Diltiazem is a benzothiazepine-class calcium channel blocker (CCB) prescribed for the management of hypertension, chronic stable angina, and certain arrhythmias. It functions by inhibiting the influx of calcium ions during cardiac and vascular smooth muscle depolarization, leading to reduced peripheral vascular resistance, decreased myocardial oxygen demand, and modulation of sinoatrial and atrioventricular nodal conduction. This comprehensive profile details its pharmacological characteristics, therapeutic applications, and essential safety information for healthcare professionals and informed patients.

Features

• Pharmacologic Class: Benzothiazepine derivative calcium channel blocker
• Mechanism of Action: Inhibits transmembrane influx of calcium ions into cardiac and vascular smooth muscle
• Available Formulations: Immediate-release tablets, extended-release capsules and tablets, intravenous injection
• Bioavailability: Approximately 40% due to first-pass metabolism
• Protein Binding: 70-80%
• Metabolism: Extensive hepatic metabolism via cytochrome P450 3A4 (CYP3A4)
• Elimination Half-life: 3-4.5 hours (immediate-release); 5-8 hours (extended-release)
• Excretion: Primarily renal (35%) and fecal (65%)

Benefits

• Effectively lowers blood pressure through vasodilation of peripheral arteries
• Reduces frequency and severity of angina episodes by decreasing myocardial oxygen demand
• Controls ventricular rate in atrial fibrillation and flutter through AV node conduction slowing
• Demonstrates favorable safety profile compared to other antiarrhythmic agents
• Extended-release formulations provide 24-hour coverage with once-daily dosing
• May be used as monotherapy or in combination with other antihypertensive agents

Common use

Diltiazem is indicated for the treatment of essential hypertension, either as monotherapy or in combination with other antihypertensive agents. It is approved for the management of chronic stable angina and for rate control in atrial fibrillation and flutter. The medication may also be used off-label for certain other supraventricular tachyarrhythmias, Raynaud’s phenomenon, and as adjunctive therapy in hypertrophic cardiomyopathy. Clinical studies have demonstrated its efficacy in reducing both systolic and diastolic blood pressure while maintaining coronary blood flow.

Dosage and direction

Dosage must be individualized based on therapeutic response and tolerance. For hypertension: Initial dose typically 180-240 mg once daily (extended-release), titrated to a maximum of 540 mg daily. For angina: Initial dose 120-180 mg once daily (extended-release), maximum 540 mg daily. For atrial fibrillation: Oral loading dose strategies may be employed under medical supervision. Immediate-release formulations are usually administered three to four times daily. Tablets should be swallowed whole and not crushed or chewed. Administration with food may minimize gastrointestinal upset. Regular monitoring of blood pressure, heart rate, and clinical response is essential during dosage titration.

Precautions

Patients should be monitored for signs of hypotension, particularly during initial titration or when adding other antihypertensive agents. Caution is advised in patients with heart failure or significantly impaired ventricular function due to potential negative inotropic effects. Hepatic impairment requires dosage adjustment as metabolism is primarily hepatic. Renal impairment necessitates careful monitoring, though dosage adjustment is generally not required until significant impairment (CrCl <30 mL/min) is present. Elderly patients may experience increased sensitivity and require lower initial doses. Abrupt discontinuation should be avoided due to potential rebound hypertension or angina exacerbation.

Contraindications

Diltiazem is contraindicated in patients with sick sinus syndrome or second- or third-degree AV block (except with functioning ventricular pacemaker), hypotension (systolic pressure <90 mmHg), acute myocardial infarction with pulmonary congestion, hypersensitivity to diltiazem or any component of the formulation, and patients with atrial fibrillation/flutter associated with accessory bypass tracts (e.g., WPW syndrome). The intravenous formulation is additionally contraindicated in ventricular tachycardia.

Possible side effect

Common adverse reactions include headache (5-12%), dizziness (3-10%), edema (2-8%), asthenia (2-7%), and first-degree AV block (2-8%). Less frequent effects include flushing, nausea, rash, and bradycardia. Serious but rare adverse events include symptomatic hypotension, heart failure exacerbation, hepatotoxicity, and severe bradyarrhythmias. Dermatological reactions ranging from erythema multiforme to toxic epidermal necrolysis have been reported. Laboratory abnormalities may include transient elevations in liver enzymes and, rarely, leukopenia.

Drug interaction

Diltiazem is a moderate CYP3A4 inhibitor and substrate, resulting in numerous potential interactions. Coadministration with beta-blockers may produce additive effects on cardiac conduction and contractility. Concurrent use with digoxin increases digoxin concentrations by 20-50%. Simvastatin and lovastatin concentrations may increase significantly. Diltiazem may increase concentrations of cyclosporine, sirolimus, tacrolimus, and many benzodiazepines. Potent CYP3A4 inhibitors (ketoconazole, clarithromycin) increase diltiazem concentrations. Inducers (rifampin, phenytoin) decrease diltiazem efficacy. Grapefruit juice may increase bioavailability.

Missed dose

If a dose is missed, it should be taken as soon as remembered unless it is nearly time for the next scheduled dose. In that case, the missed dose should be skipped and the regular dosing schedule resumed. Patients should not double the dose to make up for a missed one. For extended-release formulations, maintaining consistent dosing intervals is particularly important for stable therapeutic effects. Healthcare providers should educate patients about the importance of adherence while providing specific guidance for their particular formulation and dosing schedule.

Overdose

Manifestations of overdose include severe hypotension, bradycardia, heart failure, and conduction abnormalities. Management involves cardiovascular monitoring and supportive care. Activated charcoal may be beneficial if administered promptly. Bradycardia may respond to atropine, isoproterenol, or cardiac pacing. Hypotension may require vasopressors such as dopamine or norepinephrine. Calcium gluconate administration (1 g IV) may reverse some cardiovascular effects. Hemodialysis is not effective due to extensive protein binding and large volume of distribution. Consultation with a poison control center is recommended.

Storage

Store at controlled room temperature (20-25°C or 68-77°F), protecting from moisture and light. Keep in the original container with the lid tightly closed. Do not store in bathroom areas where moisture levels fluctuate. Keep all medications out of reach of children and pets. Do not use beyond the expiration date printed on the packaging. Properly dispose of unused medication through medication take-back programs or according to FDA guidelines if no program is available.

Disclaimer

This information is provided for educational purposes only and does not constitute medical advice. Individual therapeutic decisions should be made by qualified healthcare professionals based on comprehensive patient assessment. The prescribing physician should be consulted for specific dosage recommendations and management of adverse effects. Patients should not alter their medication regimen without medical supervision. While every effort has been made to ensure accuracy, medical knowledge evolves and the most current prescribing information should always be consulted.

Reviews

Clinical trials consistently demonstrate diltiazem’s efficacy in hypertension management with response rates of 60-70% as monotherapy. Angina studies show significant reduction in attack frequency and nitrate consumption. In atrial fibrillation, successful rate control is achieved in approximately 80% of patients. The extended-release formulations are particularly praised for improved adherence and stable 24-hour coverage. Most reviews note favorable tolerability compared to other antihypertensive classes, though edema remains a common reason for discontinuation. The predictable pharmacokinetics and well-characterized drug interaction profile make it a preferred option in many clinical scenarios.