How do I convert a patient from immediate-release Cardizem (diltiazem) to an extended-release formulation?

Converting from Immediate-Release to Extended-Release Diltiazem

Convert directly on a milligram-for-milligram basis from immediate-release to extended-release diltiazem, or to the next higher available dose if an exact match is unavailable. 1

Conversion Strategy

Direct 1:1 conversion is the recommended approach:

• Calculate the patient's total daily dose of immediate-release diltiazem (e.g., if taking 60 mg four times daily = 240 mg/day total) 2
• Switch to the same total daily dose of extended-release formulation given once daily (e.g., 240 mg ER once daily) 1
• If the exact dose is not available in extended-release form, round up to the next higher 120 mg increment (e.g., if on 200 mg/day immediate-release, convert to 240 mg ER) 1

Evidence Supporting Direct Conversion

A multicenter study of 195 patients with chronic stable angina demonstrated that direct mg-for-mg conversion from immediate-release to extended-release diltiazem resulted in:

• Statistically significant decrease in angina frequency and nitroglycerin consumption 1
• Maintained therapeutic efficacy with no increase in adverse reactions 1
• Similar outcomes whether converted exactly mg-for-mg or to the next higher available dose 1

Available Extended-Release Formulations

Dosing options for extended-release diltiazem:

• Starting dose: 120-180 mg once daily 3, 4
• Usual maintenance range: 120-360 mg once daily 3
• Maximum studied dose: 540 mg once daily (safe and effective for hypertension) 5, 6
• Extended-release formulations provide consistent 24-hour drug delivery 5

Pharmacokinetic Considerations

Key differences between formulations:

• Immediate-release half-life: 4.5-12 hours 3
• Extended-release half-life: 12 hours 3
• Immediate-release requires 3-4 times daily dosing; extended-release allows once-daily administration 2, 3
• Extended-release formulations show disproportionate increases in drug exposure as doses increase from 120 mg to 540 mg daily, supporting once-daily efficacy 5

Post-Conversion Monitoring

Monitor the following parameters after conversion:

• Blood pressure and heart rate at 1 month after conversion 4
• Return of symptoms including elevated blood pressure, angina episodes, or rapid heart rate 4
• Signs of hypotension, bradycardia, or conduction abnormalities 4
• Worsening heart failure in patients with pre-existing ventricular dysfunction 3, 4

Critical Contraindications to Verify Before Conversion

Do not convert if the patient has:

• Second- or third-degree AV block without a functioning pacemaker 3, 4
• Sick sinus syndrome without a pacemaker 3, 4
• Decompensated systolic heart failure or severe left ventricular dysfunction 3, 4
• Hypotension (systolic BP <90 mmHg) 4
• Wolff-Parkinson-White syndrome with atrial fibrillation/flutter 3, 4

Important Warnings About Extended-Release Formulations

Never split, crush, or chew extended-release capsules - they are designed for controlled 24-hour release and altering the formulation destroys this mechanism 7

Exercise extreme caution when combining with beta-blockers due to increased risk of significant bradyarrhythmias, profound AV block, and heart failure 3, 4

Drug Interaction Management

Diltiazem is both a CYP3A4 substrate and moderate CYP3A4 inhibitor, requiring careful attention to:

• Reduce warfarin dose by 50% when initiating diltiazem 4
• Reduce digoxin dose by 30-50% when initiating diltiazem 4
• Monitor levels of apixaban, rivaroxaban, simvastatin, cyclosporine, and other CYP3A4 substrates 3, 4