects for both agents as dihydropyridines 3

Clinical Context and Safety

Use in Specific Populations

• Both amlodipine and felodipine are reasonably well tolerated in patients with mild left ventricular dysfunction, though neither has been studied in unstable angina/NSTEMI settings 3
• In heart failure with reduced ejection fraction, neither agent provides survival benefit, though amlodipine demonstrated neutral effects on morbidity and mortality in large trials and may be used for managing concurrent hypertension or ischemic heart disease 3
• Avoid both agents in patients with pulmonary edema or severe left ventricular dysfunction—this recommendation applies to all dihydropyridines 3

Cardiovascular Outcomes

• Both agents reduce cardiovascular morbidity and mortality associated with hypertension, including stroke prevention 5
• Calcium channel blockers as a class appear less effective than ACE inhibitors and diuretics for preventing heart failure and myocardial infarction 5
• Neither amlodipine nor felodipine shows superiority over the other for hard cardiovascular endpoints in head-to-head trials 3

Practical Prescribing Considerations

Dosing and Administration

• Amlodipine starting dose: 5 mg once daily, may increase to 10 mg if target blood pressure not achieved 1
• Felodipine ER starting dose: 5 mg once daily, may titrate to 10-20 mg as needed 1, 2
• Both agents provide true once-daily dosing with consistent trough-to-peak ratios 4

When to Choose Each Agent

• Choose amlodipine when: Nighttime blood pressure control is a priority, patient compliance may be enhanced by fewer side effects, or when using lower doses is preferred 1, 2
• Choose felodipine when: Amlodipine is not available or not tolerated, though recognize it may require higher doses and cause more vasodilatory side effects 2

Important Caveats

• Never use rapid-release, short-acting dihydropyridines (like immediate-release nifedipine) without concurrent beta-blockade due to increased adverse potential and mortality risk 3
• Both agents have similar coronary dilatory properties and peripheral arterial vasodilatory effects with minimal AV node or sinus node effects 3
• The longer half-life of amlodipine provides more forgiveness for missed doses and reduces blood pressure variability 6, 1