Diltiazem hydrochloride is a benzothiazepine derivative calcium channel blocker (CCB) indicated for the management of 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 reduced peripheral vascular resistance, decreased myocardial oxygen demand, and modulation of sinoatrial and atrioventricular nodal conduction. This comprehensive profile details its pharmacological characteristics, clinical applications, and essential safety information for healthcare professionals.

Features

• Pharmacologic Class: Benzothiazepine calcium channel blocker
• Chemical Name: (2S,3S)-5-[2-(Dimethylamino)ethyl]-2,3-dihydro-2-(4-methoxyphenyl)-4,1-benzothiazepin-3-ol acetate
• Available Formulations: Immediate-release tablets, extended-release capsules (once-daily and twice-daily formulations), and intravenous injection
• Mechanism of Action: Selective inhibition of L-type calcium channels in vascular smooth muscle and cardiac cells
• Bioavailability: Approximately 40% (subject to first-pass metabolism)
• Protein Binding: 70–80%
• Metabolism: Hepatic via CYP3A4 isoenzyme
• Elimination Half-Life: 3–4.5 hours (immediate-release); extended-release formulations designed for 24-hour coverage
• Excretion: Primarily renal (35%) and fecal (65%)

Benefits

• Provides effective reduction of systolic and diastolic blood pressure through arteriolar vasodilation
• Decreases frequency and severity of angina pectoris episodes by reducing myocardial oxygen demand
• Controls ventricular rate in atrial fibrillation and flutter through AV nodal conduction slowing
• Offers multiple formulation options for tailored therapeutic regimens across cardiovascular indications
• Demonstrates favorable safety profile compared to non-dihydropyridine calcium channel blockers
• May be used as monotherapy or in combination with other antihypertensive agents

Common use

Diltiazem is primarily prescribed for the management of essential hypertension, either as monotherapy or in combination with other antihypertensive agents. It is equally effective in treating chronic stable angina by reducing coronary vascular resistance and increasing coronary blood flow. The intravenous formulation is specifically indicated for rapid control of ventricular rate in atrial fibrillation or flutter, as well as for termination of paroxysmal supraventricular tachycardia. Off-label uses include Raynaud’s phenomenon, esophageal spasm, and migraine prophylaxis, though evidence for these indications varies.

Dosage and direction

Dosage must be individualized based on indication, patient response, and formulation. For hypertension: Initial dose typically ranges from 180–240 mg once daily with extended-release formulations, titrated upward at 2-week intervals to maximum 540 mg daily. For angina: Initial dose 120–180 mg once daily, maximum 480 mg daily. For atrial arrhythmias: Intravenous bolus of 0.25 mg/kg over 2 minutes, followed by 0.35 mg/kg if needed, then continuous infusion of 5–15 mg/hour. Oral maintenance for rate control typically begins at 120–360 mg daily in divided doses. All formulations should be administered consistently with regard to meals. Extended-release capsules must be swallowed whole; do not crush, chew, or divide.

Precautions

Monitor blood pressure and heart rate regularly, especially during initiation and titration. Use caution in patients with hepatic impairment (reduce dosage) or renal impairment (monitor closely). May prolong AV conduction times; periodic ECG monitoring recommended. Gradual withdrawal is advised to avoid rebound angina. May cause symptomatic hypotension; advise patients against rapid position changes. Use with caution in patients with congestive heart failure with impaired ventricular function. Not recommended during pregnancy unless potential benefit justifies potential risk to fetus. Breastfeeding should be discontinued during therapy.

Contraindications

Patients with sick sinus syndrome or second- or third-degree AV block (except with functioning pacemaker). Severe hypotension (systolic pressure <90 mmHg). Acute myocardial infarction with pulmonary congestion on X-ray. Hypersensitivity to diltiazem or any component of the formulation. Concurrent use with strong CYP3A4 inhibitors in patients with hepatic impairment. Intravenous administration contraindicated in patients with atrial fibrillation/flutter associated with accessory pathways (e.g., WPW syndrome).

Possible side effect

Most common adverse reactions (>5%) include headache, dizziness, edema, asthenia, and first-degree AV block. Less frequent effects (1–5%): Bradycardia, flushing, nausea, rash, elevated liver enzymes. Rare but serious: Symptomatic hypotension, heart failure exacerbation, severe bradycardia, hepatotoxicity, 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 (ketoconazole, clarithromycin, ritonavir) may significantly increase diltiazem concentrations. May increase levels of CYP3A4 substrates (simvastatin, lovastatin, cyclosporine). Additive effects with other antihypertensives, beta-blockers, and digitalis. May increase digoxin levels by 20–40%; monitor digoxin concentrations. Cimetidine increases diltiazem bioavailability. Carbamazepine, phenytoin, and rifampin may decrease diltiazem efficacy. Anesthetics may potentiate cardiovascular effects. Grapefruit juice may increase bioavailability.

Missed dose

If a dose is missed, it should be taken as soon as remembered unless it is almost time for the next scheduled dose. Do not double the dose to make up for a missed dose. For once-daily formulations: If missed, take within 12 hours of missed dose; otherwise skip and resume regular schedule. For multiple daily dosing: Take missed dose if within 4 hours of scheduled time. Patients should not discontinue therapy abruptly without medical supervision.

Overdose

Symptoms include severe bradycardia, heart failure, hypotension, and conduction disturbances. Management includes gastric lavage if recent ingestion, activated charcoal, and supportive care. Specific antidotes: Intravenous calcium gluconate (1 g) may reverse hemodynamic effects. Atropine (0.6–1 mg IV) for bradycardia. Isoproterenol or cardiac pacing may be required for refractory bradycardia. Dopamine or norepinephrine for hypotension. Hemodialysis is not effective due to high protein binding.

Storage

Store at controlled room temperature (20–25°C or 68–77°F). Protect from light and moisture. Keep in original container with lid tightly closed. Do not store in bathroom or near kitchen sink. Keep all medications out of reach of children and pets. Do not use after expiration date printed on packaging. Do not freeze liquid formulations.

Disclaimer

This information is intended for healthcare professionals and should not replace professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read in this document. Actual prescribing should be based on comprehensive patient assessment and current prescribing guidelines.

Reviews

Clinical studies demonstrate diltiazem’s efficacy in reducing blood pressure by 10-15 mmHg systolic and 8-10 mmHg diastolic in hypertensive patients. Angina frequency reduction of 50-70% has been observed in stable angina trials. For rate control in atrial fibrillation, intravenous diltiazem achieves ventricular rate <100 bpm within 30 minutes in 85-95% of patients. Meta-analyses show comparable efficacy to beta-blockers and other calcium channel blockers with generally favorable tolerability. Long-term studies confirm maintained efficacy with continued therapy and low incidence of tolerance development.