Interactions between Fidaxomicin and Propafenone
1 drug interaction and 13 additional warnings found for the following 2 drugs:
- fidaxomicin
- propafenone
Drug interactions
Minor drug interactions
Minor:
propafenone fidaxomicin
Applies to: propafenone and fidaxomicin
Coadministration with inhibitors of P-glycoprotein (P-gp) may increase the plasma concentrations of fidaxomicin and its main metabolite, OP-1118, both of which are substrates of the intestinal efflux transporter. When fidaxomicin 200 mg was administered in combination with cyclosporine 200 mg in 14 study subjects, fidaxomicin peak plasma concentration (Cmax) and systemic exposure (AUC) increased by an average of 4.2- and 1.9-fold, respectively, compared to when administered alone. The Cmax and AUC of OP-1118 was increased by 9.5- and 4.1-fold, respectively, with cyclosporine. Theoretically, concentrations of fidaxomicin and OP-1118 may also be decreased at the site of action (i.e., gastrointestinal tract) due to P-gp inhibition. However, concomitant use of a P-gp inhibitor had no attributable effect on safety or efficacy of fidaxomicin in controlled clinical trials. No dosage adjustment is recommended when fidaxomicin is coadministered with P-gp inhibitors.
References (1)
- (2011) "Product Information. Dificid (fidaxomicin)." Optimer Pharmaceuticals
Food/lifestyle interactions
Moderate food/lifestyle interactions
Moderate:
propafenone Food/Lifestyle
Applies to: 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 (4)
- 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
- (2011) "Product Information. Rythmol SR (propafenone)." GlaxoSmithKline
- (2023) "Product Information. Apo-Propafenone (propafenone)." Apotex Incorporated
- (2022) "Product Information. Propafenone (propafenone)." Accord-UK Ltd
Disease interactions
12 potential interactions Applies to: 11 conditions, including Heart Failure, Asthma, COPD, Hypokalemia, and Hypotension.
Asthma
Major:
propafenone
Propafenone has a major potential interaction with Asthma.
The use of propafenone is contraindicated in patients with bronchospastic disorders or severe obstructive pulmonary disease. Propafenone has beta-adrenergic blocking properties.
COPD
Major:
propafenone
Propafenone has a major potential interaction with COPD.
The use of propafenone is contraindicated in patients with bronchospastic disorders or severe obstructive pulmonary disease. Propafenone has beta-adrenergic blocking properties.
Heart Block
Major:
propafenone
Propafenone has a major potential interaction with Heart Block.
The use of propafenone is contraindicated in patients with uncontrolled congestive heart failure, cardiogenic shock, bradycardia, or marked hypotension. Propafenone can exacerbate congestive heart failure by beta blockade of sympathetic stimulation necessary for circulatory support. Propafenone also has negative inotropic activity that can depress cardiac output and cardiac index.
Major:
propafenone
Propafenone has a major potential interaction with Heart Block.
The use of propafenone is contraindicated in patients with conduction disorders such as second- or third-degree AV block, right bundle-branch block when associated with a left hemiblock(bifascicular block), sick sinus syndrome, or bradycardia-tachycardia syndrome in the absence of a functional artificial pacemaker.
Heart Failure
Major:
propafenone
Propafenone has a major potential interaction with Heart Failure.
The use of propafenone is contraindicated in patients with uncontrolled congestive heart failure, cardiogenic shock, bradycardia, or marked hypotension. Propafenone can exacerbate congestive heart failure by beta blockade of sympathetic stimulation necessary for circulatory support. Propafenone also has negative inotropic activity that can depress cardiac output and cardiac index.
Hyperkalemia
Moderate:
propafenone
Propafenone has a moderate potential interaction with Hyperkalemia.
Electrolyte imbalance can alter the therapeutic effectiveness of antiarrhythmic agents. Hypokalemia and hypomagnesemia can reduce the effectiveness of antiarrhythmic agents. In some cases, these disorders can exaggerate the degree of QTc prolongation and increase the potential for torsade de pointes. Hyperkalemia can potentiate the toxic effects of antiarrhythmic agents. Electrolyte imbalance should be corrected prior to initiating antiarrhythmic therapy. Clinical monitoring of cardiac function and electrolyte concentrations is recommended.
Hypokalemia
Moderate:
propafenone
Propafenone has a moderate potential interaction with Hypokalemia.
Electrolyte imbalance can alter the therapeutic effectiveness of antiarrhythmic agents. Hypokalemia and hypomagnesemia can reduce the effectiveness of antiarrhythmic agents. In some cases, these disorders can exaggerate the degree of QTc prolongation and increase the potential for torsade de pointes. Hyperkalemia can potentiate the toxic effects of antiarrhythmic agents. Electrolyte imbalance should be corrected prior to initiating antiarrhythmic therapy. Clinical monitoring of cardiac function and electrolyte concentrations is recommended.
Hypotension
Major:
propafenone
Propafenone has a major potential interaction with Hypotension.
The use of propafenone is contraindicated in patients with uncontrolled congestive heart failure, cardiogenic shock, bradycardia, or marked hypotension. Propafenone can exacerbate congestive heart failure by beta blockade of sympathetic stimulation necessary for circulatory support. Propafenone also has negative inotropic activity that can depress cardiac output and cardiac index.
Liver Disease
Moderate:
propafenone
Propafenone has a moderate potential interaction with Liver Disease.
Propafenone is extensively metabolized by the liver. The bioavailability of propafenone in patients with normal hepatic function is approximately 3% to 40%, but increases to approximately 70% in patients with severe hepatic impairment. Therapy with propafenone should be administered cautiously and the dosage reduced to 20% to 30% of that given patients with normal hepatic function. Clinical monitoring of cardiac function (ECG) and hepatic function is recommended.
Lupus Erythematosus
Moderate:
propafenone
Propafenone has a moderate potential interaction with Lupus Erythematosus.
Reversible (+) ANA titers have been reported during administration of propafenone. Therapy with propafenone should be administered cautiously in patients with established systemic lupus erythematosus (SLE). Clinical monitoring, including ANA titers, is recommended. Patients without a previous history of (+) ANA titer or SLE who develop a (+) ANA while receiving propafenone should be evaluated and, if ANA titers persist or worsen, discontinuation of therapy should be considered.
Magnesium Imbalance
Moderate:
propafenone
Propafenone has a moderate potential interaction with Magnesium Imbalance.
Electrolyte imbalance can alter the therapeutic effectiveness of antiarrhythmic agents. Hypokalemia and hypomagnesemia can reduce the effectiveness of antiarrhythmic agents. In some cases, these disorders can exaggerate the degree of QTc prolongation and increase the potential for torsade de pointes. Hyperkalemia can potentiate the toxic effects of antiarrhythmic agents. Electrolyte imbalance should be corrected prior to initiating antiarrhythmic therapy. Clinical monitoring of cardiac function and electrolyte concentrations is recommended.
Renal Dysfunction
Moderate:
propafenone
Propafenone has a moderate potential interaction with Renal Dysfunction.
Propafenone is partially eliminated by the kidney and approximately 50% of its metabolites are excreted in the urine. Therapy with propafenone should be administered cautiously in patients with renal impairment, monitoring for signs of overdosage.
Report options
More resources
fidaxomicin
A total of 169 drugs are known to interact with fidaxomicin.
- Fidaxomicin is in the drug class macrolides.
- Fidaxomicin is used to treat Clostridioides difficile Infection.
propafenone
A total of 461 drugs are known to interact with propafenone.
- Propafenone is in the drug class group I antiarrhythmics.
- Propafenone is used to treat the following conditions:
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| 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. | |
| No interaction information available. |
Further information
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