Can timolol (beta blocker) eye drops cause bradycardia (abnormally slow heart rate)?

Timolol Eye Drops and Bradycardia Risk

Yes, timolol eye drops absolutely can cause bradycardia and other serious cardiac effects, including potentially life-threatening complete heart block, despite being administered topically. 1, 2

Mechanism of Systemic Absorption

• Approximately 80% of topically administered timolol is systemically absorbed through ocular tissues, bypassing first-pass hepatic metabolism and producing beta-adrenergic blockade throughout the body equivalent to oral beta-blockers 3, 4
• This systemic absorption causes the same cardiovascular effects as oral beta-blockers, including bradycardia, heart block, and cardiac arrest 1, 2

Documented Cardiac Effects

The severity of timolol-induced bradycardia ranges from asymptomatic heart rate reduction to life-threatening complications:

• Complete (third-degree) atrioventricular block requiring hospitalization has been documented 5
• Heart rates dropping to 29-33 beats per minute with symptomatic bradycardia and syncope requiring emergency care 5, 6
• Some patients with glaucoma have required permanent pacemaker implantation due to timolol-associated bradycardia 1
• Second and third degree heart block and cardiac arrest have occurred with overdosage 2

FDA Contraindications

Timolol eye drops are explicitly contraindicated in patients with:

• Sinus bradycardia 2
• Second or third degree atrioventricular block 2
• Overt cardiac failure or cardiogenic shock 2

High-Risk Patient Populations

Certain patients face substantially elevated risk of bradycardia:

• CYP2D6 poor metabolizers have highest plasma timolol concentrations and are most prone to bradycardia, as timolol is primarily metabolized by the polymorphic CYP2D6 enzyme 3, 4, 7
• Patients taking CYP2D6 inhibitors (paroxetine, fluoxetine, sertraline) experience impaired timolol metabolism and prolonged bradycardic effects 4, 7
• Concomitant use of other beta-blockers or verapamil creates additive bradycardic effects 1, 4
• Elderly patients are more susceptible to cardiovascular adverse effects 1

Clinical Correlation

• Plasma timolol levels directly correlate with heart rate reduction, particularly during exercise when beta-adrenergic tone is elevated 3
• The 0.5% aqueous formulation produces larger cardiovascular effects than 0.1% hydrogel formulations 3

Critical Clinical Pitfall

Bradycardia may not resolve immediately after timolol discontinuation:

• One documented case showed gradual resolution over 23 days, with bradycardia constituting 19.9%, 13.9%, 0.2%, and 0% of recorded time at days 2,9,16, and 23 respectively 7
• Some patients experience unexpected bradycardia relapse weeks to months after discontinuation, suggesting unmasking of underlying sinus node dysfunction 5, 7
• Patients who develop timolol-induced bradycardia require long-term cardiac follow-up even after symptom resolution 5

Recommended Screening

Prior to initiating timolol eye drops:

• Obtain baseline ECG in all patients 4
• Consider CYP2D6 genotyping if routinely available 4
• Screen for concomitant medications that inhibit CYP2D6 or provide additional beta-blockade 4