Maximum Dose of Cardizem (Diltiazem)
The maximum recommended dose of Cardizem (diltiazem) is 360 mg daily for standard clinical use in hypertension and angina, though doses up to 480-540 mg daily have been studied and found safe in clinical trials for hypertension. 1, 2
Standard Maximum Dosing
For routine clinical practice, the maximum maintenance dose is 360 mg daily in divided doses for immediate-release formulations or as a single dose with long-acting formulations. 3, 1
The American College of Cardiology guidelines establish 120-360 mg daily as the standard therapeutic range for both hypertension and angina management. 1
Extended-release formulations (Cardizem CD) are dosed once daily from 180-420 mg, with most patients requiring 240-360 mg for adequate blood pressure control. 1
Higher Doses Studied in Clinical Trials
Doses up to 480-540 mg daily have been evaluated in FDA-approved clinical trials and demonstrated a clear linear dose-response relationship for blood pressure lowering without reaching a ceiling effect. 2, 4
A forced-escalation trial showed statistically significant blood pressure reductions at 360 mg/day and 540 mg/day, with dose escalations resulting in incremental blood pressure reductions and increased responder rates. 4
The 480 mg daily dose was studied in elderly patients (55+ years) with mild-to-moderate hypertension and found to be safe and effective. 5
Clinical Context for Dosing
Hypertension typically requires higher doses (up to 360 mg daily) compared to angina (typically 240 mg daily). 1, 2
Despite evidence supporting higher doses, prescribing patterns show that 70% of diltiazem prescriptions for hypertension use only 180-240 mg doses, representing systematic underdosing. 2
The 90-120 mg/day range represents a "no-effect dose" for hypertension based on pooled FDA trial data. 2
Formulation-Specific Considerations
Immediate-release tablets: 30-90 mg four times daily (maximum 360 mg/day total). 3
Extended-release/controlled-delivery formulations: 120-360 mg once daily, with some formulations studied up to 540 mg/day. 1, 4
The once-daily CD formulation maintains consistent blood levels over 24 hours with dosing ranging from 180-420 mg. 1
Critical Safety Monitoring at Higher Doses
Monitor blood pressure and heart rate closely during dose titration, particularly when exceeding 240 mg daily. 1
Watch for dose-related adverse effects including hypotension, bradycardia, peripheral edema, and constipation. 1
Absolute contraindications apply at all doses: second/third-degree AV block without pacemaker, decompensated heart failure, severe LV dysfunction, cardiogenic shock, and WPW syndrome with atrial fibrillation/flutter. 1, 6
Important Clinical Pitfalls
Never combine diltiazem with beta-blockers without extreme caution due to risk of significant bradyarrhythmias and heart failure. 1
Extended-release capsules cannot be split, crushed, or opened—if dose adjustment below 120 mg is needed, use immediate-release formulation. 7
Diltiazem is both a CYP3A4 substrate and moderate CYP3A4 inhibitor—exercise caution with medications like simvastatin, cyclosporine, and apixaban. 1
In patients with hepatic dysfunction, expect a 69% increase in drug exposure and prolonged half-life, necessitating dose reduction. 8