Long-Acting Oral Diltiazem Formulations
Long-acting oral diltiazem is available as extended-release (ER) or controlled-delivery (CD) formulations, dosed once daily at 120-540 mg, with slow-release preparations also available for divided dosing at 120-360 mg daily. 1
Available Formulations
Extended-Release/Controlled-Delivery (Once-Daily)
- Cardizem CD (controlled-delivery): Once-daily formulation designed for 24-hour controlled delivery, available in doses ranging from 120 mg to 540 mg daily 2, 3
- Standard dosing range: 120-360 mg once daily for most indications, with doses up to 540 mg/day studied and found safe for hypertension 1, 3, 4
- Minimum effective dose: 120 mg daily represents the starting dose for extended-release formulations 5, 2
- Therapeutic range: 180-420 mg once daily for hypertension and angina, with peak efficacy typically at 240-360 mg daily 2, 4
Slow-Release Formulations (Divided Dosing)
- Slow-release tablets: Available for divided dosing at 120-360 mg daily in 2-3 divided doses 1
- Onset of action: 2-4 hours with maintenance dosing 1
Key Pharmacokinetic Considerations
Nonlinear Pharmacokinetics
- Dose-dependent absorption: Diltiazem exhibits nonlinear disposition, with disproportionate increases in drug exposure at higher doses 6
- Therapeutic drug levels: Doses ≥240 mg/day provide trough blood levels within the therapeutic range (≥40 ng/mL) 4
- 24-hour efficacy: Extended-release formulations maintain consistent blood levels and blood pressure control throughout the dosing interval 3, 4
Chronotherapeutic Dosing
- Evening dosing advantage: Evening-dosed extended-release diltiazem provides greater morning blood pressure reduction, when cardiovascular events cluster, compared to morning dosing 3
- Circadian harmony: The long-acting formulation is designed with chronodynamics that align with diurnal blood pressure variation 3
Administration Guidelines
Formulation-Specific Instructions
- Extended-release capsules: Must be swallowed whole; cannot be split, crushed, or chewed 5, 2
- Immediate-release tablets (30-120 mg): May be swallowed whole, crushed, or chewed, but should not be split 7
Dose Titration
- Starting dose: 120-180 mg once daily for extended-release formulations 2, 4
- Titration interval: Increase gradually at 1-2 week intervals based on response 2, 4
- Maximum dose: 360-540 mg once daily, with 540 mg/day demonstrated as safe and well-tolerated 2, 3, 4
Clinical Efficacy Data
Transition from IV to Oral
- Conversion protocol: Oral long-acting diltiazem (180-360 mg/day) maintains heart rate control in 77% of patients when transitioning from IV diltiazem, with IV discontinued 4 hours after first oral dose 8
- Median effective dose: 300 mg/day of oral diltiazem CD for rate control in atrial fibrillation 8
Blood Pressure Control
- Dose-response relationship: Clear dose-dependent blood pressure reduction with doses ≥240 mg/day, with incremental benefit up to 540 mg/day 3, 4
- 24-hour coverage: Ambulatory blood pressure monitoring confirms consistent reductions throughout the dosing interval 4
Important Caveats
- Hepatic/renal impairment: No specific dosing data available; titrate with particular caution in these populations 7
- Drug interactions: Diltiazem is both a CYP3A4 substrate and moderate inhibitor, requiring caution with numerous medications including apixaban, cyclosporine, and statins 2
- Contraindications: Avoid in second/third-degree AV block without pacemaker, decompensated heart failure, severe LV dysfunction, and WPW syndrome with atrial fibrillation 1, 2
- Combination therapy caution: Use extreme caution when combining with beta-blockers due to risk of significant bradyarrhythmias and heart block 2