What are the important consulting points for diltiazem (calcium channel blocker)?

From the Guidelines

Diltiazem should be used with caution and under close monitoring, particularly in patients with heart failure, conduction disorders, or liver impairment, and the dose should be titrated gradually to minimize the risk of adverse effects such as hypotension and bradycardia. When consulting on diltiazem, it is essential to consider its primary uses, including hypertension, angina, and certain arrhythmias like atrial fibrillation. The initial dose should be lower, typically 30mg three or four times daily for immediate-release or 120-240mg once daily for extended-release, and adjusted based on patient response 1. Regular monitoring of blood pressure and heart rate is crucial, as diltiazem can cause hypotension and bradycardia. Patients should be advised to take extended-release formulations whole without crushing or chewing. Important drug interactions include an increased risk of bradycardia with beta-blockers, elevated levels of certain statins, and reduced effectiveness of clopidogrel. Caution patients about potential side effects, including headache, dizziness, constipation, and ankle edema.

Key considerations for the use of diltiazem include:

• Starting with lower doses and titrating gradually based on patient response
• Monitoring blood pressure and heart rate regularly
• Avoiding abrupt discontinuation and instead gradually tapering the dose to prevent rebound angina or hypertension
• Being cautious in patients with heart failure, conduction disorders, or liver impairment
• Considering alternative treatments for arrhythmias, such as beta-blockers or other calcium channel blockers, depending on the specific condition and patient factors 1.

In the context of supraventricular tachycardia, diltiazem can be used for acute rate control in hemodynamically stable patients, with a recommended dose of 15 mg to 20 mg (0.25 mg/kg) IV over 2 minutes, and a maintenance infusion dose of 5 mg/hour to 15 mg/hour, titrated to heart rate 1. However, it is crucial to avoid using diltiazem in patients with pre-excited atrial fibrillation or flutter, as it can accelerate the ventricular response.

Overall, the use of diltiazem requires careful consideration of its benefits and risks, as well as close monitoring and adjustment of the dose to minimize adverse effects and optimize patient outcomes.

From the FDA Drug Label

Patients taking other drugs that are substrates of CYP450 3A4, especially patients with renal and/or hepatic impairment, may require dosage adjustment when starting or stopping concomitantly administered diltiazem in order to maintain optimum therapeutic blood levels Anesthetics: The depression of cardiac contractility, conductivity, and automaticity, as well as the vascular dilation associated with anesthetics, may be potentiated by calcium channel blockers. Benzodiazepines: Studies showed that diltiazem increased the AUC of midazolam and triazolam by 3- to 4-fold and the Cmax by 2-fold, compared to placebo. Beta-blockers: Controlled and uncontrolled domestic studies suggest that concomitant use of diltiazem hydrochloride and beta-blockers is usually well tolerated Buspirone: In nine healthy subjects, diltiazem significantly increased the mean buspirone AUC 5.5-fold and Cmax 4. 1-fold compared to placebo. Carbamazepine: Concomitant administration of diltiazem with carbamazepine has been reported to result in elevated serum levels of carbamazepine (40% to 72% increase) resulting in toxicity in some cases. Cimetidine: A study in six healthy volunteers has shown a significant increase in peak diltiazem plasma levels (58%) and area-under-the-curve (53%) after a 1-week course of cimetidine at 1200 mg per day and a single dose of diltiazem 60 mg. Clonidine: Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with diltiazem. Cyclosporine: A pharmacokinetic interaction between diltiazem and cyclosporine has been observed during studies involving renal and cardiac transplant patients. Digitalis: Administration of diltiazem hydrochloride with digoxin in 24 healthy male subjects increased plasma digoxin concentrations approximately 20%. Ivabradine: Concurrent use of diltiazem increases exposure to ivabradine and may exacerbate bradycardia and conduction disturbances. Quinidine: Diltiazem significantly increases the AUC(0 → ∞) of quinidine by 51%, T1/2 by 36%, and decreases its CLoral by 33% Rifampin: Coadministration of rifampin with diltiazem lowered the diltiazem plasma concentrations to undetectable levels. Statins: Diltiazem is an inhibitor of CYP3A4 and has been shown to increase significantly the AUC of some statins.

The important consulting points on diltiazem are:

• CYP450 3A4 interactions: Patients taking other drugs that are substrates of CYP450 3A4 may require dosage adjustment when starting or stopping concomitantly administered diltiazem.
• Anesthetics: Calcium channel blockers may potentiate the effects of anesthetics.
• Benzodiazepines: Diltiazem may increase the effects of benzodiazepines.
• Beta-blockers: Concomitant use of diltiazem and beta-blockers is usually well tolerated, but may require monitoring.
• Buspirone: Diltiazem may increase the effects of buspirone.
• Carbamazepine: Concomitant administration of diltiazem and carbamazepine may result in elevated serum levels of carbamazepine.
• Cimetidine: Cimetidine may increase the plasma levels of diltiazem.
• Clonidine: Concomitant use of diltiazem and clonidine may result in sinus bradycardia.
• Cyclosporine: A pharmacokinetic interaction between diltiazem and cyclosporine has been observed.
• Digitalis: Diltiazem may increase the plasma concentrations of digoxin.
• Ivabradine: Concurrent use of diltiazem and ivabradine is not recommended.
• Quinidine: Diltiazem may increase the effects of quinidine.
• Rifampin: Coadministration of rifampin and diltiazem is not recommended.
• Statins: Diltiazem may increase the risk of myopathy and rhabdomyolysis with statins metabolized by CYP3A4 2.

From the Research

Important Consulting Points on Diltiazem

• Diltiazem is a calcium antagonist used to treat hypertension, angina, and supraventricular tachycardias 3
• The drug has demonstrated efficacy in patients with effort angina, and has been used intravenously to terminate supraventricular tachycardias and control the ventricular response to atrial fibrillation or flutter 3
• Common adverse events during diltiazem therapy include headache, flushing, peripheral oedema, and hypotension, with atrioventricular block being a rare but serious adverse event 3
• Diltiazem dosing strategies are important in the management of atrial fibrillation with rapid ventricular rate, with studies suggesting that a weight-based dose of ≥ 0.13 mg/kg may be more effective in achieving heart rate control 4
• Education and medication alerts can improve appropriate dosing of intravenous diltiazem in patients with atrial fibrillation or flutter with rapid ventricular response 5
• Intravenous diltiazem has been shown to be effective in controlling the ventricular response during atrial fibrillation or atrial flutter, with a response rate of 94% in one study 6
• Diltiazem has been compared to metoprolol in the management of atrial fibrillation or flutter with rapid ventricular rate, with one study finding that diltiazem was more effective in achieving rate control 7

Key Considerations for Diltiazem Use

• Diltiazem should be used with caution in patients with atrioventricular block, and coadministration with beta-adrenoceptor antagonists should be avoided, especially in the elderly 3
• Appropriate dosing of intravenous diltiazem is important to avoid hypotension and other adverse events 4, 5
• Diltiazem may be more effective than metoprolol in achieving rate control in patients with atrial fibrillation or flutter with rapid ventricular rate 7
• Education and medication alerts can improve appropriate use of diltiazem in clinical practice 5