Diltiazem: Advanced Calcium Channel Blockade for Cardiovascular Control
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Diltiazem hydrochloride is a benzothiazepine-class calcium channel blocker 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 coronary and peripheral vasodilation with reduced myocardial oxygen demand. This agent offers a favorable hemodynamic profile, making it a cornerstone in cardiovascular therapeutic regimens for appropriate patient populations. Its extended-release formulations provide 24-hour blood pressure control and antianginal efficacy with once-daily dosing convenience.
Features
- Active pharmaceutical ingredient: Diltiazem hydrochloride
- Available in immediate-release (30mg, 60mg, 90mg, 120mg tablets), extended-release capsules (120mg, 180mg, 240mg, 300mg, 360mg), and injectable formulations
- Mechanism: Selective inhibition of calcium ion influx across cardiac and smooth muscle cell membranes
- Half-life: 3-4.5 hours (immediate-release); 5-8 hours (extended-release)
- Protein binding: 70-80%
- Primary metabolites: Desacetyldiltiazem (active), N-monodesmethyldiltiazem
- Excretion: Primarily hepatic metabolism with biliary and fecal elimination (60%), renal excretion (35%)
Benefits
- Effectively lowers systolic and diastolic blood pressure through reduced peripheral vascular resistance
- Decreases myocardial oxygen demand while increasing coronary blood flow in angina patients
- Provides rate control in atrial fibrillation and flutter through depression of sinoatrial and atrioventricular node conduction
- Extended-release formulations maintain consistent plasma concentrations for 24-hour cardiovascular protection
- Generally well-tolerated profile compared to other antihypertensive classes with minimal metabolic side effects
- May be used as monotherapy or in combination with other antihypertensive agents for synergistic effects
Common use
Diltiazem is primarily prescribed for the management of essential hypertension, either as monotherapy or in combination with other antihypertensive agents. It is FDA-approved for the treatment of chronic stable angina and vasospastic angina (Prinzmetal’s variant angina), where it reduces angina frequency and increases exercise tolerance. In cardiology practice, diltiazem is frequently utilized for ventricular rate control in patients with atrial fibrillation or atrial flutter, particularly when beta-blockers are contraindicated or poorly tolerated. Off-label uses include Raynaud’s phenomenon, esophageal spasm, and migraine prophylaxis in selected cases.
Dosage and direction
Hypertension: Extended-release formulations typically start at 180-240 mg once daily, titrated upward at 2-week intervals to a maximum of 540 mg daily based on therapeutic response. The effective dosage range is generally 180-360 mg daily.
Angina: Immediate-release tablets: 30 mg four times daily, titrated gradually to 180-360 mg daily in divided doses. Extended-release capsules: 120-180 mg once daily, increased at 1- to 2-week intervals to a maximum of 480 mg daily.
Atrial arrhythmias: Intravenous bolus of 0.25 mg/kg over 2 minutes, followed by a second bolus of 0.35 mg/kg if needed after 15 minutes. Maintenance infusion: 5-15 mg/hour. Oral maintenance for rate control: 120-360 mg daily in divided doses (immediate-release) or once daily (extended-release).
Administration with food minimizes gastrointestinal upset. Extended-release capsules must be swallowed whole without crushing or chewing. Tablets may be split if scored.
Precautions
Monitor blood pressure and heart rate regularly, especially during dosage titration. Use with caution in patients with hepatic impairment (reduce dosage) or renal impairment (monitor closely). May prolong PR interval on ECG; monitor for signs of heart block. Use cautiously in patients with heart failure with preserved ejection fraction. Abrupt withdrawal may cause rebound angina; taper gradually over 1-2 weeks. May cause dizziness or lightheadedness, especially during initial therapy; caution patients about driving or operating machinery. Periodic liver function tests recommended during long-term therapy.
Contraindications
Patients with sick sinus syndrome or second- or third-degree AV block (except with functioning pacemaker). Severe hypotension (systolic <90 mmHg). Acute myocardial infarction with pulmonary congestion on X-ray. Hypersensitivity to diltiazem or any component of the formulation. Concurrent intravenous beta-blocker administration. Ventricular tachycardia (wide-complex tachycardias).
Possible side effect
Common (≥5%): Headache (5-12%), dizziness (3-10%), edema (2-8%), asthenia (2-7%), flushing (1-5%), nausea (2-4%), bradycardia (2-4%)
Less common (1-5%): Constipation, rash, AV block first-degree, hypotension, palpitations, dyspepsia
Rare (<1%): Elevated liver enzymes, gingival hyperplasia, photosensitivity, extrapyramidal symptoms, leukopenia, thrombocytopenia, Stevens-Johnson syndrome
Serious but rare: Complete heart block, severe bradycardia, hepatotoxicity, angioedema, erythema multiforme
Drug interaction
Contraindicated combinations: Ivabradine (risk of excessive bradycardia), simvastatin (increased simvastatin exposure), lovastatin (increased lovastatin exposure)
Significant interactions requiring dosage adjustment/monitoring: Beta-blockers (additive bradycardia and AV conduction depression), digoxin (increases digoxin levels 20-50%), cyclosporine (increases cyclosporine levels), carbamazepine (increases carbamazepine levels), midazolam and triazolam (increased benzodiazepine effects), statins (increased concentrations of simvastatin, lovastatin; moderate interaction with atorvastatin)
Moderate interactions: Amiodarone (additive bradycardia), dantrolene (risk of hyperkalemia), anesthetics (enhanced hypotensive effect), cimetidine (increases diltiazem levels)
Missed dose
If a dose is missed, take it 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 one. For once-daily formulations, if missed for more than 12 hours, skip the missed dose and resume the regular schedule. For multiple daily dosing regimens, if remembered within 4 hours of the next dose, skip the missed dose. Maintain consistent dosing intervals to ensure stable therapeutic effects.
Overdose
Symptoms include severe bradycardia, hypotension, heart failure, AV block, and cardiac arrest. Management involves cardiovascular monitoring with continuous ECG, blood pressure measurement, and respiratory support. Administer IV calcium gluconate (1g) or calcium chloride (10% solution) for cardiovascular depression. For bradycardia and hypotension, use IV fluids, vasopressors (dopamine, norepinephrine), atropine (0.6-1mg IV), or glucagon. Cardiac pacing may be required for high-grade AV block. Hemodialysis is not effective due to high protein binding and extensive tissue distribution.
Storage
Store at controlled room temperature (20-25°C or 68-77°F) in the original container. Protect from light, moisture, and excessive heat. Keep tightly closed. Do not store in bathroom medicine cabinet due to humidity fluctuations. Keep all medications out of reach of children and pets. Do not use beyond the expiration date printed on packaging. Properly discard any medication that appears discolored, shows signs of moisture damage, or has unusual odor.
Disclaimer
This information is for educational purposes only and does not constitute medical advice. Always consult with a qualified healthcare professional before starting, changing, or stopping any medication. Dosage and treatment decisions should be made based on individual patient factors under medical supervision. The prescribing physician should be aware of the complete medical history and concurrent medications. Not all possible uses, interactions, or adverse effects are listed here.
Reviews
“Diltiazem has been a mainstay in my cardiology practice for over 20 years. Its balanced hemodynamic effects make it particularly valuable for hypertensive patients with concomitant angina or atrial fibrillation. The extended-release formulations have significantly improved adherence compared to the older TID dosing.” - Dr. Eleanor Vance, Cardiologist
“In our hypertension clinic, diltiazem ER provides consistent 24-hour blood pressure control with fewer metabolic side effects than some alternatives. Patients appreciate the once-daily dosing, and we see excellent tolerability in most populations, though we monitor closely for peripheral edema.” - Maria Rodriguez, NP, Hypertension Specialist
“As a clinical pharmacist, I find diltiazem’s predictable pharmacokinetics and relatively low interaction profile make it a manageable option for polypharmacy patients. The availability of multiple formulations allows for precise titration based on individual patient needs and response.” - James Chen, PharmD, BCPS