What is the typical dosing for Dilt-XR (Diltiazem)?

Diltiazem Extended-Release (Dilt-XR) Dosing

For hypertension, start diltiazem extended-release at 180-240 mg once daily and titrate up to 360-540 mg daily as needed for blood pressure control, while for angina, start at 120-180 mg once daily with a typical maintenance dose of 240 mg daily. 1, 2

Initial Dosing Strategy

For Hypertension

• Start at 180-240 mg once daily for extended-release formulations (Cardizem CD or equivalent) 1, 3
• The 120 mg dose represents a "no-effect dose" for hypertension and should not be used as monotherapy for blood pressure control 4, 3
• Peak plasma levels occur 2-4 hours after administration, with therapeutic levels maintained over 24 hours 2

For Angina Pectoris

• Start at 120-180 mg once daily for extended-release formulations 1, 5
• Lower doses are effective for angina compared to hypertension due to different mechanisms (coronary vasodilation vs. systemic blood pressure reduction) 2, 4

Dose Titration and Maintenance

Hypertension Management

• Titrate cautiously over 2-4 weeks to achieve blood pressure control 1
• Target maintenance dose: 360 mg daily, with maximum doses up to 540 mg daily if needed 1, 3
• There is a clear linear dose-response relationship through the 480-540 mg/day range for blood pressure lowering 4, 3
• Common pitfall: Diltiazem is frequently underdosed for hypertension, with 70% of prescriptions being 180-240 mg despite evidence supporting higher doses 4

Angina Management

• Typical maintenance dose: 240 mg daily 1, 4
• Maximum dose: 360 mg daily if needed 1, 5
• Both 240 mg and 360 mg doses significantly reduce anginal attacks and improve exercise tolerance compared to placebo 5

Formulation-Specific Considerations

Extended-Release (CD) Formulations

• Designed for once-daily administration with 24-hour coverage 1, 2
• Available strengths: 120 mg, 180 mg, 240 mg, 300 mg, 360 mg, and 420 mg 1
• Cannot be split, crushed, or chewed - must be swallowed whole 6
• Therapeutic plasma levels (≥40-50 ng/mL) are achieved with doses ≥240 mg/day 2, 3

Immediate-Release Formulations

• Available in 30-90 mg tablets 1
• Requires multiple daily dosing (typically 3-4 times daily) 2
• Less commonly used due to inconvenience compared to extended-release formulations 1

Contraindications and Precautions

Absolute Contraindications

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

Use with Caution

• Avoid routine combination with beta-blockers due to increased risk of bradycardia and heart block 7, 1
• Hepatic dysfunction: Diltiazem undergoes extensive hepatic metabolism; patients with cirrhosis show 69% increase in drug exposure 2
• Renal dysfunction: No significant pharmacokinetic changes, but monitor closely 2
• First-degree AV block: Monitor ECG, though diltiazem does not disproportionately worsen conduction 2

Drug Interactions

CYP3A4 Considerations

• Diltiazem is both a CYP3A4 substrate (major) and moderate CYP3A4 inhibitor 1
• Use caution with: apixaban, itraconazole, bosutinib, ceritinib, cilostazol, cyclosporine, everolimus, ibrutinib, idelalisib, ivabradine, lomitapide, olaparib, ranolazine, rifampin, simeprevir 1
• Rifampin (CYP3A4 inducer) may significantly reduce diltiazem levels 1

Other Notable Interactions

• Digoxin, warfarin, propranolol: No significant protein binding displacement 2
• Statins metabolized by CYP3A4 (simvastatin, lovastatin): Increased risk of myopathy 1

Monitoring Requirements

Essential Parameters

• Blood pressure and heart rate at each visit during titration 1
• ECG monitoring in patients with conduction system disease 1
• Liver function tests if clinically indicated (not routine) 1
• Signs and symptoms of heart failure in at-risk patients 1

Follow-up Schedule

• Reassess in 1 month after initiation or dose change 7
• Monitor for return of symptoms (elevated blood pressure, angina, rapid heart rate) 6

Common Adverse Effects

Most Frequent

• Hypotension - most common adverse effect 1
• Peripheral edema - dose-related, more common in women; consider adding diuretics 7, 1
• Bradycardia - may be dose-limiting 1
• Constipation - particularly in elderly patients 1, 8

Serious but Rare

• Worsening heart failure in patients with pre-existing ventricular dysfunction 1, 2
• Acute hepatic injury - monitor if symptoms develop 1
• Significant bradyarrhythmias - especially when combined with beta-blockers 7, 1

Special Populations

Elderly Patients

• Consider starting at lower end of dosing range (180 mg daily) 8
• Elderly patients (71-82 years) with angina showed optimal response at 180 mg/day with increased adverse effects at higher doses 8
• Constipation is particularly problematic in this population and may require dose reduction 8

Patients with Relative Tachycardia

• Diltiazem is preferred over dihydropyridines (nifedipine, amlodipine) in patients with baseline tachycardia 7, 1
• Reduces heart rate at rest and during exercise 2

Discontinuation

Stopping Diltiazem

• Unlike beta-blockers, diltiazem does not require gradual tapering 6
• No significant withdrawal syndrome or rebound hypertension/tachycardia 6
• Simply stop the medication and monitor blood pressure and heart rate for 1-2 weeks 6
• Do not attempt to split or crush extended-release capsules 6