Latest FDA-Approved Calcium Channel Blockers
The most recently FDA-approved calcium channel blocker is clevidipine (Cleviprex), which received initial U.S. approval in 2008 1. This represents the newest calcium channel blocker available in the United States.
Clevidipine: The Latest Addition
Clevidipine is an ultrashort-acting intravenous dihydropyridine calcium channel blocker specifically indicated for acute blood pressure reduction when oral therapy is not feasible or desirable 1, 2.
Key Distinguishing Features
- Ultra-rapid onset and offset: Half-life of approximately 1-2 minutes, allowing precise titration 1, 3, 4
- Unique metabolism: Metabolized by blood and tissue esterases (not hepatic or renal), preventing drug accumulation even in organ dysfunction 3, 4
- Vascular selectivity: Acts on arterial smooth muscle without venous effects 3
- Formulation: Available as 0.5 mg/mL injectable emulsion in 50 mL or 100 mL single-use vials 1
Clinical Dosing
- Initial dose: 1-2 mg/hour IV infusion 1
- Titration: Double dose at 90-second intervals initially; as blood pressure approaches goal, increase by less than doubling every 5-10 minutes 1
- Maintenance: Most patients respond at 4-6 mg/hour 1
- Maximum: Up to 16 mg/hour for most patients (limited experience up to 32 mg/hour); maximum 1000 mL or 21 mg/hour average per 24 hours due to lipid load 1
Critical Safety Considerations
Clevidipine is contraindicated in patients with soy or egg allergy, defective lipid metabolism, or severe aortic stenosis 1. The drug must be handled with strict aseptic technique and discarded 12 hours after stopper puncture 1. Monitor for rebound hypertension for at least 8 hours after discontinuation in patients not transitioned to oral therapy 1, 3.
Currently Available Calcium Channel Blockers
Beyond clevidipine, the established calcium channel blockers remain in widespread use:
Dihydropyridines
- Amlodipine: Long-acting oral agent with gradual onset/offset (pKa=8.6), providing 24-hour blood pressure control 5
- Nifedipine: Available in immediate and extended-release formulations; rapid-release short-acting nifedipine must be avoided without concomitant beta-blockade due to increased adverse outcomes 6
- Felodipine: Well-tolerated in mild left ventricular dysfunction 6
Non-Dihydropyridines
- Verapamil: Prominent AV nodal and sinus node effects with peripheral vasodilation 6
- Diltiazem: Similar to verapamil with balanced cardiac and vascular effects 6
Guideline-Recommended Use
Dihydropyridine calcium channel blockers are recommended as first-line therapy for hypertension in diabetes, alongside ACE inhibitors, ARBs, and thiazide-like diuretics 6. They demonstrate equivalent cardiovascular event reduction compared to other first-line agents in patients without albuminuria 6.
Clinical Context
In acute coronary syndromes, calcium channel blockers control ongoing ischemia in patients already receiving nitrates and beta-blockers, or when these agents are not tolerated 6. Verapamil and diltiazem should be avoided in patients with pulmonary edema or severe left ventricular dysfunction 6.