Interactions between Dronedarone and Edurant Ped
1 drug interaction and 10 additional warnings found for the following 2 drugs:
- dronedarone
- Edurant Ped (rilpivirine)
Drug interactions
Major drug interactions
Major:
dronedarone rilpivirine
Applies to: dronedarone and Edurant Ped (rilpivirine)
Contraindicated
Dronedarone may cause dose-related prolongation of the QT interval. Theoretically, coadministration with other agents that can prolong the QT interval may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. In healthy subjects given repeated oral doses, dronedarone induced a QTc prolongation of about 10 ms at 400 mg twice daily and up to 25 ms at 1600 mg twice daily. In clinical trials using a dosage of 400 mg twice daily, premature discontinuation of therapy due to QT prolongation occurred in 1.5% of dronedarone patients versus 0.5% of placebo patients. 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
Coadministration of dronedarone with other drugs that can prolong the QT interval is considered contraindicated.
References (4)
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
- Cerner Multum, Inc. "Australian Product Information."
- (2009) "Product Information. Multaq (dronedarone)." sanofi-aventis
Food/lifestyle interactions
Major food/lifestyle interactions
Major:
dronedarone Food/Lifestyle
Applies to: dronedarone
Generally avoid
Grapefruit juice may increase the plasma concentrations of dronedarone. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. According to the product labeling, administration with grapefruit juice resulted in a 2.5-fold increase in dronedarone peak plasma concentration and a 3-fold increase in systemic exposure. Because dronedarone is associated with concentration-dependent prolongation of the QT interval, increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes and sudden death.
Adjust dosing interval
Food increases the oral bioavailability of dronedarone. The mechanism of interaction is unknown. According to the product labeling, the absolute bioavailability of dronedarone increases from about 4% when administered in the fasted state to approximately 15% when administered with a high-fat meal.
Management
Patients treated with dronedarone should avoid consumption of grapefruit, grapefruit juice, and any supplement containing grapefruit extract. Dronedarone should be taken twice daily with the morning and evening meals.
References (1)
- (2009) "Product Information. Multaq (dronedarone)." sanofi-aventis
Moderate food/lifestyle interactions
Moderate:
rilpivirine Food/Lifestyle
Applies to: Edurant Ped (rilpivirine)
Generally avoid
Coadministration with grapefruit or grapefruit juice may increase the plasma concentrations of rilpivirine. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall induced by certain compounds present in grapefruit. In 15 study subjects given rilpivirine (150 mg once daily) with the potent CYP450 3A4 inhibitor ketoconazole (400 mg once daily), mean rilpivirine peak plasma concentration (Cmax), systemic exposure (AUC) and trough plasma concentration (Cmin) were increased by 30%, 49% and 76%, respectively. In 16 study subjects given a single 500 mg dose of a less potent CYP450 3A4 inhibitor chlorzoxazone two hours after rilpivirine (150 mg once daily), mean rilpivirine Cmax, AUC, and Cmin were increased by 17%, 25%, and 18%, respectively. Because grapefruit juice inhibits primarily intestinal rather than hepatic CYP450 3A4, the magnitude of interaction is greatest for those drugs that undergo significant presystemic metabolism by CYP450 3A4 (i.e., drugs with low oral bioavailability). 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. Pharmacokinetic interactions involving grapefruit juice are also subject to a high degree of interpatient variability, thus the extent to which a given patient may be affected is difficult to predict.
Adjust dosing interval
The administration of rilpivirine in a fasting state may decrease its oral absorption. Under fasted conditions, the systemic exposure to rilpivirine was 40% lower compared to normal or high-fat caloric meals (533 to 928 Kcal). The systemic exposure was 50% lower when rilpivirine was taken with a protein-rich nutritional beverage.
Management
Coadministration of grapefruit or grapefruit juice with rilpivirine should preferably be avoided. For optimal absorption, it is recommended to take rilpivirine on a regular schedule with a meal.
References (2)
- (2011) "Product Information. Edurant (rilpivirine)." Tibotec Pharmaceuticals
- Cerner Multum, Inc. (2015) "Canadian Product Information."
Disease interactions
8 potential interactions Applies to: 7 conditions, including Depression, Heart Failure, Psychosis, Liver Disease, and Long QT Syndrome.
Depression
Moderate:
Edurant Ped
The rilpivirine in Edurant Ped has a moderate potential interaction with Depression.
Depressive symptoms including suicide ideation and suicide attempts have been reported with the use of rilpivirine. Patients should be monitored for the appearance of these symptoms and should seek medical evaluation immediately if severe depressive symptoms occur. Caution should be used in patients with a history of depression or other psychiatric conditions.
Heart Block
Major:
dronedarone
Dronedarone has a major potential interaction with Heart Block.
Dronedarone has shown to double the risk of death in patients with symptomatic heart failure and recent decompensation requiring hospitalization or NYHA Class IV heart failure. It has also shown to double the risk of stroke and death and hospitalization due to heart failure in patients with atrial fibrillation. Other patients at risk include patients with second or third degree AV block, or sick sinus syndrome (except when used in conjunction with a functioning pacemaker), patients with bradycardia < 50 bpm, and patients with QT interval prolongation. The use of dronedarone is contraindicated in these patients.
Heart Failure
Major:
dronedarone
Dronedarone has a major potential interaction with Heart Failure.
Dronedarone has shown to double the risk of death in patients with symptomatic heart failure and recent decompensation requiring hospitalization or NYHA Class IV heart failure. It has also shown to double the risk of stroke and death and hospitalization due to heart failure in patients with atrial fibrillation. Other patients at risk include patients with second or third degree AV block, or sick sinus syndrome (except when used in conjunction with a functioning pacemaker), patients with bradycardia < 50 bpm, and patients with QT interval prolongation. The use of dronedarone is contraindicated in these patients.
Liver Disease
Major:
dronedarone
Dronedarone has a major potential interaction with Liver Disease.
Dronedarone is extensively metabolized by the liver. There is little clinical experience with moderate hepatic impairment and none in patients with severe hepatic impairment. No dosage adjustment is recommended for patients with moderate hepatic impairment, however its use is contraindicated in patients with severe hepatic impairment. Additionally hepatocellular liver injury, including acute liver failure has been reported in patients using dronedarone in the postmarketing setting. Patients should be advised to report immediately any symptoms suggesting hepatic injury, such as anorexia, nausea, vomiting, fever, malaise, fatigue, right upper quadrant pain, jaundice, dark urine or itching.
Moderate:
Edurant Ped
The rilpivirine in Edurant Ped has a moderate potential interaction with Liver Disease.
Hepatic adverse events have been reported in patients taking rilpivirine. Patients with underlying hepatitis B or C virus infection or marked transaminase elevations prior to therapy may be at increased risk for worsening or development of transaminase elevations; a few cases of hepatic toxicity have been reported in patients without preexisting hepatic disease or other known risk factors. Appropriate laboratory testing before starting therapy and monitoring for hepatotoxicity during therapy are recommended in patients with underlying hepatic disease (e.g., hepatitis B or C virus infection) or in patients with marked baseline transaminase elevations. Rilpivirine has not been studied in patients with severe liver dysfunction (Child-Pugh C); caution is recommended.
Long QT Syndrome
Major:
dronedarone
Dronedarone has a major potential interaction with Long QT Syndrome.
Dronedarone has shown to double the risk of death in patients with symptomatic heart failure and recent decompensation requiring hospitalization or NYHA Class IV heart failure. It has also shown to double the risk of stroke and death and hospitalization due to heart failure in patients with atrial fibrillation. Other patients at risk include patients with second or third degree AV block, or sick sinus syndrome (except when used in conjunction with a functioning pacemaker), patients with bradycardia < 50 bpm, and patients with QT interval prolongation. The use of dronedarone is contraindicated in these patients.
Psychosis
Moderate:
Edurant Ped
The rilpivirine in Edurant Ped has a moderate potential interaction with Psychosis.
Depressive symptoms including suicide ideation and suicide attempts have been reported with the use of rilpivirine. Patients should be monitored for the appearance of these symptoms and should seek medical evaluation immediately if severe depressive symptoms occur. Caution should be used in patients with a history of depression or other psychiatric conditions.
Renal Dysfunction
Moderate:
Edurant Ped
The rilpivirine in Edurant Ped has a moderate potential interaction with Renal Dysfunction.
Rilpivirine should be used with caution and with increased monitoring for side effects in patients with severe renal dysfunction or end-stage renal disease, as drug concentrations can be increased due to alteration of drug absorption, distribution, and metabolism secondary to renal dysfunction. No dose adjustment is required in patients with mild or moderate renal dysfunction.
Report options
More resources
dronedarone
A total of 755 drugs are known to interact with dronedarone.
- Dronedarone is in the drug class group III antiarrhythmics.
- Dronedarone is used to treat the following conditions:
Edurant Ped
A total of 440 drugs are known to interact with Edurant Ped.
- Edurant ped is in the drug class NNRTIs.
- Edurant ped is used to treat HIV-1 Infection.
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
Always consult your healthcare provider to ensure the information displayed on this page applies to your personal circumstances.