Adult Dosing Recommendations for PO Diltiazem XL
For oral extended-release diltiazem (XL), the recommended starting dose is 120-240 mg once daily, which can be titrated up to 360 mg once daily for hypertension and angina. 1
Dosing by Indication
Hypertension
- Starting dose: 120-240 mg once daily
- Titration: Can increase up to 360 mg once daily
- Median effective dose: 300 mg/day 1
- Maximum dose: Evidence supports efficacy through 480-540 mg/day range for hypertension 2
Angina
- Starting dose: 120 mg once daily
- Titration: Can increase up to 240-360 mg once daily 1
- Note: Lower doses are typically needed for angina (commonly 240 mg/day) compared to hypertension (commonly 360 mg/day) 2
Pharmacokinetics
- Well absorbed from GI tract (98% absorption)
- Subject to extensive first-pass metabolism (40% bioavailability)
- Plasma elimination half-life: 3.0-4.5 hours
- Therapeutic plasma levels: 50-200 ng/mL
- Protein binding: 70-80% 3
Dosing Considerations
Dose-Response Relationship
- Clear linear dose-response relationship exists between diltiazem dose and blood pressure lowering through 480-540 mg/day range 2
- Doses of 90-120 mg/day represent a "no-effect dose" for hypertension 2
- Multiple studies confirm that higher doses (300-420 mg) provide better response rates for hypertension 4
Special Populations
- Hepatic impairment: Increased half-life and 69% increase in AUC; dose adjustment may be needed 3
- Renal impairment: No significant difference in pharmacokinetics compared to normal renal function 3
Contraindications
- Left ventricular dysfunction (LVEF <40%)
- Decompensated heart failure
- AV block greater than first degree
- Sick sinus syndrome
- Cardiogenic shock
- Pre-excitation syndromes (e.g., Wolff-Parkinson-White syndrome) 1
- Should not be used in patients with HFrEF (heart failure with reduced ejection fraction) 5
Monitoring
- Blood pressure response
- Heart rate and cardiac conduction
- Signs of fluid retention (edema)
- Symptoms of hypotension or bradycardia 1
Common Side Effects
- Hypotension
- Dizziness
- Flushing
- Bradycardia
- Edema 1
Clinical Pearls
- Diltiazem is often underdosed in hypertension treatment; higher doses (>240 mg) are typically needed for optimal blood pressure control 2
- Trough/peak ratios for once-daily doses of 180 mg and higher are >0.50, confirming 24-hour efficacy 6
- Avoid combining with beta-blockers due to increased risk of bradycardia and heart block 1
- Do not use in patients with pre-excited atrial fibrillation or flutter as it may accelerate ventricular response 5