What is the recommended dosage and treatment approach for Diltiazem (Diltiazem) XR for high blood pressure and angina?

Diltiazem XR Dosing for Hypertension and Angina

For hypertension, start diltiazem XR at 180-240 mg once daily and titrate up to 360-480 mg daily for optimal blood pressure control; for angina, start at 120-180 mg once daily and titrate to 240-360 mg daily, with most patients achieving symptom relief at 240 mg daily. 1, 2, 3

Initial Dosing Strategy

For Hypertension

• Start at 180-240 mg once daily using extended-release formulations 1, 4
• The 120 mg dose is essentially a "no-effect dose" for hypertension and should not be used 3
• Titrate upward every 1-2 weeks based on blood pressure response 1, 2
• Target maintenance dose: 360-480 mg once daily for most patients with hypertension 1, 3, 4
• Maximum dose studied effectively: 540 mg daily, though 360-480 mg is typically sufficient 4, 5

For Angina

• Start at 120-180 mg once daily with extended-release formulations 1, 2
• Immediate-release formulation alternative: 30 mg four times daily, titrated at 1-2 day intervals 2
• Target maintenance dose: 240 mg daily for most angina patients 3, 6
• Range of 180-360 mg daily is effective, with 360 mg providing maximal benefit in some patients 2, 6

Critical Clinical Context: When to Use Diltiazem

Appropriate Clinical Scenarios

• Use as a beta-blocker substitute when beta-blockers are contraindicated or cause intolerable side effects in patients with stable angina and hypertension, but NOT if left ventricular dysfunction is present 7
• Consider for patients with coronary artery disease who cannot tolerate first-line agents (beta-blockers, ACE inhibitors/ARBs, thiazides) 7
• May add to existing beta-blocker therapy for uncontrolled angina or hypertension, but use with extreme caution due to bradyarrhythmia and heart failure risk 7

Absolute Contraindications

• Second or third-degree AV block without functioning pacemaker 1, 2
• Sick sinus syndrome without pacemaker 1
• Decompensated systolic heart failure or severe LV dysfunction 7, 1
• Wolff-Parkinson-White syndrome with atrial fibrillation/flutter 1
• Cardiogenic shock 1
• Hypotension 1

Dosing Titration Algorithm

Step 1: Assess Patient Characteristics

• Verify absence of contraindications (LV dysfunction, conduction abnormalities, hypotension) 1
• Check for hepatic or renal impairment requiring cautious titration 1, 2
• Review concurrent medications, especially CYP3A4 inhibitors/substrates and other AV nodal blockers 1

Step 2: Initiate Therapy

• Hypertension: 180-240 mg once daily 1, 4
• Angina: 120-180 mg once daily 1, 2
• Use extended-release formulations (CD, XR) for once-daily dosing 1

Step 3: Titrate to Effect

• Reassess at 2-4 weeks after initiation or dose change 1, 4
• For hypertension: Increase by 60-120 mg increments until blood pressure goal achieved or maximum dose reached 4, 5
• For angina: Increase by 60 mg increments if symptoms persist, typically stopping at 240 mg daily 6
• Monitor blood pressure, heart rate, and symptoms at each visit 1

Step 4: Maintenance Dosing

• Hypertension: Most patients require 360-480 mg daily for optimal control 3, 4, 5
• Angina: Most patients achieve symptom relief at 240 mg daily 3, 6
• Maximum studied dose: 540 mg daily, though rarely necessary 4

Blood Pressure Targets

• Standard target for stable angina with hypertension: <140/90 mm Hg 7
• Consider lower target of <130/80 mm Hg in select patients with CAD, prior stroke/TIA, or CAD equivalents (carotid disease, PAD, abdominal aortic aneurysm) 7
• Avoid lowering diastolic blood pressure below 60 mm Hg, as this may worsen myocardial ischemia 7

Common Pitfalls and How to Avoid Them

Underdosing for Hypertension

• The most common error is using 180-240 mg daily for hypertension, which is inadequate for most patients 3
• This stems from historical use of lower doses for angina before hypertension indication was approved 3
• Solution: Start at 240 mg and plan to titrate to 360-480 mg for hypertension 3, 4

Combining with Beta-Blockers

• High risk of severe bradycardia and heart block when diltiazem is combined with beta-blockers 7
• If combination is necessary, use with extreme caution and close monitoring 7
• Safer alternative: Use a long-acting dihydropyridine CCB (amlodipine, felodipine) with beta-blocker instead 7

Missing LV Dysfunction

• Diltiazem has negative inotropic effects and can precipitate or worsen heart failure 7, 1
• Always assess LV function before initiating diltiazem in patients with history of MI, dyspnea, or other heart failure symptoms 7, 1
• If LV dysfunction present, use beta-blockers or dihydropyridine CCBs (amlodipine) instead 7

Drug Interactions

• Diltiazem is a CYP3A4 substrate and moderate inhibitor 1
• Use caution with: apixaban, cyclosporine, simvastatin, rifampin, itraconazole, and many other medications 1
• Monitor for increased drug levels of CYP3A4 substrates when adding diltiazem 1

Monitoring Requirements

Initial Phase (First 4-8 Weeks)

• Blood pressure and heart rate at each visit (every 2-4 weeks during titration) 1
• Assess for symptoms of hypotension, bradycardia, or heart failure 1
• ECG if patient has any conduction system disease 1

Maintenance Phase

• Blood pressure and heart rate at routine follow-up visits 1
• Watch for peripheral edema (dose-related, more common in women) 1
• Liver function tests if clinically indicated (rare hepatotoxicity) 1
• Signs/symptoms of heart failure in at-risk patients 1

Adverse Effects Management

Peripheral Edema

• Dose-related and more common in women 1
• Consider adding a diuretic rather than discontinuing diltiazem 1

Bradycardia

• May be dose-limiting 1
• Reduce dose or discontinue if symptomatic or heart rate <50 bpm 1

Constipation

• Common, especially in elderly patients 8
• May require dose reduction or discontinuation in severe cases 8

Hypotension

• Most common adverse effect overall 1
• Reduce dose if symptomatic or blood pressure excessively low 1