Diltiazem Dosing for Hypertension
For hypertension management, start diltiazem at 120-180 mg once daily using extended-release formulations and titrate to 240-360 mg daily, as most patients require doses in this range for adequate blood pressure control. 1
Initial Dosing Strategy
- Begin with 120-180 mg once daily of extended-release diltiazem for hypertension 1
- The immediate-release formulation starts at 30 mg four times daily (before meals and at bedtime), but extended-release is preferred for once-daily dosing 2
- Titrate gradually over 1-2 week intervals based on blood pressure response 1
Target Maintenance Doses
- Most hypertensive patients require 240-360 mg daily for adequate blood pressure control, which is higher than the typical 240 mg daily used for angina 1, 3
- Maximum studied dose is 540 mg daily, which has been shown safe and effective 4, 3
- Doses below 180 mg daily are generally insufficient for hypertension—the 90-120 mg/day range is essentially a "no-effect dose" for blood pressure lowering 3
- In clinical trials, 85% of hypertensive patients required 360 mg/day for optimal control 5
Available Formulations
- Extended-release (ER) or controlled-delivery (CD) formulations: 120-540 mg once daily 1
- Immediate-release tablets: 30-120 mg, dosed 3-4 times daily 2
- Once-daily extended-release formulations are preferred for consistent 24-hour blood pressure control 1, 4
Dose-Response Relationship
- Clear linear dose-response exists through 480-540 mg/day range for blood pressure lowering 3
- Peak and trough plasma concentrations correlate significantly with antihypertensive effects 4
- Trough drug levels ≥40 ng/mL (achieved with ≥240 mg/day) are needed for therapeutic effect 4
Absolute Contraindications
Do not use diltiazem in patients with: 6, 1
- Second or third-degree AV block without a functioning pacemaker
- Sick sinus syndrome without a pacemaker
- Decompensated systolic heart failure or severe LV dysfunction (LVEF <40%)
- Cardiogenic shock
- Wolff-Parkinson-White syndrome with atrial fibrillation/flutter
- Hypotension (systolic BP <90 mmHg)
Critical Precautions
- Avoid combining with beta-blockers due to increased risk of profound bradycardia, AV block, and heart failure 1, 7
- Use caution in hepatic dysfunction—diltiazem is hepatically metabolized and may require dose reduction 6
- Reduce dose in renal impairment, though diltiazem appears safe in this population 1, 4
- Diltiazem is both a CYP3A4 substrate and moderate CYP3A4 inhibitor—exercise caution with apixaban, rivaroxaban, simvastatin, cyclosporine, and other CYP3A4 substrates 6, 1
Common Adverse Effects
- Peripheral edema (dose-related, more common in women)—consider adding diuretics if problematic 1
- Hypotension (most common with IV administration) 6
- Bradycardia 6
- Dizziness, headache, gastrointestinal upset 6
- Constipation 1
Monitoring Requirements
- Blood pressure and heart rate at each visit during titration 1
- Assess for signs/symptoms of heart failure in at-risk patients 1
- Liver function tests if clinically indicated 6
- ECG monitoring in patients with conduction system disease 1
Clinical Pearls
- Diltiazem is often underdosed in clinical practice—70% of prescriptions are for 180-240 mg despite most patients requiring 360 mg for hypertension 3
- Tends to be more effective in older patients without increased orthostatic hypotension 5
- Preferred over dihydropyridines when baseline heart rate is elevated, as it reduces heart rate at rest and during exercise 1
- No negative effect on glycemic control in diabetic patients 8
- Can be safely combined with ACE inhibitors/ARBs and thiazide diuretics for additional blood pressure control 1
Common Pitfall to Avoid
The single most common error is using angina doses (240 mg) for hypertension—this stems from physicians becoming accustomed to lower antianginal doses before the hypertension indication was approved, and capsule size limitations of early formulations 3. Most hypertensive patients need 360 mg daily for adequate control.