What is the typical dosing regimen for diltiazem (calcium channel blocker) in the management of atrial fibrillation (Afib)?

Diltiazem Dosing for Atrial Fibrillation Rate Control

For acute rate control in atrial fibrillation, administer diltiazem 0.25 mg/kg IV bolus over 2 minutes, followed by a continuous infusion of 5-15 mg/hour; for chronic oral maintenance, use 120-360 mg daily of extended-release formulation. 1

Acute Intravenous Dosing

Initial Bolus

• Administer 0.25 mg/kg IV over 2 minutes as the initial bolus dose 1, 2
• A second bolus of 0.35 mg/kg may be given 15 minutes later if inadequate response 2
• Onset of action occurs within 2-7 minutes after IV administration 2

Continuous Infusion

• Start infusion at 5-15 mg/hour immediately after bolus 1, 2
• Titrate in 5 mg/hour increments up to 15 mg/hour maximum based on heart rate response 1, 2
• Maintain infusion until heart rate control achieved (target <100 bpm) 1

Evidence-Based Dosing Considerations

The guideline-recommended 0.25 mg/kg dose carries a Class I recommendation with Level of Evidence B, making it the most strongly supported regimen 1, 2. However, recent research suggests important nuances:

• Weight-based dosing ≥0.13 mg/kg achieves rate control significantly faster (169 minutes vs 318 minutes) compared to lower doses 3
• Despite concerns, doses ≥0.13 mg/kg do not increase hypotension or bradycardia risk 3
• Lower doses (≤0.2 mg/kg) may be equally effective for rate control while reducing hypotension risk (18% vs 35% with standard dosing) 4

Clinical Pearl: While guidelines recommend 0.25 mg/kg, starting with 0.2 mg/kg (approximately 15-20 mg for average adults) balances efficacy with safety, particularly in elderly patients or those with borderline blood pressure 4.

Oral Maintenance Dosing

Extended-Release Formulations (Preferred)

• Start with 120-360 mg once daily 1
• Most patients require 240-360 mg daily for adequate rate control 1
• Half-life of extended-release formulations is 4-9.5 hours 2

Immediate-Release Formulations

• Administer 120-360 mg daily in divided doses (typically 60 mg three times daily up to 120 mg three times daily) 1
• Half-life of immediate-release is 3-4.5 hours 2

Transition from IV to Oral

• Administer first oral dose while IV infusion continues 5
• Discontinue IV infusion 4 hours after first oral dose 5
• Use median oral dose of 300 mg daily extended-release when transitioning from median IV infusion of 10 mg/hour 5
• 77% of patients maintain rate control during this transition 5

Target Heart Rate Goals

• Strict rate control: Resting heart rate <80 bpm (Class IIa recommendation) 1
• Lenient rate control: Resting heart rate <110 bpm may be reasonable in asymptomatic patients with preserved left ventricular function (Class IIb recommendation) 1
• Monitor heart rate during exertion and adjust dosing accordingly 1

Critical Contraindications (Absolute)

Do not administer diltiazem in the following situations:

• Decompensated heart failure or LVEF ≤40% 1, 2
• Pre-excited atrial fibrillation (WPW syndrome with accessory pathway conduction) 1, 2
• Second or third-degree AV block without pacemaker 1, 2
• Severe hypotension 1, 2
• Sick sinus syndrome without pacemaker 1

Common Adverse Effects and Monitoring

Hypotension

• Occurs in 18-42% of patients depending on dose 2, 4
• Monitor blood pressure continuously during IV administration 2
• Risk increases with higher doses and concurrent beta-blocker use 1, 4

Bradycardia and Heart Block

• Common adverse effects requiring continuous cardiac monitoring 1, 2
• Use with extreme caution when combining with beta-blockers 1

Negative Inotropic Effects

• Worsens heart failure in patients with pre-existing ventricular dysfunction 1, 2
• In heart failure patients, use digoxin or amiodarone instead 1, 2

Drug Interactions

• Diltiazem is a moderate CYP3A4 inhibitor and substrate 1
• Increases levels of: simvastatin, cyclosporine, digoxin (reduce digoxin dose by 30-50%), apixaban, rivaroxaban, dabigatran 1
• Avoid concurrent use with strong CYP3A4 inhibitors (itraconazole, clarithromycin) without dose adjustment 1

Special Populations

Hepatic Impairment

• Reduce dose and monitor closely due to hepatic metabolism 1
• Start with lower end of dosing range 1

Renal Impairment

• Start with smaller doses in renal impairment 1
• Monitor for accumulation with extended-release formulations 1

Elderly Patients

• Consider starting with lower doses (0.2 mg/kg IV or 120 mg oral daily) due to increased hypotension risk 4

Combination Therapy

• Diltiazem plus digoxin provides superior rate control compared to either agent alone, both at rest and during exercise 6
• Medium-dose diltiazem (240 mg/day) combined with digoxin is effective and safe for long-term management 6
• High-dose diltiazem (360 mg/day) causes side effects in 75% of patients and offers minimal additional benefit when combined with digoxin 6

Pharmacokinetic Considerations

• Plasma diltiazem concentration of 79 ng/mL produces 20% heart rate reduction 7
• Plasma concentration of 172 ng/mL produces 30% heart rate reduction 7
• Plasma concentration of 294 ng/mL produces 40% heart rate reduction 7
• Pharmacokinetics are nonlinear with dose-dependent decrease in clearance at higher infusion rates 7
• Elimination half-life after IV infusion is 6.8-6.9 hours 7