What is the recommended dosing for Diltiazem (Calcium Channel Blocker) in the treatment of hypertension?

From the Guidelines

Diltiazem for hypertension is typically started at 120 mg daily in divided or single dose with long-acting formulations, with a maximum daily dose of 360 mg. The dosing of Diltiazem can be adjusted based on blood pressure response, and it is essential to monitor patients for potential adverse effects such as hypotension, worsening heart failure, bradycardia, and abnormal liver function studies 1.

Key Considerations

• Diltiazem works by blocking calcium channels in vascular smooth muscle and cardiac tissue, causing vasodilation and reduced peripheral resistance, which lowers blood pressure.
• It also has mild negative chronotropic and inotropic effects on the heart.
• Patients should be monitored for common side effects including edema, headache, dizziness, and constipation.
• Diltiazem should be used cautiously in patients with heart failure, conduction abnormalities, or liver disease, and dose adjustments may be needed in elderly patients or those with hepatic impairment.

Dosing and Administration

• The initial daily dose of Diltiazem can be 120 mg daily in divided or single dose with long-acting formulations.
• The maintenance dose can be adjusted up to 360 mg daily in divided or single dose with long-acting formulations.
• Immediate-release formulations are not recommended as the first-line treatment, but if used, the dose can be 30 mg three to four times daily initially, with titration up to 360 mg daily in divided doses.

Special Considerations

• Diltiazem is a substrate of CYP3A4 (major) and a moderate CYP3A4 inhibitor, which can interact with other medications such as apixaban, itraconazole, bosutinib, ceritinib, cilostazol, cyclosporine, everolimus, ibrutinib, idelalisib, ivabradine, lomitapide, olaparib, ranolazine, rifampin, and simeprevir 1.
• The 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults recommends avoiding routine use of Diltiazem with beta blockers due to the increased risk of bradycardia and heart block 1.

From the FDA Drug Label

DOSAGE AND ADMINISTRATION Exertional Angina Pectoris Due to Atherosclerotic Coronary Artery Disease or Angina Pectoris at Rest Due to Coronary Artery Spasm: Dosage must be adjusted to each patient’s needs Starting with 30 mg four times daily, before meals and at bedtime, dosage should be increased gradually (given in divided doses three or four times daily) at 1- to 2-day intervals until optimum response is obtained. Although individual patients may respond to any dosage level, the average optimum dosage range appears to be 180 to 360 mg/day

The FDA drug label does not answer the question.

From the Research

Diltiazem Dosing for Hypertension

• The recommended dosing for Diltiazem in the treatment of hypertension varies, but studies suggest that a daily dose of up to 360 mg is optimal for controlling hypertension and ensuring patient compliance 2.
• A dose-response trial of once-daily diltiazem found that doses of 240-480 mg/day significantly lowered trough systolic and diastolic blood pressure in a clearly dose-related fashion 3.
• Another study found that diltiazem is generally underdosed, but when properly dosed, it may be the single most potent antihypertensive overall, with a clear linear dose-response relationship between diltiazem dose and blood pressure lowering through the 480-540 mg/day range 4.
• A dose-response trial of once-daily diltiazem CD capsules found that doses of 180,360, and 540 mg lowered both supine diastolic and systolic blood pressure, with a linear dose response seen with changes in diastolic and systolic blood pressure and heart rate for trough and peak measurements 5.

Diltiazem Dosage Ranges

• The effective dosage range for diltiazem in hypertension is typically between 180-360 mg/day, with some studies suggesting that higher doses (up to 540 mg/day) may be necessary for optimal blood pressure control 3, 5.
• A study found that the 90-120 mg/day range is the "no-effect dose" for diltiazem in hypertension, suggesting that higher doses are necessary for therapeutic efficacy 4.
• European data suggest that diltiazem doses of 180-270 mg/day produce a consistent antihypertensive effect throughout a 24-hour period 6.

Safety and Tolerability

• Diltiazem has been found to be safe and well-tolerated in patients with hypertension, with adverse events generally mild and similar to placebo 3, 5.
• Common adverse effects of diltiazem include headache, bradycardia, and edema, which may be dose-related 5.