Does loperamide affect heart rate?

Loperamide and Heart Rate Effects

At therapeutic doses, loperamide does not significantly affect heart rate, but at supratherapeutic doses or with abuse, it can cause serious cardiac arrhythmias including bradycardia, tachycardia, QT prolongation, and ventricular arrhythmias that may be life-threatening. 1

Therapeutic Use and Cardiac Safety

When used at recommended therapeutic doses for diarrhea management:

• Loperamide is generally well-tolerated with no significant effects on heart rate
• The maximum recommended daily dose is 16 mg 2
• Loperamide acts primarily on μ-opioid receptors in the gastrointestinal tract with minimal systemic absorption 3

Cardiac Effects at Supratherapeutic Doses

At doses exceeding therapeutic recommendations, loperamide can cause:

• QT/QTc interval prolongation
• QRS interval prolongation (starting at concentrations ~1200 times the therapeutic plasma concentration) 4
• Bradycardia
• Ventricular tachycardia, including Torsades de Pointes
• Brugada syndrome pattern on ECG 5
• Syncope
• Cardiac arrest
• Death 1

Mechanism of Cardiotoxicity

Loperamide's cardiac effects at high doses are due to:

• Inhibition of hERG (IKr) potassium channels (IC50 of 0.390 μM)
• Blockade of sodium channels (IC50 of 0.526 μM)
• Inhibition of calcium channels (IC50 of 4.091 μM) 4

These effects occur at concentrations far exceeding therapeutic levels (>1560 times the free therapeutic plasma concentration).

Risk Factors for Cardiac Toxicity

Increased risk of cardiac effects may occur with:

• Intentional misuse or abuse (doses reported from 70-1600 mg daily) 1
• Long-term high-dose use 3
• Concomitant use of medications that inhibit P-glycoprotein (allowing greater CNS penetration)
• Pre-existing QT prolongation
• Electrolyte abnormalities
• Co-administration with other QT-prolonging medications 2

Case Reports of Cardiac Toxicity

Several documented cases highlight the cardiac risks:

• A 25-year-old who abused loperamide experienced syncope, bradycardia, ventricular tachycardia, QTc of 527 ms, QRS of 170 ms, and subsequent cardiac arrest and death 1
• A 54-year-old using 144 mg daily for chronic diarrhea for over 2 years developed syncope, QT prolongation of 500 ms, sinus arrest, and polymorphic ventricular tachycardia 1, 3
• A 48-year-old taking 40-80 tablets (80-160 mg) daily presented with QRS 164 ms, QT 582 ms, and multiple runs of non-sustained ventricular tachycardia 6

Clinical Implications

For healthcare providers:

• Consider loperamide toxicity in patients with unexplained arrhythmias, especially with history of opioid abuse 7
• Monitor ECG in patients suspected of loperamide overuse
• Be aware that cardiac effects may persist for days (median time to ECG normalization: 5 days) 7
• Recognize that standard antiarrhythmic medications may be ineffective in loperamide-induced arrhythmias 1

Management of Loperamide Cardiotoxicity

For suspected cardiac toxicity:

• Promptly discontinue loperamide
• Provide supportive care and cardiac monitoring
• Consider naloxone for CNS and respiratory depression
• Manage arrhythmias (electrical cardioversion, overdrive pacing, or isoproterenol may be required)
• Correct electrolyte abnormalities
• Monitor until ECG normalizes 1, 7

Appropriate Use Guidelines

To minimize cardiac risks:

• Adhere to recommended dosing (maximum 16 mg/day) 2
• Use loperamide for short-term management of diarrhea (generally limited to 3 days) 2
• Discontinue if symptoms worsen or if dysentery develops 2
• Consider alternative anti-diarrheals in patients with cardiac risk factors