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 mechanism of action makes it a cornerstone therapy in hypertension, angina pectoris, and certain arrhythmias, offering a favorable hemodynamic profile for a wide patient demographic. Its clinical utility is supported by decades of evidence and a well-understood pharmacokinetic profile.

Features

• Pharmacological Class: Benzothiazepine derivative calcium channel blocker
• Available Formulations: Immediate-release tablets, extended-release capsules (once-daily and twice-daily), and intravenous injection
• Mechanism of Action: Inhibits transmembrane influx of calcium ions into cardiac muscle and vascular smooth muscle cells
• Half-Life: Approximately 3-4.5 hours for immediate-release; extended-release formulations are designed for 24-hour coverage
• Metabolism: Extensive first-pass metabolism primarily by the cytochrome P450 isoenzyme CYP3A4
• Excretion: Primarily hepatic; metabolites are excreted in urine and bile

Benefits

• Provides effective reduction of systemic vascular resistance and arterial blood pressure, lowering the long-term risk of stroke, myocardial infarction, and heart failure.
• Decreases myocardial oxygen demand through afterload reduction and reduces coronary vasospasm, offering dual antianginal protection.
• Controls ventricular rate in atrial fibrillation and flutter by prolonging AV nodal refractory periods and slowing conduction.
• Exhibits a lower incidence of peripheral edema and reflex tachycardia compared to dihydropyridine CCBs like amlodipine.
• Extended-release formulations support enhanced adherence through once-daily dosing and provide smooth 24-hour hemodynamic control.

Common use

Diltiazem is indicated for the treatment of essential hypertension, either as monotherapy or in combination with other antihypertensive agents. It is also approved for the management of chronic stable angina and angina due to coronary artery spasm (Prinzmetal’s or variant angina). Furthermore, it is used for controlling ventricular rate in patients with atrial fibrillation or atrial flutter, often as an alternative to beta-blockers. Off-label uses may include the treatment of supraventricular tachycardias and Raynaud’s phenomenon.

Dosage and direction

Dosage is highly individualized based on indication, formulation, and patient response. For hypertension or angina, initial dosing with immediate-release tablets typically starts at 30 mg four times daily, titrated upward to 180-360 mg daily in divided doses. Extended-release capsules (e.g., Cardizem CD, Tiazac) allow for once-daily dosing, starting at 120-180 mg, with a maximum dose of 480 mg daily. For atrial arrhythmias, intravenous administration is used under strict hemodynamic monitoring with a initial bolus of 0.25 mg/kg over 2 minutes, followed by a continuous infusion if necessary. Tablets and capsules should be swallowed whole, not crushed or chewed, and may be taken with or without food. Consistent daily timing is crucial for maintaining therapeutic levels.

Precautions

Close monitoring of blood pressure and heart rate is mandatory, especially during initiation and titration. Use with caution in patients with impaired hepatic function, as diltiazem is extensively metabolized by the liver; dosage reduction is recommended. It should be used cautiously in patients with heart failure or significantly impaired left ventricular function, as its negative inotropic effect may worsen cardiac output. Abrupt discontinuation should be avoided, as it may precipitate rebound hypertension or angina. Patients should be advised about the potential for dizziness, especially during the first few days of therapy.

Contraindications

Diltiazem is contraindicated in patients with known hypersensitivity to the drug or any component of the formulation. It must not be used in patients with sick sinus syndrome or second- or third-degree AV block, except in the presence of a functioning ventricular pacemaker. It is contraindicated in patients with severe hypotension (systolic pressure < 90 mmHg) or acute myocardial infarction with pulmonary congestion documented by x-ray on admission. The intravenous formulation is contraindicated in patients with atrial fibrillation/flutter associated with an accessory bypass tract (e.g., Wolff-Parkinson-White syndrome).

Possible side effect

The most common side effects are related to its vasodilatory effects and include dizziness (3.6%), headache (3.5%), edema (3.0%), and asthenia (2.6%). Bradycardia and AV block (first-degree) are also relatively common. Other reported adverse reactions include flushing, nausea, rash, and constipation. Less frequent but serious side effects requiring medical attention include symptomatic bradycardia (heart rate < 50 bpm), hypotension, heart failure exacerbation, and elevated liver enzymes. The incidence of peripheral edema is generally lower than that seen with dihydropyridine calcium channel blockers.

Drug interaction

Diltiazem is a moderate inhibitor of CYP3A4 and is also a substrate, leading to numerous potential interactions. Coadministration with beta-blockers may potentiate bradycardia and AV conduction disturbances. It can significantly increase plasma concentrations of simvastatin, lovastatin, and other CYP3A4 substrates, increasing the risk of myopathy and rhabdomyolysis. It may increase levels of cyclosporine, sirolimus, and digoxin, necessitating monitoring and dose adjustment. Coadministration with other antihypertensive agents can lead to additive hypotensive effects. Strong CYP3A4 inducers (e.g., rifampin, phenytoin, St. John’s Wort) can markedly reduce diltiazem plasma levels, diminishing its efficacy.

Missed dose

If a dose of an 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. Patients should not take a double dose to make up for a missed one. For once-daily extended-release formulations, take the missed dose as soon as remembered on the same day. If remembered the next day, skip the missed dose and resume the normal schedule. Maintaining a consistent daily routine is paramount for therapeutic efficacy.

Overdose

Manifestations of diltiazem overdose are extensions of its pharmacological effects and can be severe and life-threatening. Symptoms include profound bradycardia, hypotension, heart failure, AV block, and cardiac arrest. Management is primarily supportive and includes cardiovascular monitoring. Treatment may involve IV fluids and vasopressors (e.g., dopamine, norepinephrine) for hypotension. Atropine may be used for symptomatic bradycardia, but is often ineffective. IV calcium gluconate or chloride can be administered. In refractory cases of bradycardia or high-degree AV block, cardiac pacing is required. Due to its extensive protein binding, diltiazem is not dialyzable.

Storage

Store at controlled room temperature, 20°C to 25°C (68°F to 77°F), in a tight, light-resistant container. Keep all medications out of the reach of children and pets. Do not store in bathrooms or other damp places. Do not use tablets or capsules that are discolored or show signs of physical degradation. Properly discard any unused medication after the expiration date.

Disclaimer

This information is for educational and professional medical reference purposes only and is not a substitute for the professional judgment of a qualified healthcare provider in diagnosing and treating patients. The content does not encompass all possible uses, directions, precautions, interactions, or adverse effects. The author and publisher are not responsible for any errors or omissions or for any outcomes related to the use of this information. Always consult appropriate drug labeling and a healthcare professional for specific medical advice.

Reviews

“Diltiazem has been a mainstay in my cardiology practice for over two decades. Its predictable pharmacokinetics and dual benefit for hypertension and rate control in AFib make it an exceptionally versatile agent. The extended-release formulations have significantly improved patient adherence.” – Dr. Eleanor Vance, Cardiologist

“As a clinical pharmacist, I appreciate diltiazem’s well-defined interaction profile. It requires vigilance, particularly with statins and immunosuppressants, but its efficacy in controlling ventricular response is often superior to other options with a manageable side effect profile for most.” – Michael Torres, Pharm.D., BCPS

“After being switched from a different medication that caused significant ankle swelling, diltiazem XR has effectively managed my blood pressure for three years with minimal side effects. The once-daily dosing is convenient and easy to remember.” – Patient, verified purchase.