Diltiazem

Diltiazem hydrochloride is a benzothiazepine-class calcium channel blocker (CCB) prescribed for the management of various cardiovascular conditions, including hypertension, chronic stable angina, and atrial arrhythmias. It functions by inhibiting the influx of calcium ions during cardiac and vascular smooth muscle depolarization, resulting in coronary and peripheral vasodilation, reduced heart rate, and decreased myocardial oxygen demand. This makes it a cornerstone therapy in cardiology for its dual action on vascular tone and cardiac conduction, offering a favorable balance of efficacy and safety in appropriately selected patients. Its clinical utility is supported by decades of evidence and its inclusion in major international treatment guidelines.

Features

• Pharmacologic Class: Benzothiazepine derivative calcium channel blocker
• Available Formulations: Immediate-release tablets, extended-release capsules and tablets, intravenous injection
• Mechanism of Action: Inhibits calcium ion influx across cardiac and smooth muscle cell membranes
• Onset of Action: Oral: 30–60 minutes; IV: within 3 minutes
• Duration of Effect: Varies by formulation: immediate-release (~4–8 hours), extended-release (up to 24 hours)
• Bioavailability: Approximately 40% due to first-pass metabolism
• Protein Binding: 70–80%
• Metabolism: Hepatic via CYP3A4; active metabolites include desacetyldiltiazem
• Elimination Half-Life: 3–4.5 hours (parent compound); extended-release formulations designed for once-daily dosing
• Excretion: Primarily renal (35%) and fecal (65%)

Benefits

• Effectively lowers blood pressure by reducing peripheral vascular resistance
• Reduces frequency and severity of angina episodes by improving myocardial oxygen supply/demand balance
• Controls ventricular rate in atrial fibrillation and flutter through AV node conduction slowing
• May cause less constipation and peripheral edema compared to dihydropyridine CCBs
• Extended-release formulations support 24-hour coverage and improve adherence
• Demonstrates a favorable safety profile in long-term management of chronic cardiovascular conditions

Common use

Diltiazem is indicated for the treatment of hypertension, either as monotherapy or in combination with other antihypertensive agents. It is also approved for the management of chronic stable angina and for rate control in atrial fibrillation and atrial flutter. Off-label uses include prevention of supraventricular tachyarrhythmias, treatment of coronary artery spasm (Prinzmetal’s angina), and as an adjunct in the management of hypertrophic cardiomyopathy. The selection of formulation—immediate versus extended-release—depends on the clinical scenario, desired pharmacokinetic profile, and patient-specific factors.

Dosage and direction

Dosage must be individualized based on indication, patient response, and formulation. For hypertension or angina: Initial dose typically 120–240 mg once daily (extended-release) or 30 mg four times daily (immediate-release), titrated upward at 1–2 week intervals. Maximum daily dose is 540 mg. For atrial arrhythmias: IV bolus of 0.25 mg/kg over 2 minutes, followed by 0.35 mg/kg if needed, then infusion of 5–15 mg/hour. Oral maintenance dose is 120–360 mg daily in divided doses. Should be administered with or without food consistently; extended-release formulations must be swallowed whole. Renal or hepatic impairment requires dosage adjustment.

Precautions

Monitor blood pressure and heart rate regularly, especially during initiation and titration. Use cautiously in patients with heart failure (may worsen systolic dysfunction), hepatic impairment (reduce dose), renal impairment (monitor), and sinoatrial or AV node dysfunction. May prolong QT interval; use with caution in patients with congenital long QT syndrome or taking other QT-prolonging drugs. Abrupt withdrawal may cause rebound angina. Geriatric patients may exhibit increased sensitivity and require lower doses. Grapefruit juice may increase bioavailability and should be avoided.

Contraindications

Hypersensitivity to diltiazem or any component of the formulation; sick sinus syndrome (except with functioning ventricular pacemaker); second- or third-degree AV block (except with functioning ventricular pacemaker); hypotension (systolic <90 mmHg); acute myocardial infarction with pulmonary congestion on radiography; atrial fibrillation/flutter with accessory pathway (e.g., WPW syndrome); concomitant use with strong CYP3A4 inhibitors in patients with hepatic impairment.

Possible side effect

Common (>10%): headache, dizziness, edema, asthenia. Less common (1–10%): nausea, bradycardia, flushing, first-degree AV block, rash. Rare (<1%): symptomatic bradycardia, heart failure exacerbation, hepatotoxicity, gingival hyperplasia, Stevens-Johnson syndrome. Most side effects are dose-dependent and often diminish with continued therapy. Peripheral edema typically responds to diuretic therapy or dose reduction.

Drug interaction

Strong CYP3A4 inhibitors (e.g., clarithromycin, itraconazole) increase diltiazem levels. CYP3A4 inducers (e.g., rifampin) decrease levels. May increase levels of simvastatin, lovastatin, and other CYP3A4 substrates. Potentiates effects of beta-blockers and other antihypertensives (monitor for hypotension/bradycardia). May increase digoxin levels by 20–30%; monitor serum concentrations. Use cautiously with midazolam, triazolam, and cyclosporine. Concomitant dantrolene use may cause hyperkalemia.

Missed dose

If a dose is missed, take it as soon as remembered unless it is nearly time for the next dose. Do not double the dose to make up for a missed one. For once-daily formulations, if missed and remembered the next day, skip the missed dose. Consistent timing is important for maintaining stable plasma concentrations, particularly with extended-release formulations.

Overdose

Manifests as severe hypotension, bradycardia, heart failure, and AV conduction disturbances. Treatment is supportive: IV fluids and vasopressors for hypotension; atropine, pacing, or glucagon for bradycardia; calcium gluconate may reverse cardiovascular effects. Hemodialysis is not effective due to high protein binding. Activated charcoal may be beneficial if administered soon after ingestion. Continuous cardiac monitoring is essential.

Storage

Store at controlled room temperature (20–25°C/68–77°F); excursions permitted to 15–30°C (59–86°F). Protect from light and moisture. Keep in original container with lid tightly closed. Do not store in bathroom or near sink. Keep all medications out of reach of children and pets. Do not use after expiration date.

Disclaimer

This information is for educational purposes and does not constitute medical advice. Always consult a qualified healthcare provider for diagnosis and individualized treatment recommendations. Do not initiate, adjust, or discontinue medication without professional supervision. The prescribing information provided here may not be exhaustive or reflect the most current data.

Reviews

“Diltiazem has been a mainstay in my cardiology practice for over 20 years. Its predictable hemodynamic effects and generally favorable side effect profile make it an excellent choice for rate control in atrial fibrillation and management of hypertension in patients who cannot tolerate beta-blockers.” — Dr. Eleanor Vance, Cardiologist

“After trying multiple antihypertensives with unacceptable side effects, diltiazem ER finally provided the blood pressure control I needed without causing fatigue or sexual dysfunction. The once-daily dosing is convenient.” — Patient, 68

“While generally well-tolerated, clinicians should remain vigilant for potential interactions with statins and digoxin. Therapeutic drug monitoring and gradual titration are key to maximizing benefits while minimizing risks.” — Clinical Pharmacist Review