What are the interactions of propafenone with other medications, particularly contraindicated interactions?

From the Guidelines

Propafenone should not be taken with other medications that prolong the QT interval, such as certain antipsychotics and antibiotics, due to the increased risk of torsades de pointes 1. When considering the interactions of propafenone with other medications, it's crucial to prioritize those that are contraindicated due to their potential to significantly increase morbidity, mortality, and negatively impact quality of life. Some key points to consider include:

• Concomitant use of propafenone with strong CYP2D6 inhibitors, such as fluoxetine and paroxetine, is contraindicated as it can lead to increased propafenone blood levels and toxicity 1.
• The use of beta-blockers, like metoprolol, with propafenone may enhance negative inotropic effects, leading to excessive bradycardia or heart failure, and should be avoided or closely monitored 1.
• Propafenone can increase the levels of warfarin, digoxin, theophylline, and cyclosporine, necessitating dose adjustments and more frequent monitoring of these medications to prevent adverse effects 1.
• Interactions with local anesthetics can potentially cause CNS toxicity, highlighting the need for caution when propafenone is used in conjunction with these agents 1. Given the potential for these interactions to significantly impact patient outcomes, it is essential to carefully evaluate a patient's medication regimen before initiating propafenone therapy and to closely monitor for signs of adverse interactions 1.

From the FDA Drug Label

Drug Interactions Quinidine Small doses of quinidine completely inhibit the hydroxylation metabolic pathway, making all patients, in effect, slow metabolizers (see CLINICAL PHARMACOLOGY). There is, as yet, too little information to recommend concomitant use of propafenone and quinidine. Local Anesthetics Concomitant use of local anesthetics (i. e., during pacemaker implantations, surgery, or dental use) may increase the risks of central nervous system side effects. Digitalis Propafenone hydrochloride produces dose-related increases in serum digoxin levels ranging from about 35% at 450 mg/day to 85% at 900 mg/day of propafenone without affecting digoxin renal clearance Beta-Antagonists In a study involving healthy subjects, concomitant administration of propafenone and propranolol has resulted in substantial increases in propranolol plasma concentration and elimination half-life with no change in propafenone plasma levels from control values. Warfarin In a study of eight healthy subjects receiving propafenone and warfarin concomitantly, mean steady-state warfarin plasma concentrations increased 39% with a corresponding increase in prothrombin times of approximately 25% Cimetidine Concomitant administration of propafenone and cimetidine in 12 healthy subjects resulted in a 20% increase in steady-state plasma concentrations of propafenone Desipramine Concomitant administration of propafenone and desipramine may result in elevated serum desipramine levels. Cyclosporin Propafenone therapy may increase levels of cyclosporin Theophylline Propafenone may increase theophylline concentration during concomitant therapy with the development of theophylline toxicity. Rifampin Rifampin may accelerate the metabolism and decrease the plasma levels and antiarrhythmic efficacy of propafenone

The interactions of propafenone with other medications include:

• Contraindicated interactions: The use of propafenone with quinidine is not recommended due to the lack of information on their concomitant use 2.
• Caution advised:
  • Local anesthetics may increase the risk of central nervous system side effects.
  • Digitalis levels may increase, requiring dose adjustment.
  • Beta-antagonists (e.g., propranolol, metoprolol) may have increased plasma concentrations.
  • Warfarin levels may increase, requiring monitoring of prothrombin times.
  • Cimetidine may increase propafenone plasma concentrations.
  • Desipramine levels may be elevated.
  • Cyclosporin levels may be increased.
  • Theophylline toxicity may occur due to increased concentrations.
  • Rifampin may decrease propafenone plasma levels and efficacy. It is essential to carefully monitor patients and adjust doses as necessary when propafenone is used concomitantly with these medications 2 2.

From the Research

Interactions of Propafenone with Other Medications

The interactions of propafenone with other medications are crucial to understand, especially the contraindicated interactions, to ensure safe and effective use.

• Contraindicated Interactions: There are no direct mentions of specific contraindicated interactions with other medications in the provided studies 3, 4, 5, 6, 7. However, it's known that propafenone, like other antiarrhythmic drugs, may interact with various medications, potentially leading to adverse effects.
• Potential Interactions:
  • Propafenone may interact with other antiarrhythmic agents, increasing the risk of proarrhythmic effects or other cardiac toxicities 5, 6.
  • The use of propafenone with beta-blockers or calcium channel blockers may require careful monitoring due to potential additive effects on heart rate or conduction 3, 6.
  • Patients on medications that affect the cytochrome P450 system, particularly those that inhibit or induce CYP2D6 and CYP1A2, may experience altered propafenone levels, as propafenone is metabolized by these enzymes 6.
• Precautions and Monitoring: Given the potential for interactions and the complexity of propafenone's pharmacokinetics, careful patient monitoring is advised, especially when initiating or adjusting propafenone therapy in conjunction with other medications 4, 6. Regular ECG monitoring and assessment of liver function may be necessary to minimize risks 3, 7.

It's essential to consult comprehensive drug interaction resources and clinical guidelines for the most current and detailed information on managing propafenone interactions with other medications.