Diltiazem CD Dosing and Management
For hypertension, Diltiazem CD should be initiated at 180-240 mg once daily and titrated up to 360-480 mg daily for optimal blood pressure control, while angina typically requires lower doses of 180-240 mg daily. 1, 2
Dosing Guidelines
Hypertension
- Start at 180-240 mg once daily and titrate upward based on blood pressure response 1
- Target maintenance dose: 360-480 mg once daily for most patients with hypertension 1, 2
- Doses up to 540 mg/day have been studied and found safe, with clear linear dose-response relationship through this range 2, 3
- Critical point: Hypertension is commonly underdosed - the 90-120 mg/day range is essentially a "no-effect dose" for blood pressure control 2
- Titrate cautiously and progressively over several weeks to reach effective control 1
Angina Pectoris
- Start at 120-180 mg once daily for the extended-release formulation 1
- Typical maintenance dose: 180-240 mg daily for angina control 1, 2, 4
- Maximum dose: 360 mg daily may be required in some patients 5, 6
- For immediate-release formulation: Start 30 mg four times daily, titrate gradually at 1-2 day intervals to 180-360 mg/day in divided doses 5
Combination Therapy Considerations
- When beta-blockers are contraindicated or cause intolerable side effects, diltiazem may be substituted as monotherapy, but NOT if left ventricular dysfunction is present 7
- If angina or hypertension remains uncontrolled on beta-blocker, ACE inhibitor, and thiazide, a long-acting dihydropyridine CCB can be added rather than diltiazem 7
- Extreme caution required when combining diltiazem with beta-blockers due to increased risk of significant bradyarrhythmias and heart failure 7, 1
Absolute Contraindications
Do not use diltiazem in patients with: 1
- Second- or third-degree AV block without a functioning pacemaker 1
- Sick sinus syndrome without a pacemaker 1
- Decompensated systolic heart failure or severe left ventricular dysfunction 7, 1
- Cardiogenic shock 1
- Wolff-Parkinson-White syndrome with atrial fibrillation/flutter 1
- Hypotension 1
Relative Contraindications and Cautions
- Avoid routine combination with beta-blockers - reserve for refractory cases only with close monitoring 7, 1
- Use caution in patients with PR interval >0.24 seconds 1
- Use caution in hepatic dysfunction (diltiazem is hepatically metabolized) 1
- Dose adjustment may be required in renal dysfunction 1
- Critical drug interactions: Diltiazem is a CYP3A4 substrate and moderate inhibitor - use caution with apixaban, itraconazole, bosutinib, ceritinib, cilostazol, cyclosporine, everolimus, and other CYP3A4 substrates 1
Monitoring Requirements
Essential monitoring parameters: 1
- Blood pressure and heart rate at each visit
- Signs and symptoms of heart failure in at-risk patients
- ECG monitoring in patients with conduction system disease
- Liver function tests if clinically indicated
- Reassess patients 1 month after initiation or dose change 1
Common Adverse Effects
- Peripheral edema (dose-related, more common in women) - consider adding diuretics 1
- Hypotension (most common adverse effect) 1
- Bradycardia (may be dose-limiting) 1
- Constipation 1
- Worsening heart failure in patients with pre-existing ventricular dysfunction 1
- Abnormal liver function tests and acute hepatic injury (rare) 1
Clinical Pearls
- Diltiazem is generally underdosed for hypertension - historical prescribing patterns favor 180-240 mg doses that were established for angina, but hypertension typically requires 360-480 mg daily 2
- Preferred over dihydropyridines in patients with baseline tachycardia, as it reduces heart rate at rest and during exercise 1
- Can be safely coadministered with short- and long-acting nitrates for angina 5
- The once-daily CD formulation maintains consistent blood levels over 24 hours 1
- Nonlinear pharmacokinetics - apparent oral clearance decreases 35-51% over dose escalation, meaning higher doses produce disproportionately greater drug exposure 3