Diltiazem hydrochloride is a benzothiazepine-class calcium channel blocker (CCB) prescribed for the management of various cardiovascular conditions. It functions by inhibiting the influx of calcium ions during cardiac and vascular smooth muscle depolarization, leading to reduced myocardial contractility, slowed sinoatrial and atrioventricular nodal conduction, and coronary and systemic arterial vasodilation. This multifaceted pharmacodynamic profile makes it a cornerstone therapy in hypertension, chronic stable angina, and certain arrhythmias, offering a favorable balance between efficacy and tolerability for a broad patient demographic.

Features

• Pharmacologic Class: Benzothiazepine derivative calcium channel blocker.
• Mechanism of Action: Inhibits transmembrane influx of calcium ions into cardiac muscle and vascular smooth muscle cells.
• Hemodynamic Effects: Reduces peripheral vascular resistance and afterload; decreases heart rate and myocardial oxygen demand.
• Bioavailability: Approximately 40% due to significant first-pass metabolism.
• Protein Binding: 70–80%.
• Half-Life: Biphasic; initial phase 1.5–3.5 hours, terminal elimination phase 5–8 hours. Extended-release formulations have prolonged profiles.
• Metabolism: Primarily hepatic via cytochrome P450 isoenzyme CYP3A4; extensive deacetylation and demethylation.
• Excretion: Primarily in urine (2–4% as unchanged drug) and feces.
• Available Formulations: Immediate-release tablets, extended-release capsules (once-daily), and intravenous formulation.

Benefits

• Provides effective blood pressure control by reducing systemic vascular resistance, thereby lowering the long-term risk of stroke, myocardial infarction, and kidney damage.
• Manages chronic stable angina by decreasing myocardial oxygen demand through reductions in heart rate and contractility, and by increasing oxygen supply via coronary vasodilation.
• Controls heart rate in patients with atrial fibrillation or atrial flutter by prolonging AV nodal refractory period and slowing conduction.
• Offers a generally favorable side effect profile compared to other antianginal and antihypertensive agents, with a lower incidence of constipation than verapamil and less reflex tachycardia than dihydropyridines.
• Available in extended-release formulations that support 24-hour efficacy with once-daily dosing, improving patient adherence and providing smooth, consistent plasma levels.

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 (effort-associated angina) and for rate control in patients with atrial fibrillation or atrial flutter. Off-label uses may include the treatment of supraventricular tachycardias (e.g., AV nodal reentrant tachycardia), Raynaud’s phenomenon, and as part of a multifaceted approach to coronary artery disease management.

Dosage and direction

Dosage is highly individualized based on indication, patient response, and formulation. For hypertension or angina using immediate-release tablets, the typical initial adult dose is 30 mg four times daily, titrated upward to 180–360 mg per day in divided doses. For extended-release capsules, the initial dose is often 120–180 mg once daily, which may be increased to 240–360 mg once daily. For atrial arrhythmias, intravenous diltiazem may be administered as an initial bolus of 0.25 mg/kg over 2 minutes, followed by a second bolus of 0.35 mg/kg if needed, and a continuous infusion of 5–15 mg/hour. Tablets should be swallowed whole, with or without food; extended-release capsules must not be crushed, chewed, or opened. Dosage adjustments are mandatory in patients with hepatic impairment.

Precautions

Patients should be monitored for signs of bradycardia, AV block, or heart failure. Liver function tests should be performed periodically, as the drug is extensively metabolized by the liver. Diltiazem can occasionally cause symptomatic hypotension. It should be used with caution in patients with impaired renal function, although it is less dependent on renal excretion than other classes. Abrupt withdrawal may cause rebound angina in patients with coronary artery disease; dosage should be tapered under medical supervision. Patients should be advised about the potential for dizziness, especially during the initiation of therapy.

Contraindications

Diltiazem is contraindicated in patients with sick sinus syndrome or second- or third-degree AV block (except in the presence of a functioning ventricular pacemaker), patients with severe hypotension (systolic pressure < 90 mm Hg), those with acute myocardial infarction and pulmonary congestion documented by x-ray on admission, and patients with known hypersensitivity to diltiazem or any component of the formulation. The intravenous form is contraindicated in patients with atrial fibrillation/flutter associated with an accessory bypass tract (e.g., Wolff-Parkinson-White syndrome).

Possible side effect

Common side effects (often dose-related and may diminish with continued use) include dizziness (3.6%), headache (3.3%), edema (3.0%), asthenia (2.6%), first-degree AV block (2.4%), bradycardia (2.2%), flushing (1.8%), and nausea (1.8%). Less common but more serious adverse reactions include symptomatic hypotension, heart failure or pulmonary edema, severe bradycardia, syncope, second- or third-degree AV block, and elevated liver enzymes (AST, ALT) and alkaline phosphatase. Rash is an uncommon occurrence.

Drug interaction

Diltiazem is a moderate inhibitor of CYP3A4 and is itself a substrate of this enzyme, leading to numerous potential interactions. Coadministration with beta-blockers or digoxin can potentiate bradycardia and AV block. It can significantly increase serum concentrations of simvastatin, lovastatin, cyclosporine, sirolimus, tacrolimus, and many benzodiazepines. Concomitant use with other antihypertensive agents can lead to additive hypotensive effects. CYP3A4 inducers like rifampin, carbamazepine, and St. John’s Wort can markedly reduce diltiazem plasma levels, diminishing its efficacy. Grapefruit juice can inhibit diltiazem metabolism and increase its bioavailability.

Missed dose

If a dose of the immediate-release formulation is missed, it should be taken as soon as possible. However, if it is almost time for the next dose, the missed dose should be skipped and the regular dosing schedule resumed. Double doses should not be taken. For a once-daily extended-release formulation, the missed dose should be taken as soon as remembered on the same day. If remembered the next day, the missed dose should be skipped. The capsule should not be opened to make up a partial dose.

Overdose

Overdose can lead to severe hypotension, bradycardia, heart failure, and cardiac arrest due to the drug’s cardiovascular effects. Specific supportive measures should be initiated, including continuous ECG and blood pressure monitoring. Treatment is primarily supportive and may include IV fluids and vasopressors (e.g., dopamine or norepinephrine) for hypotension, atropine for bradycardia, and IV calcium gluconate. Cardiac pacing may be required for high-grade AV block. Due to extensive protein binding and a large volume of distribution, diltiazem is not dialyzable.

Storage

Store at controlled room temperature, 20°–25°C (68°–77°F), in a tight, light-resistant container. Keep all medications out of the reach of children and pets. Do not use after the expiration date printed on the container. Do not store in damp places, such as bathrooms.

Disclaimer

This information is for educational and informational purposes only and does not constitute medical advice. It is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication. Never disregard professional medical advice or delay in seeking it because of something you have read here. The author and publisher are not responsible for any specific health or allergy needs that may require medical supervision and are not liable for any damages or negative consequences from any treatment, action, application, or preparation, to any person reading or following the information in this document.

Reviews

“Diltiazem has been a mainstay in my cardiology practice for over two decades. Its dual action of vasodilation and heart rate control makes it exceptionally useful for patients with concomitant hypertension and angina. The extended-release formulations have significantly improved adherence and 24-hour blood pressure control in my patient population.” – Dr. Eleanor Vance, MD, Cardiologist.

“As a clinical pharmacist, I appreciate diltiazem’s predictable pharmacokinetics and well-documented interaction profile. While CYP3A4 interactions require vigilance, they are manageable with careful monitoring and dose adjustment. It remains a versatile and effective option within the CCB class.” – Michael Sorenson, PharmD, BCPS.

“After being switched to diltiazem ER from a different medication, my blood pressure has been consistently controlled without the ankle swelling I experienced before. The once-daily dosing is convenient and easy to remember.” – Patient, 68-year-old male with hypertension.