What is the recommended use and dosage of Diltiazem (a calcium channel blocker) for treating hypertension, angina, and arrhythmias?

Diltiazem: Recommended Use and Dosing

Diltiazem is recommended at 120-360 mg daily for hypertension and angina, with initial dosing at 120 mg daily (or 30 mg four times daily for immediate-release), titrated progressively over several weeks; for acute supraventricular tachycardia, use 0.25 mg/kg IV bolus (15-20 mg) over 2 minutes, though lower doses (≤0.2 mg/kg) may reduce hypotension risk while maintaining efficacy. 1, 2, 3, 4

Hypertension Management

Initial Dosing and Titration

• Start with 120-180 mg once daily using extended-release formulations (Cardizem CD or equivalent) 1
• Titrate cautiously and progressively over several weeks to achieve blood pressure control 1
• Maximum maintenance dose is 360 mg daily for most patients, though doses up to 420-540 mg have been studied safely 1
• For immediate-release formulations, start at 30 mg four times daily and increase gradually at 1-2 day intervals 3

Clinical Considerations

• Diltiazem may be particularly effective in low-renin hypertension, including elderly and Black populations 5
• Preferred over dihydropyridine calcium channel blockers in patients with baseline tachycardia, as it reduces heart rate at rest and during exercise 1
• Can be combined with ACE inhibitors/ARBs and thiazide diuretics if needed for blood pressure control 1
• If beta-blockers are contraindicated in patients with coronary artery disease, diltiazem may be substituted, but not if left ventricular dysfunction is present 1

Angina Pectoris

Dosing Strategy

• Typical maintenance dose is 240 mg daily, though the range is 120-360 mg daily 1
• For immediate-release: start 30 mg four times daily before meals and at bedtime, titrate at 1-2 day intervals 3
• Average optimum dosage range is 180-360 mg/day in divided doses 3
• Extended-release formulations allow once-daily dosing at 120-360 mg 1

Combination Therapy

• May be safely combined with short- and long-acting nitrates 3
• Sublingual nitroglycerin can be used as needed for acute anginal attacks during diltiazem therapy 3
• Exercise extreme caution when combining with beta-blockers due to increased risk of bradyarrhythmias and heart failure 1

Supraventricular Tachycardia (Acute Management)

IV Bolus Protocol

• Initial dose: 0.25 mg/kg (approximately 15-20 mg for average adult) IV over 2 minutes 2
• Alternative lower dose: ≤0.2 mg/kg may be equally effective with significantly reduced hypotension risk (adjusted OR 0.39 for hypotension vs standard dose) 4
• If initial bolus ineffective, may give second dose of 0.35 mg/kg over 2 minutes 6
• Adenosine remains first-line; diltiazem is an excellent second-line option if adenosine fails or is contraindicated 2

IV Infusion for Rate Control

• Continuous infusion: 5-15 mg/hour for sustained rate control 1
• Particularly useful in atrial flutter or atrial fibrillation with rapid ventricular response 6
• In adult congenital heart disease (ACHD) patients, use with extra caution and monitor closely for hypotension (occurs in up to 20% of patients) 6

Transition to Oral Therapy

• After successful conversion, transition to oral therapy at 120 mg daily (divided or single dose with long-acting formulations) 2
• Maximum daily oral dose for long-term management: 360 mg 2

Absolute Contraindications

Do not use diltiazem in the following situations: 1, 2

• Second or third-degree AV block without functioning ventricular pacemaker
• Sick sinus syndrome without pacemaker
• Wolff-Parkinson-White (WPW) syndrome with atrial fibrillation/flutter (risk of accelerated ventricular response)
• Decompensated systolic heart failure or severe left ventricular dysfunction
• Cardiogenic shock
• Severe hypotension

Relative Contraindications and Cautions

Use with Extreme Caution

• Hepatic dysfunction: diltiazem is metabolized by the liver; titrate carefully 1
• Renal dysfunction: may require dose adjustment 1
• Combination with beta-blockers: significantly increases risk of bradycardia, AV block, and heart failure; avoid routine combination 6, 1
• Medications with SA/AV nodal-blocking properties 1

Drug Interactions

• Diltiazem is both a CYP3A4 substrate (major) and moderate CYP3A4 inhibitor 1
• Use caution with: apixaban, itraconazole, bosutinib, ceritinib, cilostazol, cyclosporine, everolimus, ibrutinib, idelalisib, ivabradine, lomitapide, olaparib, ranolazine, rifampin, simeprevir 1

Adverse Effects and Monitoring

Common Adverse Effects

• Hypotension (most common, especially with IV administration; occurs in up to 20% with IV use) 6, 1, 2
• Peripheral edema (dose-related, more common in women; consider adding diuretics) 1
• Bradycardia (may be dose-limiting) 1, 2
• Constipation 1
• Headache and flushing 7

Serious Adverse Effects

• Worsening heart failure in patients with pre-existing ventricular dysfunction 1, 2
• Significant bradyarrhythmias, especially when combined with beta-blockers 1
• AV block (rare but serious) 8, 7
• Acute hepatic injury (rare) 1

Monitoring Requirements

• Blood pressure and heart rate regularly during dose titration and maintenance 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
• Reassess patients 1 month after initiation or dose change 1

Critical Safety Considerations

Emergency Preparedness

• Resuscitation equipment should always be available when administering IV diltiazem 2
• For severe bradycardia, consider atropine or temporary pacing 2
• Synchronized cardioversion is preferred over medication in hemodynamically unstable patients 6, 2

Special Populations

• Patients with single-ventricle physiology or systemic right ventricles may not tolerate ventricular rates >120 bpm for many hours 6
• Elderly patients may be at higher risk for AV block, especially with concomitant beta-blocker therapy 7
• Titration should be carried out with particular caution in patients with impaired renal or hepatic function 3