Overview:
Dronedarone is a drug called heart rhythm medicine for a rhythm disorder known as atrial fibrillation. This medicine is given to adults who suffered from rhythm disorder in the past but now have normal heart rhythms. However, the drug has to be prescribed cautiously as it may increase the chances of death if mishandled. Dronedarone helps maintain a normal heart rhythm and lowers the chances of going to the hospital for atrial fibrillation.
How Does Dronedarone Work?
Dronedarone is used in patients with a previous history of irregular heartbeats (either persistent atrial fibrillation or paroxysmal) but presently have a normal heartbeat. The drug functions to keep the heartbeat low so that there is no need to go to the hospital due to atrial fibrillation. However, the drug should not be used in cases of permanent atrial fibrillation because it may lead to serious side effects.
Precautions for Taking Dronedarone:
Allergies: It is essential to tell the doctor about any allergic reactions before starting the drug because Dronedarone may contain some inactive ingredients, which may lead to allergies or other problems.
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Taking a patient's history for any liver disease or irregular heartbeat is essential as the medicine might have serious side effects in such cases.
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Dronedarone may affect the heart rhythm by extending the QT prolongation. This may cause fast and irregular heartbeats, which can be fatal. This may lead to symptoms such as dizziness and fainting.
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Low levels of magnesium and potassium also increase the chance of QT prolongation. This happens due to the consumption of water pills or diuretics. It is important to mention the administration of these drugs to the doctor before starting Dronedarone.
Warning:
Dronedarone is not recommended in cases of permanent atrial fibrillation as it may increase the risk of death and cause some severe heart conditions. It is important to consult the doctor if there is an irregular pulse, wheezing, or chest tightness.
For Patients:
What Is Atrial Fibrillation?
Atrial fibrillation is an irregular and generally rapid heart rhythm that can lead to blood clot formation in the heart. It can potentially develop risks of heart stroke, heart failure, and other heart complications. In atrial fibrillation cases, the heart's upper chambers, known as atria, beats irregularly and chaotically. The atria do not sync with the lower chambers, known as ventricles. The episodes of atrial fibrillation may be persistent or it may come and go.
What Are the Symptoms of Atrial Fibrillation?
Generally, people suffering from atrial fibrillation do not notice any symptoms, but if they appear, they are:
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Chest pain.
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Fatigue and dizziness.
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Reduced ability to exercise.
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Shortness of breath.
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Weakness and lightheadedness.
What Are the Types of Atrial Fibrillation?
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Persistent: This type of atrial fibrillation is continuous and does not go back to its normal position on its own.
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Occasional (Paroxysmal Atrial Fibrillation): The symptoms of atrial fibrillation come and go within a few minutes to hours. Sometimes the episodes may last for around a week and it can be repeated.
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Long-Standing Persistent: This type of fibrillation is continuous and may last up to twelve months.
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Permanent: Atrial fibrillation is permanent, in which the heartbeat cannot be restored. Medications are required to control the heartbeat and prevent clot formation.
Before Taking the Drug:
Things to Tell the Doctor Before Taking the Drug:
Some conditions should be considered before starting the drug Dronedarone.
These are:
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Severe heart conditions such as AV block, sick sinus syndrome, or in cases of slow heartbeats may lead to fainting.
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Severe liver diseases may interfere with the metabolism of the drug.
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If there were lung or liver problems after consumption of a drug called Amiodarone.
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In case of pregnancy or breastfeeding, it may affect infants' development.
Contraindications for Dronedarone:
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Cases of severe heart failure.
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If the person is recently hospitalized for severe heart failure symptoms such as chest tightness, shortness of breath, swelling, or rapid weight gain.
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Cases of atrial fibrillation are permanent. It cannot be changed back to a normal rhythm.
While Taking the Drug:
Doses of Dronedarone:
The drug is consumed in a quantity of 400 mg in the oral form twice a day with a meal in the morning and evening.
How to Take Dronedarone?
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All the directions mentioned on the prescription and the label of the medicine should be followed correctly.
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The drug is generally consumed in the morning and evening meals.
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Regular follow-up is required every three months to check the heart's rhythm. This helps to figure out whether Dronedarone is needed anymore or not. The drug should not be stopped without the doctor's advice.
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The pulse should be regulated often to check for any irregular rhythm.
What Happens if a Dose Is Missed?
If one dose is missed, the next dose should be taken at the usual time instead of two doses simultaneously. Taking two doses at a time may lead to severe complications in the heart.
Food to Avoid While Taking Dronedarone:
Grapefruit may interact with Dronedarone and lead to some side effects. It is thus recommended to avoid the consumption of Dronedarone with grapefruit.
After Taking the Drug:
Side Effects of Dronedarone:
Dronedarone may lead to some severe side effects such as:
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Shortness of breath and dry cough.
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Less or no urination.
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Heart issues lead to rapid weight gain, swelling, and shortness of breath.
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Liver problems lead to stomach pain in the upper right of the abdomen, loss of appetite, tiredness, dark urine, and jaundice (yellowing of the eyes and skin).
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Fast or pounding heartbeats, shortness of breath, fluttering in the chest, and sudden dizziness.
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Dronedarone may lead to lower levels of magnesium or potassium, which causes dizziness, numbness or tingling in the limbs, fluttering in the chest, increased urination, or thirst.
Some of the Common Side Effects of Dronedarone are:
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Feeling of weakness and tiredness.
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Stomach pain, nausea, indigestion, diarrhea, and vomiting.
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Redness, itching, and skin rashes.
Overdose of Dronedarone:
The overconsumption of Dronedarone leads to either severe breathing issues or passing out. Thus it is advised to take the drug with lots of precautions.
For the Doctor:
Indications:
Dronedarone is a class three antiarrhythmic drug indicated in cases of irregular rhythm in patients with paroxysmal or persistent atrial fibrillation. Atrial fibrillation is a common prolonged arrhythmia where the treatment is focused on the prevention of stroke and related symptoms. The irregular rhythm is managed by controlling the rhythm, preventing thromboembolic events, and treating the underlying disease. Dronedarone works similarly to Amiodarone as a multiple channel blocker and controls rhythm and atrial fibrillation.
Pharmacodynamics:
Dronedarone helps to restore normal sinus rhythm by preventing ventricular tachycardia and ventricular fibrillation. Dronedarone prolongs the QTc interval by about an average of 10 ms. The drug decreases blood pressure (atrial) and then reduces oxygen consumption. Dronedarone decreases myocardial contractility with no changes in the left ventricular ejection fraction. Dronedarone helps to vasodilate coronary arteries by activating the nitric oxide pathway. It helps reduce the chances of hospitalization due to acute coronary syndrome and decreases the chances of stroke.
Dronedarone has antiadrenergic effects and reduces the alpha-adrenergic blood pressure in response to beta 1, beta 2, and epinephrine. It also inhibits triiodothyronine signals by binding to TR alpha 1 and a little binding to the TR beta 1 receptors. Dronedarone doses must be managed precisely as it may be fatal if overdosed. When compared to Amiodarone, Dronedarone has both faster onset and offset of action with a low tissue accumulation and shorter elimination half-life.
Mechanism of Action:
Atrial fibrillation is a common type of arrhythmia caused by abnormal electrical activity in the atria. In atrial fibrillation, the irregular heart rate is tachyarrhythmia (faster heart rate) which can be either paroxysmal (less than seven days) or persistent (lasts longer). Atrial fibrillation may cause turbulent and abnormal blood flow through the heart's chambers. This may lead to decreased effectiveness of the heart to pump the blood and increase the chances of thrombus formation in the atria. This ultimately causes a stroke.
Dronedarone controls the rhythm and helps to achieve heart rate in atrial fibrillation. It decreases the extreme rate of the rise of an action potential in a frequency-dependent and concentrated manner. It is a multi-channel blocker that meets all the criteria of the four Vaughan Williams antiarrhythmic drug classes. Still, the effect of each of these on the drug's antiarrhythmic effect is unknown.
Dronedarone inhibits the rapid sodium currents, non-competitively antagonizes alpha and beta-adrenergic receptors and blocks slow calcium inward currents. More specifically, the drug slows down delayed rectifier potassium current, inward rectifier potassium current, and L - type calcium ion current. Dronedarone decelerates cardiac conduction, increases refractory periods, and extends the action potential and refractory periods.
Absorption:
Dronedarone is sufficiently absorbed when administered through oral routes. More than 70 % of absorption takes place in such cases. It is known to display low systemic bioavailability due to extensive first-pass metabolism. When consumed with a high-fat meal, its bioavailability is 15 %, whereas, without a meal, the bioavailability reduces by 4 %. The plasma concentration of Dronedarone and its primary circulating N-debutyl metabolite reaches its peak within three to six hours after administering the drug with a meal. Repeated administration of 400 mg Dronedarone twice daily leads to a stable state within four to eight days of initial treatment.
Volume of Distribution:
At the steady state, the volume of distribution ranges from twelve hundred to fourteen hundred liters following intravenous administration.
Protein Binding of Dronedarone:
The plasma protein binding of Dronedarone and its N-debutyl metabolite is 99.7 % and 98.5 %, respectively. Both of the elements bind with albumin and are not able to saturate.
Metabolism:
Predominantly, Dronedarone undergoes CYP3A-mediated hepatic metabolism. Initially, Dronedarone involves N-debutylation to form N-debutyl Dronedarone which retains 1 of 10 to 1 of 3 of the pharmacological activity of the primary parent compound. N-debutyl Dronedarone metabolizes phenol-dronedarone by dealkylation and propanoic acid dronedarone by oxidative deamination. CYP2D6 can also metabolize Dronedarone to form benzofuran-hydroxyl Dronedarone. Some of the other metabolites include C-dealkyl-dronedarone and dibutylamine-hydroxyl Dronedarone.
Route of Elimination:
In cases of oral administration, about 84 % of the labeled dose is excreted in the stool, and almost 6 % is excreted in urine as metabolites. The elimination half-life ranges from 13 hours to 19 hours.
Toxicity:
In oral studies, Dronedarone shows potential toxicity in humans in acute overdose situations. However, monitoring the patient's cardiac rhythm and blood pressure is important. If there are any symptoms, supportive treatment should be started.
Drug Interactions:
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Benzodiazepine: The metabolism of Benzodiazepine can be reduced when it is combined with Dronedarone.
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Abemaciclib: The serum concentration of Abemaciclib increases when combined with Dronedarone.
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Acebutolo: Dronedarone increases acebutolol's bradycardic (decrease in heart rate) activities.
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Aceclofenac: The chances and severity of existing hypertension increase when Dronedarone is combined with Aceclofenac.
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Alprazolam: This drug's metabolism decreases when combined with Dronedarone.
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Azithromycin: The QTc prolongation can be increased when Azithromycin is combined with Dronedarone.
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Cetirizine: The QTc prolongation gets severe when Dronedarone is combined with Cetirizine.
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Ciprofloxacin: It reduces the metabolism of Dronedarone when combined together.
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Dexamethasone: The metabolism of Dronedarone increases when it interacts with the drug Dexamethasone.
Food Interactions of Dronedarone:
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Consumption of grapefruit and its products should be avoided while taking Dronedarone as it increases the concentrations of the drug by three times.
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The herb St. John's Wort should be avoided as it increases the serum concentration of Dronedarone by inducing CYP3A4.
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It is recommended to take the drug with foods rich in fat as it helps to increase drug absorption.
Clinical Trials of Dronedarone:
Trial Done to Prevent Hospitalization or Death of Cases With Atrial Fibrillation (ATHENA):
Objective of the Trial: To evaluate the efficacy of Dronedarone in preventing hospitalization or, in severe cases, death of an individual suffering from atrial fibrillation/ atrial flutter.
Detailed Description of the Trial: This is a multinational, double-blind, randomized, placebo-controlled, multicenter, parallel-group trial that helps to evaluate the effects of Dronedarone compared to placebo in the ratio 1:1 for a minimum duration of treatment of 12 months and followed by a mean duration of 1.75 years of follow-up. Patients included in the study suffered from atrial fibrillation/ flutter or if there is sinus rhythm due to conversion, which occurred either spontaneously or following a procedure such as electro cardioversion or administration of an antiarrhythmic drug. After the randomization trials, all the patients are followed up until the expected study date ends. The last case of atrial fibrillation included in the study will be followed for a year. The follow-up visits are scheduled in a pattern of 7 days, then after 14 days, after a month, and after three months for every three months intervals until the duration of the study ends. At every follow-up visit, the patient is asked about any occurrence of hospitalization or other events since the last follow-up. The study is monitored by DMC (Independent data monitoring committee) for safety, efficacy, and tolerability.
European Trial of Dronedarone in Moderate to Severe Congestive Heart Failure (ANDROMEDA):
Description: This study assessed Dronedarone's tolerability, safety, and efficacy versus placebo in patients suffering from congestive heart failure (CHF) and left ventricular dysfunction (LVD). The trial was randomized with 653 participants. No results were posted for the trial.
Dronedarone in Pregnancy: The medication should not be used in pregnancy as it can harm the development of the fetus in the womb. It is important to mention to the doctor about pregnancy before starting the drug.
Dronedarone and Breastfeeding: It is unknown whether the drug is present in breast milk, but it is recommended not to breastfeed while consuming the drug.
Dronedarone and Older Patients: Older age groups may display sensitivity to several drugs and may have allergies. It is important to state the presence of any allergies in older patients before taking the drug Dronedarone.
Advantages of Dronedarone Over Other Antiarrhythmics: The drug Dronedarone is a new antiarrhythmic and has fewer adverse effects than other antiarrhythmics such as Amiodarone. It reduces the chances of hospitalization compared to Amiodarone.
