What medications should be avoided in patients with bradycardia (abnormally slow heart rate)?

From the Guidelines

In patients with bradycardia, medications such as beta-blockers, non-dihydropyridine calcium channel blockers (e.g., diltiazem and verapamil), and ivabradine should be avoided or used with caution, as they can exacerbate bradycardia and worsen the condition. According to the 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia 1, ivabradine is contraindicated in patients with decompensated heart failure, severe hepatic impairment, or those with a blood pressure less than 90/50 mm Hg. Additionally, the guideline advises avoiding the use of ivabradine with concomitant strong CYP3A4 inhibitors or inducers, as well as with diltiazem, verapamil, and grapefruit juice.

Some key medications to avoid or use with caution in bradycardia include:

• Beta-blockers (e.g., metoprolol, propranolol, atenolol, and carvedilol)
• Non-dihydropyridine calcium channel blockers (e.g., diltiazem and verapamil)
• Ivabradine
• Cholinergic medications
• Certain antidepressants (particularly tricyclics)
• Clonidine
• Some opioids

It is essential to note that if a patient with bradycardia is already taking these medications, they should not abruptly discontinue them without medical supervision, as sudden withdrawal can cause rebound effects. Instead, they should consult their healthcare provider for appropriate medication adjustments. The reason these medications worsen bradycardia is that they either directly slow conduction through the heart's electrical system, decrease sympathetic stimulation of the heart, or enhance parasympathetic effects, all of which reduce heart rate, as mentioned in the guideline 1.

From the FDA Drug Label

Ivabradine: Concurrent use of verapamil increases exposure to ivabradine and may exacerbate bradycardia and conduction disturbances. Avoid co-administration of verapamil and ivabradine Beta-blockers: Concomitant therapy with beta-adrenergic blockers and verapamil may result in additive negative effects on heart rate, atrioventricular conduction and/or cardiac contractility. Digitalis: Clinical use of verapamil in digitalized patients has shown the combination to be well tolerated if digoxin doses are properly adjusted. However, chronic verapamil treatment can increase serum digoxin levels by 50% to 75% during the first week of therapy, and this can result in digitalis toxicity Ivabradine: Concurrent use of diltiazem increases exposure to ivabradine and may exacerbate bradycardia and conduction disturbances. Avoid concomitant use of ivabradine and diltiazem. Clonidine: Sinus bradycardia resulting in hospitalization and pacemaker insertion has been reported in association with the use of clonidine concurrently with diltiazem. Monitor heart rate in patients receiving concomitant diltiazem and clonidine Beta-blockers may exacerbate the rebound hypertension which can follow the withdrawal of clonidine. Both digitalis glycosides and beta-blockers slow atrioventricular conduction and decrease heart rate. Concomitant use can increase the risk of bradycardia

Medications to avoid in patients with bradycardia:

• Ivabradine: due to increased exposure and risk of exacerbating bradycardia and conduction disturbances when co-administered with verapamil or diltiazem 2, 3
• Beta-blockers: due to additive negative effects on heart rate, atrioventricular conduction, and/or cardiac contractility when co-administered with verapamil 2, and increased risk of bradycardia when co-administered with digitalis glycosides 4
• Clonidine: due to reported cases of sinus bradycardia resulting in hospitalization and pacemaker insertion when co-administered with diltiazem 3
• Digitalis glycosides: due to increased risk of digitalis toxicity when co-administered with verapamil 2, and increased risk of bradycardia when co-administered with beta-blockers 4

From the Research

Medications to Avoid in Patients with Bradycardia

• Beta-adrenergic receptor antagonist drugs (beta-blockers) and non-dihydropyridine calcium-channel blockers (non-DHP CCBs), such as diltiazem and verapamil, can cause sinus arrest or severe sinus bradycardia 5
• The combination of beta-blockers and non-DHP CCBs may have additive effects, increasing the risk of profound bradycardia 5
• Beta-blockers, such as atenolol and metoprolol, can lower heart rate, with the degree of reduction depending on the baseline heart rate 6, 7
• Non-DHP CCBs, such as verapamil and diltiazem, can also lower heart rate, although the effect may be less pronounced than with beta-blockers 6, 7
• Other medications, such as clonidine and hydrochlorothiazide, may also affect heart rate, although the impact on bradycardia is less clear 7

Specific Medications to Avoid

• Atenolol: can cause significant reductions in heart rate, particularly in patients with baseline heart rates < 65 beats/min 7
• Metoprolol: can lower heart rate, although the effect may be less pronounced than with atenolol 6, 8
• Diltiazem: can cause sinus arrest or severe sinus bradycardia, particularly when combined with beta-blockers 5
• Verapamil: can cause sinus arrest or severe sinus bradycardia, particularly when combined with beta-blockers 5