What is the recommended dosage and use of Diltiazem (a calcium channel blocker) in clinical scenarios?

Diltiazem: Dosing and Clinical Use

Oral Formulations for Chronic Management

For hypertension and angina, initiate diltiazem at 120 mg daily and titrate cautiously over several weeks to a maximum of 360 mg daily, monitoring blood pressure and heart rate at each adjustment. 1

Standard Dosing Ranges

• Initial dose: 120 mg daily (divided doses or single dose with long-acting formulations) 1
• Maintenance range: 120-360 mg daily 1
• Hypertension: Often requires higher doses (up to 360 mg daily) 1
• Angina: Typically 240 mg daily 1
• Extended-release (ER) or controlled-delivery (CD) formulations allow once-daily dosing at 120-540 mg, though standard range is 120-360 mg 1

Available Formulations

• Immediate-release tablets: 30-90 mg 1
• Extended-release once-daily (Cardizem CD): 180-420 mg for hypertension and angina 1
• Slow-release tablets: 120-360 mg daily in 2-3 divided doses 1

Intravenous Administration for Acute Rate Control

For atrial fibrillation/flutter with rapid ventricular response or PSVT, administer 0.25 mg/kg (approximately 15-20 mg for average adult) IV over 2 minutes, with a second dose of 0.35 mg/kg (approximately 25 mg) after 15 minutes if inadequate response. 2, 3

IV Bolus Protocol

• First dose: 0.25 mg/kg actual body weight over 2 minutes (20 mg reasonable for average patient) 2, 3
• Second dose (if needed after 15 minutes): 0.35 mg/kg over 2 minutes (25 mg reasonable for average patient) 2, 3
• Some patients may respond to initial dose of 0.15 mg/kg, though duration of action may be shorter 3
• Lower doses (≤10 mg) are commonly used in practice but less effective: Dosing ≥0.13 mg/kg achieves heart rate <100 bpm in mean 169 minutes vs 318 minutes with <0.13 mg/kg 4

Continuous IV Infusion

• Initial rate: 10 mg/hour (some patients maintain response at 5 mg/hour) 3
• Titration: Increase in 5 mg/hour increments up to 15 mg/hour as needed 3
• Maximum duration: 24 hours (longer durations and rates >15 mg/hour not studied) 3
• Median effective infusion rate is 10 mg/hour 5

Transition from IV to Oral

• Administer oral long-acting diltiazem (180-360 mg daily) while maintaining stable heart rate control on constant infusion 5
• Discontinue IV infusion 4 hours after first oral dose 5
• 77% of patients maintain heart rate control during transition, with median oral dose of 300 mg/day 5

Absolute Contraindications

Never use diltiazem in the following scenarios: 1, 2, 6

• Second or third-degree AV block without functioning ventricular pacemaker 1, 2, 6
• Sick sinus syndrome without pacemaker 1, 2
• Wolff-Parkinson-White (WPW) syndrome with atrial fibrillation/flutter 1, 2, 6
• Decompensated systolic heart failure or severe LV dysfunction 1, 2, 6
• Cardiogenic shock 1, 6
• Hypotension 2

Critical Precautions and Relative Contraindications

Combination with Beta-Blockers

Avoid routine combination of diltiazem with beta-blockers due to increased risk of significant bradyarrhythmias and heart failure; if combined, monitor extremely closely. 1, 6

Conduction System Disease

• Use caution with PR interval >0.24 seconds 1
• Avoid in first-degree AV block if considering combination with beta-blockers 1
• ECG monitoring required in patients with conduction system disease 1

Heart Failure Considerations

• Diltiazem is 95-97% effective for rate control even in moderate-to-severe heart failure (NYHA class III-IV, EF 36%) 7
• However, use with extreme caution due to negative inotropic effects 6, 7
• Monitor closely for worsening heart failure symptoms (increased dyspnea, weight gain, edema) 1, 6

Hepatic and Renal Dysfunction

• Use caution in hepatic dysfunction (diltiazem is metabolized by liver) 1
• May require dose adjustment in renal dysfunction 1

Drug Interactions

Diltiazem is both a CYP3A4 substrate (major) and moderate CYP3A4 inhibitor. 1, 6

Use caution with: 1, 6

• Apixaban
• Itraconazole
• Bosutinib
• Ceritinib
• Cilostazol
• Cyclosporine
• Everolimus
• Ibrutinib
• Idelalisib
• Ivabradine
• Lomitapide
• Olaparib
• Ranolazine
• Rifampin
• Simeprevir

Adverse Effects and Monitoring

Common Adverse Effects

• Hypotension (most common, dose-related) 1, 2, 6
• Peripheral edema (dose-related, more common in women; consider adding diuretics) 1
• Bradycardia 1, 2, 6
• Constipation 1
• Worsening heart failure in predisposed patients 1, 2, 6
• Abnormal liver function tests and acute hepatic injury 1, 6

Monitoring Requirements

• Blood pressure and heart rate at each visit during titration 1, 6
• Signs and symptoms of heart failure in at-risk patients 1, 6
• ECG monitoring in patients with conduction system disease 1, 6
• Liver function tests if clinically indicated 1, 6

Management of Hypotension

Asymptomatic low blood pressure (e.g., 115/60 mmHg) does not require medication adjustment. 1

• Assess for dizziness, lightheadedness when standing, confusion, or altered mental status before each dose 1
• Symptomatic hypotension may require dose adjustment or reconsideration of other vasodilators 1
• For severe bradycardia, consider atropine or temporary pacing 2

Special Clinical Scenarios

Paroxysmal Supraventricular Tachycardia (PSVT)

• Adenosine is first-line; diltiazem is excellent second-line option if adenosine fails or is contraindicated 2
• Diltiazem works by slowing AV node conduction and increasing AV node refractoriness 2
• Synchronized cardioversion preferred in hemodynamically unstable patients 2
• Resuscitation equipment should always be available when administering IV diltiazem 2

Diastolic Dysfunction

• Diltiazem improves diastolic dysfunction through negative inotropic effects, heart rate reduction (prolonging diastolic filling period), and direct improvement in diastolic performance 6
• Reasonable second-line option when beta-blockers not tolerated or ineffective 6
• Critical warning: Use cautiously in severe outflow tract obstruction, elevated pulmonary artery wedge pressure, and low systemic blood pressure—decrease in BP may trigger increased outflow obstruction and precipitate pulmonary edema 6
• Avoid in obstructive physiology (vasodilatory effects may aggravate outflow obstruction) 6

Hypertension with Coronary Artery Disease

• If beta-blockers contraindicated, diltiazem may be substituted, but not if LV dysfunction present 1
• Can be combined with ACE inhibitor/ARB and thiazide diuretic if needed for BP control 1

Patients with Baseline Tachycardia

• Diltiazem preferred over dihydropyridines in patients with relative tachycardia 1
• Reduces heart rate at rest and during exercise 1

Elderly Patients

• Effective and well-tolerated in elderly patients (65-85 years) with mild-to-moderate hypertension 8
• More susceptible to symptomatic hypotension even at higher BP readings—symptom assessment particularly important 1

Clinical Pearls

• Low-dose diltiazem (≤0.2 mg/kg) may be as effective as standard dose (>0.2-0.3 mg/kg) for rapid AF with lower hypotension risk (18% vs 35%) 9
• However, weight-based dosing ≥0.13 mg/kg achieves significantly faster rate control than lower doses 4
• Onset of action for slow-release tablets is 2-4 hours with maintenance dosing 1
• Reassess patients 1 month after initiation or dose change, monitoring for return of symptoms (elevated BP, angina, rapid heart rate) 1