What are the guidelines for prescribing Diltiazem (calcium channel blocker) and Verapamil (calcium channel blocker) to patients with hypertension, angina, or arrhythmias?

Guidelines for Prescribing Diltiazem and Verapamil

Dosing Recommendations

For hypertension and angina, start diltiazem at 120-180 mg once daily (extended-release) or 30-90 mg four times daily (immediate-release), titrating up to a maximum of 360 mg daily; verapamil should be initiated at 80-160 mg three times daily (immediate-release) or 120-240 mg once daily (sustained-release), with a maximum of 480 mg daily. 1, 2

Diltiazem Dosing Specifics

• Immediate-release formulation: 30-90 mg four times daily 1
• Extended-release formulation: 120-360 mg once daily, with some studies supporting doses up to 540 mg/day for hypertension 2
• Hypertension typically requires higher doses (240-360 mg daily) compared to angina (typically 240 mg daily) 2
• Initial dose: 120 mg daily in divided doses or as single dose with long-acting formulations 2

Verapamil Dosing Specifics

• Immediate-release: 80-160 mg three times daily 1
• Sustained-release: 120-480 mg once daily 1
• Titrate cautiously over several weeks to achieve blood pressure control 2

Absolute Contraindications

Both diltiazem and verapamil are absolutely contraindicated in patients with second- or third-degree AV block without a functioning pacemaker, sick sinus syndrome without a pacemaker, severe left ventricular dysfunction or decompensated heart failure, hypotension (systolic BP <90 mmHg), and Wolff-Parkinson-White syndrome with atrial fibrillation/flutter. 3, 4, 2

Additional Contraindications

• Diltiazem-specific: Acute myocardial infarction with pulmonary congestion documented by x-ray 3
• Verapamil-specific: Cardiogenic shock 4
• Both agents: Known hypersensitivity to the respective drug 3, 4

Critical Precautions and Relative Contraindications

Combination with Beta-Blockers

Exercise extreme caution when combining diltiazem or verapamil with beta-blockers due to increased risk of significant bradyarrhythmias, profound AV block, and heart failure. 2, 5 This combination may act synergistically to depress left ventricular function and sinus/AV node conduction 1

Heart Failure Considerations

• Avoid in patients with pulmonary edema or severe LV dysfunction 1
• Retrospective analyses suggest verapamil and diltiazem can have detrimental effects on mortality in patients with LV dysfunction 1
• However, subsequent prospective trials with verapamil in MI patients with heart failure receiving ACE inhibitors suggested potential benefit 1
• Amlodipine and felodipine are better tolerated in patients with mild LV dysfunction, though their use in unstable angina/NSTEMI has not been studied 1

Conduction System Disease

• First-degree AV block with PR interval >0.24 seconds is a contraindication in acute coronary syndromes 2
• Monitor ECG in patients with conduction system disease 2

Clinical Indications and Evidence Base

Unstable Angina/NSTEMI

When beta-blockers cannot be used and in the absence of clinically significant LV dysfunction, heart rate-slowing calcium channel blockers (verapamil and diltiazem) are preferred for symptom control. 1

• The evidence base in UA/NSTEMI is greatest for verapamil and diltiazem 1
• The Diltiazem Reinfarction Study (576 patients) showed diltiazem reduced reinfarction and refractory angina at 14 days without increasing mortality 1
• The DAVIT trial (3,447 patients) showed trends toward reduced death or nonfatal MI with verapamil 1
• Definitive evidence for benefit is predominantly limited to symptom control 1

Atrial Fibrillation Rate Control

Verapamil and diltiazem are effective for ventricular rate control in atrial fibrillation, with beta-blockers being the most effective drug class overall. 1

• Intravenous diltiazem: 0.25 mg/kg (approximately 15-20 mg) over 2 minutes, with possible repeat dose of 0.35 mg/kg after 15 minutes if needed 5
• Diltiazem and verapamil provide better rate control than digoxin, especially during exercise 1
• These agents may be preferred over beta-blockers in patients with bronchospasm or chronic obstructive pulmonary disease 1

Hypertension

• Both agents are effective for hypertension, particularly in low-renin hypertension such as in elderly and Black populations 6
• Diltiazem may be preferred over dihydropyridines in patients with baseline tachycardia 2
• Can be combined with ACE inhibitors/ARBs and thiazide diuretics if needed for blood pressure control 2

Important Drug Interactions

Both diltiazem and verapamil are CYP3A4 substrates and moderate CYP3A4 inhibitors, requiring caution with numerous medications. 2

Key Interactions to Monitor

• Anticoagulants: Reduce warfarin dose by 50% when initiating diltiazem 2
• Cardiac glycosides: Reduce digoxin dose by 30-50% when starting diltiazem 2
• Statins: Exercise caution with simvastatin due to increased myopathy risk 2
• Other CYP3A4 substrates: Apixaban, rivaroxaban, cyclosporine, everolimus, itraconazole, bosutinib, ceritinib, cilostazol, ibrutinib, idelalisib, ivabradine, lomitapide, olaparib, ranolazine 2

Common Adverse Effects and Monitoring

Most Frequent Side Effects

• Hypotension (most common, especially with IV administration) 2, 5
• Peripheral edema (dose-related, more common in women; consider adding diuretics) 2
• Bradycardia 1, 2
• Dizziness and flushing 1
• Constipation (particularly with verapamil) 1

Monitoring Requirements

• Blood pressure and heart rate regularly during dose titration 2
• Signs and symptoms of heart failure in at-risk patients 2
• Liver function tests if clinically indicated 2
• ECG monitoring in patients with conduction system disease 2

Special Clinical Situations

Acute Coronary Syndromes

Diltiazem and verapamil should not be used routinely in STEMI; in non-STEMI/unstable angina, use only when beta-blockers are contraindicated AND there is no severe LV dysfunction. 2

• Never use immediate-release nifedipine in acute coronary syndromes without concomitant beta-blockade due to increased mortality 1, 2
• The Holland Interuniversity Nifedipine/metoprolol Trial was stopped early due to harm with nifedipine alone 1

Cocaine-Associated ACS

Do not use diltiazem as first-line therapy; reserve for patients unresponsive to benzodiazepines and nitroglycerin, and avoid in patients with heart failure or LV dysfunction. 2

Supraventricular Tachycardia

• Adenosine is first-line; diltiazem is an excellent second-line option 5
• IV diltiazem: 0.25 mg/kg over 2 minutes for acute PSVT 5
• Contraindicated in pre-excited atrial fibrillation/flutter (WPW syndrome) 5

Clinical Pearls and Pitfalls

Key Practice Points

• Asymptomatic low blood pressure (e.g., 115/60 mmHg) does not usually require medication adjustment 2
• Resuscitation equipment should always be available when administering IV diltiazem 5
• For severe bradycardia, consider atropine or temporary pacing 5
• Synchronized cardioversion is preferred over medication in hemodynamically unstable patients 5

Common Pitfalls to Avoid

• Do not give diltiazem or verapamil for wide-complex tachycardias unless the arrhythmia is known with certainty to be supraventricular in origin 2
• Avoid routine combination with beta-blockers without careful monitoring 2
• Do not use in patients with heart failure with reduced ejection fraction due to negative inotropic effects 2