What is the recommended diltiazem dosing regimen (intravenous loading dose, repeat bolus, continuous infusion, and oral maintenance) for rate control in an adult patient with atrial fibrillation?

Diltiazem Dosing for Rate Control in Atrial Fibrillation

For acute rate control in atrial fibrillation, administer diltiazem 0.25 mg/kg IV (approximately 20 mg for average adults) over 2 minutes, followed by a second bolus of 0.35 mg/kg (approximately 25 mg) after 15 minutes if needed, then initiate continuous infusion at 10 mg/hour (range 5–15 mg/hour) for up to 24 hours, and transition to oral extended-release diltiazem 180–360 mg once daily for maintenance. 1, 2

Intravenous Loading Dose

• Initial bolus: Administer 0.25 mg/kg actual body weight IV over 2 minutes (20 mg is reasonable for average-weight patients). 1, 2
• Onset of action: Expect heart rate reduction within 2–7 minutes after IV administration. 1, 3
• Patients with low body weight should be dosed on a mg/kg basis rather than using fixed doses. 2

Repeat Bolus Dosing

• Second bolus: If inadequate response after 15 minutes, administer 0.35 mg/kg IV over 2 minutes (25 mg is reasonable for average-weight patients). 1, 2
• Some patients may respond to a lower initial dose of 0.15 mg/kg, though duration of action may be shorter and experience is limited. 2
• Evidence note: Low-dose diltiazem (≤0.2 mg/kg) achieves similar rate control (70.5% response) compared to standard dose (77.1% response) but with significantly lower hypotension risk (18% vs 34.9%). 4

Continuous Infusion Protocol

• Initial infusion rate: Start at 10 mg/hour immediately after bolus administration and heart rate reduction. 1, 2
• Alternative starting rate: Some patients maintain response with 5 mg/hour. 1, 2
• Titration: Increase in 5 mg/hour increments up to a maximum of 15 mg/hour if further heart rate reduction is needed. 1, 3, 2
• Duration: Maintain infusion for up to 24 hours; infusions exceeding 24 hours and rates exceeding 15 mg/hour have not been studied and are not recommended. 1, 2
• Pharmacokinetic consideration: Diltiazem exhibits dose-dependent, non-linear pharmacokinetics with apparent dose-dependent decrease in systemic clearance at higher infusion rates. 5, 6

Transition to Oral Maintenance Therapy

• Timing: Initiate oral diltiazem after achieving stable heart rate control (heart rate <100 bpm or ≥20% reduction from baseline) for at least 15–30 minutes. 3
• Discontinue infusion: Stop IV infusion 4 hours after the first oral dose. 7

Oral Dosing Options

Extended-release formulation (preferred):

• Start with 180–300 mg once daily; usual maintenance range 180–360 mg once daily. 1, 3
• Extended-release tablets provide consistent 24-hour drug delivery. 8
• The median effective oral dose in clinical studies was 300 mg/day. 7

Immediate-release formulation:

• Dose 120–360 mg daily in divided doses (typically 30–90 mg every 6 hours). 1, 3
• Half-life is 3–4.5 hours for immediate-release versus 4–9.5 hours for extended-release. 1

Target Heart Rate Goals

• Lenient control: Resting heart rate <100 bpm. 3
• Strict control: Resting heart rate 60–80 bpm. 3
• Alternative definition: ≥20% reduction from baseline heart rate. 7, 6

Absolute Contraindications

• Heart failure with reduced ejection fraction (LVEF ≤40%): Diltiazem has negative inotropic effects and is contraindicated in HFrEF. 1, 3
• Pre-excited atrial fibrillation (Wolff-Parkinson-White syndrome): May accelerate ventricular response and precipitate ventricular fibrillation. 1, 8, 3
• Second- or third-degree AV block without functioning pacemaker: Risk of complete heart block. 1, 8, 3
• Sick sinus syndrome without pacemaker: May worsen bradycardia. 8, 3
• Severe hypotension (systolic BP <90 mmHg): Diltiazem causes vasodilation. 8, 3
• Decompensated heart failure or cardiogenic shock: Negative inotropic effects worsen hemodynamics. 1, 8, 3

Critical Precautions

• Avoid concurrent beta-blocker use: Combination significantly increases risk of profound bradycardia, AV block, and heart failure. 8, 3
• First-degree AV block (PR >0.24 seconds): Use with extreme caution; may progress to higher-degree block. 8
• Hepatic dysfunction: Diltiazem is metabolized by the liver; dose adjustment may be required. 8

Common Adverse Effects

• Hypotension: Occurs in 18–42% of patients depending on dose; significantly more common with standard doses (≥0.25 mg/kg) versus low doses (<0.2 mg/kg). 3, 4
• Bradycardia: Monitor continuously during administration. 1, 3
• Heart block: Risk increases with higher doses and concurrent AV nodal blocking agents. 3
• Peripheral edema: Dose-related effect, more common in women. 8

Monitoring Requirements

• Continuous monitoring: Heart rate and blood pressure during IV administration. 3
• Target verification: Confirm heart rate <100 bpm or ≥20% reduction from baseline. 3, 7
• Blood pressure: Monitor for hypotension; lowest recorded values in studies were SBP 90 mmHg and DBP 47 mmHg without requiring discontinuation. 9
• ECG monitoring: Essential in patients with conduction system disease. 8
• Transition monitoring: Observe continuously for first 2–4 hours after starting oral therapy. 3

Drug Interactions

• CYP3A4 substrates: Diltiazem is a moderate CYP3A4 inhibitor; monitor levels of apixaban, rivaroxaban, simvastatin, and cyclosporine. 8
• Digoxin: Reduce dose by 30–50% when initiating diltiazem. 8
• Warfarin: Reduce dose by 50% when starting diltiazem. 8

Clinical Pearls

• Class I recommendation: Diltiazem carries the highest level of evidence (Class I, Level B) for acute rate control in atrial fibrillation. 3
• Efficacy data: 94% of patients respond to initial bolus with ≥20% heart rate reduction, and 77% maintain control during transition to oral therapy. 7, 6
• Dose-response relationship: Plasma concentrations of 79,172, and 294 ng/mL produce 20%, 30%, and 40% heart rate reductions, respectively. 5
• Weight-based dosing advantage: Diltiazem ≥0.13 mg/kg achieves heart rate control in mean 169 minutes versus 318 minutes for <0.13 mg/kg, with 61% versus 36% achieving control within 240 minutes. 9
• Alternative in heart failure: Use digoxin or amiodarone instead of diltiazem for rate control in patients with reduced ejection fraction. 3