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Drug Interactions between procainamide and Rythmol

This report displays the potential drug interactions for the following 2 drugs:

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Interactions between your drugs

Major

procainamide propafenone

Applies to: procainamide and Rythmol (propafenone)

GENERALLY AVOID: Coadministration of propafenone with Class IA antiarrhythmic agents may produce additive effects on the QT interval of the electrocardiogram. Theoretically, this may increase the risk of ventricular arrhythmias including torsade de pointes and sudden death. Conflicting information exists as to whether propafenone alone prolongs the QT interval. Some clinicians suggest it does, although data in the medical literature do not support a clinically significant effect of propafenone and other Class IC agents on the QT interval. Moreover, because propafenone prolongs the QRS interval in the electrocardiogram, any changes in the QT interval are difficult to interpret. Nevertheless, proarrhythmic effects including sudden death and life-threatening ventricular arrhythmias such as ventricular fibrillation, ventricular tachycardia, asystole, and torsade de pointes have been associated with its use. Since propafenone has not been extensively studied for use in conjunction with other antiarrhythmic agents or agents that prolong the QT interval, caution may be advisable. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).

MANAGEMENT: Propafenone product labeling recommends that concomitant use with Class IA and III antiarrhythmic agents be avoided. In addition, these agents should be withheld for at least 5 half-lives prior to dosing with propafenone. Close monitoring of clinical response, ECG, and drug levels is recommended if concomitant use is required. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.

References

  1. Hii JT, Wyse DG, Gillis AM, et al. (1991) "Propafenone-induced torsade de pointes: cross-reactivity with quinidine." Pacing Clin Electrophysiol, 14, p. 1568-70
  2. Zehender M, Hohnloser S, Geibel A, et al. (1992) "Short-term and long-term treatment with propafenone: determinants of arrhythmia suppression, persistence of efficacy, arrhythmogenesis, and side effects in patients." Br Heart J, 67, p. 491-7
  3. Klein RC, Huang SK, Marcus FI, et al. (1987) "Enhanced antiarrhythmic efficacy of propafenone when used in combination with procainamide or quinidine." Am Heart J, 114, p. 551-8
  4. Buss J, Neuss H, Bilgin Y, Schlepper M (1985) "Malignant ventricular tachyarrhythmias in association with propafenone treatment." Eur Heart J, 6, p. 424-8
  5. "Product Information. Rythmol (propafenone)." Knoll Pharmaceutical Company
  6. (2011) "Product Information. Rythmol SR (propafenone)." GlaxoSmithKline
View all 6 references

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Drug and food interactions

Moderate

propafenone food

Applies to: Rythmol (propafenone)

GENERALLY AVOID: Grapefruit juice may increase the plasma concentrations of propafenone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. Inhibition of hepatic CYP450 3A4 may also contribute. In over 90% of patients, propafenone is rapidly and extensively converted to 2 active metabolites: 5-hydroxypropafenone via CYP450 2D6 and N-depropylpropafenone (norpropafenone) via CYP450 3A4 and 1A2. In less than 10% of patients (approximately 6% of Caucasians in the U.S. population), however, metabolism of propafenone is slower because the 5-hydroxy metabolite is not formed, or minimally formed, due to a genetic deficiency in CYP450 2D6. In these poor metabolizers of CYP450 2D6, clearance of propafenone via the CYP450 3A4 and 1A2 metabolic pathways becomes more important, and inhibition of these pathways may substantially increase systemic exposure to propafenone. Likewise, patients taking concomitant inhibitors of CYP450 2D6 and 3A4 may experience similar pharmacokinetic effects. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Increased systemic exposure to propafenone may result in proarrhythmic events and exaggerated beta-adrenergic blocking activity.

MANAGEMENT: It may be advisable for patients to avoid the consumption of grapefruit, grapefruit juice, or supplements that contain grapefruit during treatment with propafenone.

References

  1. Botsch S, Gautier JC, Beaune P, Eichelbaum M, Kroemer HK (1993) "Identification and characterization of the cytochrome P450 enzymes involved in N-dealkylation of propafenone: molecular base for interaction potential and variable disposition of active metabolites." Mol Pharmacol, 43, p. 120-6
  2. (2011) "Product Information. Rythmol SR (propafenone)." GlaxoSmithKline
  3. (2023) "Product Information. Apo-Propafenone (propafenone)." Apotex Incorporated
  4. (2022) "Product Information. Propafenone (propafenone)." Accord-UK Ltd
View all 4 references

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Minor

procainamide food

Applies to: procainamide

Ethanol may increase the acetylation of procainamide. Subtherapeutic plasma levels of procainamide may result in some patients. Because the acetylated metabolite of procainamide also possesses antiarrhythmic properties, the clinical effects are unclear.

References

  1. Olsen H, Morland J (1982) "Ethanol-induced increase in procainamide acetylation in man." Br J Clin Pharmacol, 13, p. 203-8

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Therapeutic duplication warnings

Therapeutic duplication is the use of more than one medicine from the same drug category or therapeutic class to treat the same condition. This can be intentional in cases where drugs with similar actions are used together for demonstrated therapeutic benefit. It can also be unintentional in cases where a patient has been treated by more than one doctor, or had prescriptions filled at more than one pharmacy, and can have potentially adverse consequences.

Duplication

Antiarrhythmics

Therapeutic duplication

The recommended maximum number of medicines in the 'antiarrhythmics' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'antiarrhythmics' category:

  • procainamide
  • Rythmol (propafenone)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

Duplication

Group i antiarrhythmics

Therapeutic duplication

The recommended maximum number of medicines in the 'group I antiarrhythmics' category to be taken concurrently is usually one. Your list includes two medicines belonging to the 'group I antiarrhythmics' category:

  • procainamide
  • Rythmol (propafenone)

Note: In certain circumstances, the benefits of taking this combination of drugs may outweigh any risks. Always consult your healthcare provider before making changes to your medications or dosage.

See also

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Drug Interaction Classification

These classifications are only a guideline. The relevance of a particular drug interaction to a specific individual is difficult to determine. Always consult your healthcare provider before starting or stopping any medication.
Major Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit.
Moderate Moderately clinically significant. Usually avoid combinations; use it only under special circumstances.
Minor Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan.
Unknown No interaction information available.

Further information

Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.

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