Cilnidipine Side Effects
Cilnidipine is generally well-tolerated with a favorable side effect profile compared to other calcium channel blockers, particularly causing less pedal edema and reflex tachycardia than amlodipine due to its dual L/N-type calcium channel blocking activity. 1, 2
Common Side Effects
Vasodilatory Effects
- Headache is a common side effect of dihydropyridine calcium channel blockers including cilnidipine, occurring due to peripheral arterial and cerebral vasodilation 3
- Headaches typically occur during initial treatment or dose increases and may diminish over time as tolerance develops 3
- Hypotension can occur, particularly during dose titration, though cilnidipine's N-type calcium channel blockade helps mitigate excessive blood pressure drops 4
Peripheral Edema
- Pedal edema occurs less frequently with cilnidipine compared to L-type-only calcium channel blockers like amlodipine, due to its dual L/N-type calcium channel blocking activity 1, 2
- This represents a significant clinical advantage, as peripheral edema is one of the most common reasons for discontinuation of dihydropyridine calcium channel blockers 5
Cardiovascular Effects
- Cilnidipine causes less reflex tachycardia compared to other dihydropyridine calcium channel blockers due to its N-type calcium channel blockade, which inhibits sympathetic nervous system activation 2, 6
- In the ACHIEVE-ONE trial, cilnidipine actually reduced pulse rate by 1.3 to 3.2 beats per minute depending on baseline values, rather than increasing it 6
Serious but Rare Side Effects
Severe Hypotension
- In high-dose calcium channel blocker testing, some patients developed systemic hypotension requiring discontinuation 4
- Three patients in one study were unable to tolerate more than a single dose due to systemic hypotension, with maximal hypotensive effects occurring within the first 60 minutes 4
- The hypotension was associated with increased right atrial pressure and decreased cardiac output, suggesting direct negative inotropic effects 4
Gastrointestinal Effects
- At higher doses, nausea and vomiting have been reported, though these side effects were transient and dose-related 4
- Dyspnea was reported in patients unable to tolerate upward titration of calcium channel blockers 4
Important Clinical Considerations
Contraindications and Cautions
- Avoid in patients with severe left ventricular dysfunction or pulmonary edema, as calcium channel blockers do not improve survival and may worsen outcomes in heart failure with reduced ejection fraction 4, 5
- Do not use short-acting formulations without concomitant beta-blocker therapy in patients with coronary artery disease due to increased adverse potential 5, 3
- May worsen symptoms in patients with erythromelalgia; discontinuation has resulted in symptom resolution in several cases 5
Advantages Over Other Calcium Channel Blockers
- Better tolerability profile with less pedal edema compared to amlodipine 1, 2
- No reflex tachycardia due to sympathetic nervous system inhibition via N-type calcium channel blockade 2, 6
- Better control of proteinuria in patients with chronic kidney disease compared to L-type-only calcium channel blockers 2, 7
Management of Side Effects
If Headaches Occur
- Consider reducing the dose of cilnidipine 3
- Switch to a longer-acting formulation if available 3
- Consider changing to a different calcium channel blocker or adding a beta-blocker 3