What is the recommended dosage and usage of extended release diltiazem (calcium channel blocker) for patients with hypertension or angina?

Extended Release Diltiazem: Dosing and Management

Recommended Dosing

For hypertension, start extended-release diltiazem at 120-180 mg once daily and titrate up to 240-360 mg daily, with doses up to 540 mg/day proven safe and effective for blood pressure control. 1, 2, 3

Initial Dosing Strategy

• Start at 120 mg once daily for most patients with hypertension or angina 1
• For hypertension specifically, the 120 mg dose is essentially a "no-effect dose" and should be viewed as a starting point only 4
• Titrate cautiously over several weeks to reach effective blood pressure control 1

Target Maintenance Doses

• Hypertension: 240-360 mg once daily is the typical effective range, though doses up to 540 mg/day have demonstrated clear dose-response benefits 1, 2, 4
• Angina: 240 mg once daily is typically sufficient 1, 4
• The dose-response relationship for blood pressure lowering is linear through the 480-540 mg/day range 4

Critical Dosing Insight

Diltiazem is commonly underdosed for hypertension—physicians frequently prescribe 180-240 mg doses when 360 mg or higher is often needed for optimal blood pressure control. 4 This underdosing stems from historical use at lower antianginal doses before hypertension approval 4.

Absolute Contraindications

Do not use diltiazem in the following situations: 1, 5

• Second- or third-degree AV block without a functioning pacemaker 1, 5
• Sick sinus syndrome without a pacemaker 1, 5
• Decompensated systolic heart failure or severe left ventricular dysfunction 1, 5
• Cardiogenic shock 1, 5
• Wolff-Parkinson-White syndrome with atrial fibrillation/flutter 1
• Hypotension (systolic <130 mmHg or diastolic <80 mmHg as a reasonable threshold) 6, 1

Relative Contraindications and Cautions

Combination with Beta-Blockers

Exercise extreme caution when combining diltiazem with beta-blockers due to increased risk of significant bradyarrhythmias and heart failure. 6, 1 This combination should generally be avoided unless absolutely necessary 1. If used together, close monitoring for excessive bradycardia and heart block is mandatory 1.

Left Ventricular Dysfunction

• Verapamil and diltiazem should be avoided in patients with pulmonary edema or evidence of severe LV dysfunction 6
• Retrospective analyses suggest detrimental mortality effects in patients with LV dysfunction 6
• For hypertension with stable angina, if beta-blockers are contraindicated, diltiazem may substitute but NOT if LV dysfunction is present 1

Conduction System Disease

• Use with caution in patients with PR interval >0.24 seconds 1
• Avoid in patients with first-degree AV block if combined with other AV nodal blocking agents 1
• Diltiazem prolongs AV node refractory periods and may rarely result in abnormally slow heart rates 5

Drug Interactions

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

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

Hepatic and Renal Dysfunction

• Use with caution in hepatic dysfunction as diltiazem is metabolized by the liver 1
• May require dose adjustment in renal dysfunction 1
• Rare instances of acute hepatic injury with elevated liver enzymes have been noted 5

Clinical Indications and Evidence Base

Unstable Angina/NSTEMI

Diltiazem may be used to control ongoing or recurring ischemia-related symptoms in patients already receiving adequate doses of nitrates and beta-blockers, or when these agents cannot be tolerated. 6

• The Diltiazem Reinfarction Study showed diltiazem reduced reinfarction and refractory angina at 14 days without increasing mortality 6
• The evidence base in UA/NSTEMI is greatest for verapamil and diltiazem compared to other calcium channel blockers 6
• Definitive evidence for benefit is predominantly limited to symptom control 6

Hypertension with Coronary Disease

• Long-acting dihydropyridine agents are preferred over nondihydropyridines (diltiazem/verapamil) for combination with beta-blockers to avoid excessive bradycardia 6
• The INVEST trial showed no difference between verapamil and atenolol in cardiovascular outcomes in 22,000 hypertensive patients with chronic CAD 6
• Diltiazem can be combined with ACE inhibitor/ARB and thiazide diuretic if needed for BP control 1

Monitoring Requirements

Monitor the following parameters regularly: 1

• Blood pressure and heart rate at each visit 1
• Signs and symptoms of heart failure in at-risk patients 1
• Liver function tests if clinically indicated 1
• ECG monitoring in patients with conduction system disease 1
• Reassess patients 1 month after initiation or dose change 1

Common Adverse Effects

Most Frequent Side Effects

• Hypotension is the most common adverse effect 1, 5
• Peripheral edema is dose-related, more common in women; consider adding diuretics 1
• Bradycardia, particularly when combined with beta-blockers 1, 5
• Constipation 1
• Dizziness and flushing 1

Serious Adverse Effects

• Worsening heart failure in patients with pre-existing ventricular dysfunction 1, 5
• Significant bradyarrhythmias, especially with beta-blocker combination 1
• Abnormal liver function tests and acute hepatic injury (rare) 1, 5
• AV block 1, 5

Special Populations and Clinical Pearls

Patients with Tachycardia

Diltiazem is preferred over dihydropyridines (like nifedipine) in patients with baseline tachycardia. 6, 1 Diltiazem has a genuine heart rate-regulating effect: it reduces tachycardia without inducing excessive bradycardia 7. The heart rate-lowering effect is proportional to baseline heart rate, with significant effects when baseline HR is ≥74 beats/min 7.

Elderly Patients

• Diltiazem is effective and well-tolerated in elderly patients (65-85 years) with mild-to-moderate hypertension 1
• Elderly or frail patients may be more susceptible to symptomatic hypotension even at higher BP readings 1

Low Blood Pressure Management

• Asymptomatic low blood pressure (e.g., 115/60 mmHg) does not usually require therapy change 1
• Assess for dizziness, lightheadedness when standing, confusion, or altered mental status before dosing 1
• For atrial fibrillation rate control, heart rate is more important than blood pressure 1

Formulation Considerations

• Extended-release formulations (Cardizem CD, Dilacor XR) provide controlled delivery over 24 hours 1, 3
• Trough drug blood levels ≥40 ng/mL are within therapeutic range, achieved with doses ≥240 mg/day 2
• The extended-release formulation shows consistent blood pressure reduction throughout the 24-hour dosing interval 2, 3

Key Pitfalls to Avoid

1. Underdosing for hypertension: The 180-240 mg doses constitute >70% of prescriptions but are often inadequate 4
2. Combining with beta-blockers without careful monitoring: This significantly increases risk of bradycardia and heart block 6, 1
3. Using in patients with LV dysfunction: Can worsen heart failure and increase mortality 6, 1
4. Rapid dose escalation: Titrate cautiously over several weeks 1
5. Ignoring drug interactions: Remember CYP3A4 interactions 1