Restores and maintains sinus rhythms
Important policies for management. Rhythm control helps to improve symptoms and improve the quality of life of patients. In December 2021, china's State Drug Administration (NMPA) approved
Used in sinus rhythm patients with a history of paroxysmal or persistent atrial fibrillation, reducing the risk of hospitalization for atrial fibrillation.
Safety is an important consideration when selecting drugs that maintain sinus rhythm after atrial fibrillation cardioversion. Dronedarone is a deiodized benzofuran derivative belonging to Class III antibodies
Similarly, it has a multi-channel blocking effect, which has inhibitory effects on sodium, potassium, calcium ion channels and β receptors, but the adverse reactions are significantly reduced and the risk of arrhythmias is low. Recently, the mainland has formulated expert recommendations to guide clinicians to better apply Dunadaron.
Recommendations for clinical application
1. Indications and contraindications
It is recommended that dunedarone be used primarily in patients with sinus rhythm with paroxysmal or persistent atrial fibrillation/atrial flutter, reducing recurrence of atrial fibrillation/atrial flutter and reducing the risk of re-hospitalization.
(1) Dronedarone is recommended for the prevention of recurrence of paroxysmal atrial fibrillation and maintenance after the restoration of sinus rhythm in patients with persistent atrial fibrillation/atrial flutter, who do not have severe underlying heart disease and have normal left ventricular systolic function, or with the following conditions:
● Ejection fractions are retained
● Mild nonpathic left ventricular hypertrophy (ultrasound chamber wall thickness<13 mm);
● Stability
● Valvular
(2) Dunedalone is not recommended for maintaining sinus rhythm in patients with atrial fibrillation/atrial flutter with LVEF-reducing heart failure, nor is it recommended for ventricular rate control in patients with long-term persistent atrial fibrillation and patients with permanent atrial fibrillation.
(3) Contraindicated in patients with the following conditions:
● Combined application of drugs that cause prolongation of the QT interval;
● Combined application of strong inhibitors of CYP3A4 (
● Complicated by severe liver damage;
● Severe bradycardia with a heart rate of < 50 beats/min, second- to third-degree atrioventricular block, pathological sinus syndrome (except for implanted pacemakers);
● Previous use of amiodarone has been hepatic or pulmonary toxicity.
2. Recommended dosage
The standard dose of dronedarone is 400 mg twice daily. There is no research basis for whether individualized dose adjustment can be used in special patients, such as advanced age.
3. Monitoring and treatment of adverse reactions
Common adverse effects of dronedarone include gastrointestinal symptoms (
Table 1 Dynadarone medication monitoring process
（1）
(2) Electrolytes: maintain normal blood potassium and blood magnesium levels, according to the patient's clinical situation can be monitored once a month.
(3) Liver function: at least before and after medication for the first and 6 months. If in doubt
(4) Renal function: a slight increase in creatinine level can occur after the administration of dronedarone, mainly due to the inhibition of renal tubular secretion of creatinine, which reaches the platform after 7 days and can be restored after stopping the drug.
(5) Gastrointestinal adverse reactions: The most common adverse reactions of dronedarone are diarrhea (9%), nausea (5%), abdominal pain (4%), vomiting (2%), bradycardia (3%), etc. The most common adverse reactions leading to discontinuation of the drug are gastrointestinal dysfunction (3.2%), which usually does not require treatment, or symptomatic treatment; if the patient is intolerant, discontinuation is recommended.
(6) Pulmonary toxicity: post-marketing reports of taking dronedarone can be seen
4. Conversion with other anti-arrhythmic drugs
Class I and III antiarrhythmic drugs, including amiodarone, flucaramine, propafenone, quinidine,
Medication for special populations
1. Patients with renal insufficiency
Dronedarone is less excreted through the kidneys, and the dose of dronedarone in patients with renal insufficiency does not need to be changed. Dronedarone can cause a mild increase in creatinine and should be monitored during administration.
2. Patients with abnormal liver function
Patients with moderate liver injury do not need to adjust the dose, and patients with severe hepatic insufficiency are contraindicated.
3. Patients with abnormal thyroid function
Dronedarone does not cause thyroid dysfunction and can be used in patients with hyperthyroidism caused by amiodarone.
4. Patients with lung diseases
Patients taking Dunedalone tablets may see interstitial lung disease, including pneumonia and pulmonary fibrosis. Patients with dyspnea or dry cough who may be associated with pulmonary toxicity should be evaluated clinically. If pulmonary toxicity is confirmed, the administration must be discontinued. The use of dronedarone is not recommended for patients with pulmonary toxicity due to the administration of amiodarone.
Drug interactions
Dronedarone is a moderate inhibitor of cytochrome P450 enzyme (CYP) 3A4 and CYP2D6 that inhibits the transport of P-glycoproteins. Dronedarone should be avoided in combination with drugs that prolong the QT interval and potent inhibitors of CYP3A. Drugs metabolized by CYP3A4 should be used with caution when combined with dronedarone.
1. Non-vitamin K antagonists oral anticoagulants (NOACs)
Currently recommended when used in conjunction with Dunedalon, with
2. Non-dihydropyridine calcium antagonists
Verapamil and diltiazem are moderate-potency CYP 3A inhibitors that increase the exposure of dronedarone by 1.4 to 1.7 times. Therefore, a lower dose should be given at the beginning of the combination application, the heart rate should be monitored, and an increase in the dose may be considered if well tolerated.
3. Digoxin
Low doses should be used in combination applications, and care should be taken to closely monitor digoxin concentrations to avoid digoxin overdose or even
4. β receptor blockers
When used in combination with dronedarone, β receptor blockers should be reduced according to heart rate. Regardless of whether patients receive β receptor blockers, dronedarone benefits in reducing hospitalizations for first cardiovascular events or deaths from any cause are similar. Therefore, it should be halved before the combination of drugs, and then gradually increased according to the heart rate.
Table 2 Drugs and recommendations for interaction with dronedarone
Literature index: Sun Yihong, Ma Changsheng, Wu Shulin, et al. Chinese expert recommendations for clinical application of Dunadalong [J] . Chin J Internal Medicine, 2021, 60(12) : 1139-1147.