What is the recommended titration protocol for Cardizem (Diltiazem)?

Diltiazem Titration Protocol

Oral Formulations for Chronic Indications

For hypertension, start diltiazem at 120-180 mg once daily using extended-release formulations, and titrate upward every 1-2 weeks to a target of 240-360 mg daily, with doses up to 540 mg/day proven safe and effective for blood pressure control. 1, 2

Initial Dosing Strategy

• Immediate-release tablets: Start at 30 mg four times daily (before meals and bedtime), increasing gradually at 1-2 day intervals until optimal response 3
• Extended-release/CD formulations: Begin at 120-180 mg once daily, which provides controlled delivery over 24 hours 1, 4
• Slow-release preparations: Can be dosed at 120-360 mg daily in 2-3 divided doses 1

Titration Schedule

• Hypertension: Titrate cautiously and progressively over several weeks, increasing dose every 1-2 weeks based on blood pressure response 1, 3
• Target doses: 240-360 mg daily for hypertension (commonly requires higher doses than angina) 1, 5
• Maximum dose: Up to 540 mg/day has been studied and found safe for hypertension, with clear dose-response relationship through this range 5, 2
• Angina: Typically requires lower doses (commonly 240 mg/day) compared to hypertension 5

Critical Monitoring During Titration

• Monitor blood pressure and heart rate regularly at each dose adjustment 1
• Reassess patients 1 month after initiation or dose change 1
• Watch for common adverse effects: hypotension, bradycardia, peripheral edema, and constipation 1
• Check for bradycardia, which may be dose-limiting 1

Intravenous Formulations for Acute Rate Control

For acute supraventricular tachycardia or rapid atrial fibrillation, administer 0.25 mg/kg (15-20 mg for average adults) IV over 2 minutes, followed by 0.35 mg/kg (20-25 mg) after 15 minutes if needed, then start continuous infusion at 5 mg/hour and titrate up to 15 mg/hour based on heart rate response. 6, 7

IV Bolus Protocol

• First dose: 0.25 mg/kg (approximately 15-20 mg) IV over 2 minutes 6, 7
• Second dose: 0.35 mg/kg (20-25 mg) may be given 15 minutes after first dose if no therapeutic response 6, 7
• Lower doses may be safer: Evidence suggests doses ≤0.2 mg/kg are as effective as standard doses but with significantly lower hypotension rates (18% vs 35%) 8

Continuous Infusion

• Start at 5 mg/hour and titrate up to 15 mg/hour based on heart rate response 6
• Requires continuous ECG monitoring and frequent blood pressure measurements 6
• Have defibrillator and resuscitation equipment immediately available 6

Absolute Contraindications

Never use diltiazem in the following situations:

• Second or third-degree AV block without functioning pacemaker 1, 6, 7
• Sick sinus syndrome without pacemaker 1, 6
• Wolff-Parkinson-White syndrome with atrial fibrillation/flutter (may cause hemodynamic collapse) 1, 6
• Decompensated systolic heart failure or severe LV dysfunction 1, 6
• Cardiogenic shock or hypotension (systolic BP <90 mmHg) 1, 6

Critical Precautions

• Avoid routine combination with beta-blockers due to risk of profound bradycardia, heart block, and heart failure 9, 1, 6
• Use extreme caution in patients with PR interval >0.24 seconds 1
• Exercise caution in hepatic or renal dysfunction (diltiazem is metabolized by liver) 1
• Drug interactions: Diltiazem is both a CYP3A4 substrate and moderate inhibitor; reduce warfarin dose by 50% and digoxin by 30-50% when initiating 1

Common Pitfalls to Avoid

• Underdosing for hypertension: Most prescriptions are for 180-240 mg, but hypertension typically requires 360 mg daily or higher for optimal control 5
• Using in wide-complex tachycardia: Never use unless arrhythmia is known with certainty to be supraventricular in origin 1
• Stopping abruptly: Should not be discontinued suddenly unless absolutely necessary 9
• Ignoring asymptomatic hypotension: Blood pressure of 115/60 mmHg does not require dose adjustment if patient is asymptomatic 1

Special Clinical Situations

• Peripheral edema: Dose-related and more common in women; consider adding diuretics rather than stopping diltiazem 1
• Baseline tachycardia: Diltiazem is preferred over dihydropyridines in patients with relative tachycardia 1
• Elderly patients: Effective and well-tolerated in patients 65-85 years with mild-to-moderate hypertension 1