What is the recommended dose of Diltiazem (Calcium Channel Blocker) for treating hypertension and angina?

Diltiazem Dosing for Hypertension and Angina

For hypertension, start diltiazem at 120-180 mg once daily (extended-release formulation) and titrate up to 360 mg daily, while for angina, the typical effective dose is 180-240 mg daily in divided doses or as extended-release, with immediate-release formulations starting at 30 mg four times daily. 1, 2

Hypertension Dosing

The optimal dose for hypertension is typically 360 mg daily, which is higher than what most physicians prescribe but is supported by dose-response data showing linear blood pressure reduction through 480-540 mg/day. 3

Initial Dosing Strategy

• Start with 120-180 mg once daily using extended-release formulations 1
• The 180 mg once-daily dose controls hypertension in approximately 62.5% of patients with mild-to-moderate hypertension 4
• Titrate cautiously and progressively over several weeks to reach effective blood pressure control 1

Maintenance Dosing

• Target dose range: 240-360 mg daily for most patients with hypertension 1, 3
• Maximum dose studied safely: 480-540 mg/day, though 360 mg is the typical maximum recommended 1, 3
• Extended-release formulations allow once-daily dosing at 120-540 mg 1
• Research demonstrates that 90-120 mg/day is essentially a "no-effect dose" for hypertension 3

Common Pitfall

Most physicians underdose diltiazem for hypertension, prescribing 180-240 mg when 360 mg is often needed for optimal blood pressure control. 3 This occurs because physicians became accustomed to lower antianginal doses (240 mg) before the hypertension indication was approved, and early extended-release formulations were limited to 240-300 mg capsule strengths due to bulk constraints 3.

Angina Dosing

Immediate-Release Formulation

• Start at 30 mg four times daily (before meals and at bedtime) 2
• Increase gradually at 1-2 day intervals in divided doses (3-4 times daily) 2
• Optimal dosage range: 180-360 mg/day in divided doses 2
• Average effective dose: 240 mg/day 3, 5

Extended-Release Formulation

• Start at 120-180 mg once daily 1
• Typical maintenance: 240 mg once daily 3
• Maximum: 360 mg once daily if needed 1

Combination Therapy

• Diltiazem can be safely combined with sublingual nitroglycerin for acute anginal attacks 2
• May be coadministered with short- and long-acting nitrates, though controlled efficacy data for this combination are limited 2
• Exercise caution when combining with beta-blockers due to risk of significant bradyarrhythmias and heart failure 6, 1

Absolute Contraindications

Do not use diltiazem in the following situations: 6, 1

• Second- or third-degree AV block without a functioning pacemaker 6, 1
• Sick sinus syndrome without a pacemaker 1, 7
• Decompensated systolic heart failure or severe left ventricular dysfunction 6, 1
• Cardiogenic shock 1
• Wolff-Parkinson-White syndrome with atrial fibrillation/flutter 1, 7
• Hypotension 1, 7

Relative Contraindications and Cautions

• Avoid routine combination with beta-blockers due to increased risk of bradycardia and heart block 1, 7
• Use with caution in hepatic dysfunction (diltiazem is metabolized by the liver) 1
• Use with caution in renal dysfunction (may require dose adjustment) 1, 2
• PR interval >0.24 seconds 6

Drug Interactions

Diltiazem is both a CYP3A4 substrate (major) and a moderate CYP3A4 inhibitor. 1 Exercise caution with:

• Apixaban, itraconazole, bosutinib, ceritinib, cilostazol 1
• Cyclosporine, everolimus, ibrutinib, idelalisib 1
• Ivabradine, lomitapide, olaparib, ranolazine 1
• Rifampin, simeprevir 1

Monitoring Requirements

Monitor the following parameters: 1

• Blood pressure and heart rate regularly during dose titration 1
• Signs and symptoms of heart failure in at-risk patients 1
• ECG monitoring in patients with conduction system disease 1
• Liver function tests if clinically indicated 1

Common Adverse Effects

• Hypotension (most common) 1, 7
• Peripheral edema (dose-related, more common in women; consider adding diuretics) 1, 5
• Bradycardia 1, 7
• Constipation 1
• Worsening heart failure in patients with pre-existing ventricular dysfunction 1, 7
• Abnormal liver function tests and acute hepatic injury (rare) 1

Special Clinical Situations

Patients with Tachycardia

• Diltiazem is preferred over dihydropyridines (nifedipine, amlodipine) in patients with baseline tachycardia 6, 1

Elderly Patients

• Sustained-release diltiazem 200-300 mg once daily is effective and well-tolerated in elderly patients (65-85 years) with mild-to-moderate hypertension 8
• Start at 200 mg as the recommended starting dose in elderly patients 8

Non-ST-Elevation Acute Coronary Syndromes

• Use diltiazem for continuing or recurrent ischemia when beta-blockers are contraindicated, not successful, or cause unacceptable side effects 6
• Do not use in patients with clinically significant LV dysfunction, increased risk for cardiogenic shock, PR interval >0.24 seconds, or second/third-degree AV block without a pacemaker 6