Multaq (Dronaderone) is a noniodinated congener of amiodarone. It is an anti-arrhythmic drug that is indicated in patients with paroxysmal atrial fibrillation who are currently in sinus rhythm.

Multaq (Dronaderone) Uses:

• Paroxysmal or persistent atrial fibrillation:

  • To minimize the risk of hospitalization for atrial fibrillation (AF) in patients in sinus rhythm with a prior history of paroxysmal or persistent atrial fibrillation

• Off Label Use of Dronedarone in Adults:

  • Alternative antiarrhythmic for the treatment of atrial fibrillation in patients with hypertrophic cardiomyopathy (HCM).

FDA Dronaderone prescribing information can be viewed here: Dronaderone

Multaq (Dronaderone) Dose in Adults

Note:

• Before starting dronedarone, class I or III antiarrhythmics (eg, amiodarone, flecainide, propafenone, quinidine, disopyramide, dofetilide, sotalol) or drugs that are strong inhibitors of CYP3A  (eg, ketoconazole, itraconazole, voriconazole, cyclosporine, telithromycin, clarithromycin, nefazodone, and ritonavir) should be withheld.

Multaq (Dronaderone) Dose in the treatment of Paroxysmal or persistent atrial fibrillation:

Note:

• For patients in normal sinus rhythm with a history of paroxysmal or persistent atrial fibrillation;
• It must not be used for patients in permanent atrial fibrillation to control ventricular rate; should not be used in patients with symptomatic heart failure, within 4 weeks decompensated heart failure needed hospitalization or NYHA Class III or IV symptoms.
• 400 mg orally twice daily with meals.

Use in Children:

Not indicated. 

Pregnancy Risk Factor X

• Studies on animals have shown that fetal abnormalities are contraindicated during pregnancy.
• Women may also become pregnant if they do not see the evidence.

Dronedarone use during breastfeeding:

• It is not known if dronedarone is present in breast milk.
• The manufacturer has declared that breast-feeding is not recommended due to the risk of serious side effects in the infant.

Dose in Kidney disease:

No dosage adjustment is needed.

Dose in Liver disease:

• Mild to moderate impairment:
  • No dosage adjustment needed.
• Severe impairment:
  • Use is contraindicated.

Common Side Effects of Multaq (Dronaderone):

• Cardiovascular:

  • Prolonged Q-T Interval On ECG

• Renal:

  • Increased Serum Creatinine

Less Common Side Effects Of Multaq (Dronaderone):

• Cardiovascular:

  • Bradycardia

• Dermatologic:

  • Allergic Dermatitis
  • Dermatitis
  • Eczema
  • Pruritus
  • Skin Rash

• Gastrointestinal:

  • Diarrhea
  • Nausea
  • Abdominal Pain
  • Dyspepsia
  • Vomiting

• Neuromuscular & Skeletal:

  • Weakness

Contraindications to Multaq (Dronaderone):

• Hypersensitivity to dronedarone and any component of the formula
• Permanent atrial fibrillation is a condition that affects patients whose normal sinus rhythm can't be restored.
• Symptomatic heart failure (heart disease with decompensation that requires hospitalization, NYHA Class III symptoms or IV symptoms in the past 4 weeks).
• Lung or liver toxicities due to previous amiodarone usage.
• Second- or third-degree atrioventricular blocks or sick sinus syndromes (except when used in conjunction with an artificial pacemaker).
• bradycardia <50 beats per minute.
• Concurrent use of strong CYP3A4 inhibitors (eg, itraconazole or voriconazole), cyclosporine and telithromycin.
• Concurrent use of herbal or other drugs that may prolong the QT interval can increase the risk of torsade.
• QT interval >=500msec or PR interval>280msec
• Grave hepatic dysfunction.
• pregnancy.
• Breast-feeding

Canadian labeling: Additional contraindications not in US labeling

• If sinus rhythm is not restored, permanent atrial fibrillation cannot be sustained for any length of time. Further attempts to restore it should be abandoned.
• An independent NYHA class that has a history or current diagnosis of heart failure;
• Systolic dysfunction of the left ventricular left ventricle
• Distal block, complete bundle branch block, sinus dysfunction or atrial conduction defect (except when used in conjunction with a working pacemaker);
• Hemodynamic instability

Warnings and precautions

• Heart failure (HF):

  • There have been cases of HF symptoms that are either new-onset or worsening.
  • Withhold dronedarone if the patient experiences new or worsening HF symptoms, such as weight gain, dependent edema or worsening shortness or breath.

• Hepatic effects

  • There have been cases of severe liver injury and even acute liver failure that led to liver transplantation.
  • Withhold therapy is recommended for suspected liver injury.
  • If liver injury is confirmed, it is important to immediately start appropriate treatment.
  • Patients should be advised to notify the doctor if they experience any symptoms of hepatic injuries (anorexia and malaise, fatigue or jaundice, dark urine. itching, right quadrant pain, nausea, vomiting, abdominal pain and/or fever).
  • You should monitor serum liver enzymes and levels of bilirubin regularly, particularly during the first six months of treatment.

• Extendation of the QT interval:

  • Dronedarone can cause a mild prolongation in the QT interval (averaged 10msec); however, other effects have been reported to be much more severe.
  • Patients with QT intervals >=500msec are not recommended to use dronedarone.

• Effects on the renal system:

  • Dronedarone can cause slightly higher serum creatinine (0.1 mg/dL), within seven days of starting. This is due to inhibition of tubular secretion. However, glomerular filter rate is not affected.
  • The effect can be reversed by stopping.
  • Prerenal azotemia, markedly elevated serum creatinine and acute renal failure were all observed. This was often in the context of hypovolemia or heart failure.
  • With appropriate medical treatment, the effects can be reversed. Monitor your renal function regularly to determine if you have any side effects.
  • Contraindicated for heart failure

• Respiratory effects

  • There have been reports of interstitial lung disease, including pulmonary fibrosis (and pneumonitis).
  • Assess patients who experience dry cough or shortness of breathing to rule out pulmonary toxicology.
  • Stop treatment if pulmonary toxicity is confirmed.
  • Amiodarone is contraindicated for pulmonary toxicities.

• Cardiac devices (eg, implanted defibrillators):

  • A trial in which dronedarone was administered during ischemia in a porcine model showed that it does not alter the threshold for implantable cardioverter-defibrillators' (ICD) defibrillation. This is in contrast to amiodarone.
  • These results will need to be confirmed in humans by human studies.
  • Assess the threshold for defibrillation when you start dronedarone or during therapy.

• Electrolyte imbalance:

  • Before and during therapy, correct electrolyte disturbances (hypokalemia and hypomagnesemia).

• Heart failure (HF): [US Boxed Warning]:

  • In decompensated cardiac failure, contraindicated
  • Patients with symptomatic heart failure (HF) with recent decompensation that requires hospitalization or NYHA Class IV symptoms are at double the risk of dying.
  • Canadian labeling prohibits the use dronedarone in patients who have had or are currently suffering from heart failure. This is independent of NYHA class.

• Hepatic impairment

  • Patients with mild to moderate liver dysfunction should be cautious; severe hepatic impairment is contraindicated.
  • Patients with liver damage from amiodarone are not advised to use it.

• Permanent atrial fibrillation: [US Boxed Warn]

  • Permanent atrial fibrillation is contraindicated. This doubles the risk for death, stroke (especially in the first 2 weeks) and hospitalization due to heart failure.
  • Patients with permanent AF should not be used if they are unable to convert to normal sinus rhythm.
  • At least once every three months, monitor your ECG.
  • Patients who are in AF (if medically indicated) or withhold dronedarone may be Cardiovert.

Monitoring parameters:

• ECG (at least every 3 months)
• blood pressure, heart rate, and rhythm throughout treatment.
• assess patient for signs of new or worsening heart failure and liver injury (eg, jaundice, dark urine, anorexia, nausea, itching, fatigue, right upper quadrant pain, fever).
• monitor serum electrolytes (especially potassium and magnesium), periodically monitor serum liver enzymes and bilirubin (especially during the first 6 months of therapy)

Patients with implantable cardiac devices:

• Monitor pacing or defibrillation thresholds.

Canadian labeling: Additional monitoring recommendations:

• ECG at least every 6 months during treatment;
• serum creatinine 1 week after beginning therapy followed by periodic renal function tests;
• periodic pulmonary function assessment

How to administer Multaq (Dronaderone)?

Administer orally with breakfast and dinner.

Mechanism of action of Multaq (Dronaderone):

• Non-iodinated antiarrhythmic drug structurally related to Amiodarone, with properties from all four antiarrhythmic classes.
• Dronedarone blocks sodium (INa), potassium (IKr and IKI, IKAch and Isus) channels, prolonging the action potential and refractory time in myocardial tissues without any reverse-use dependent effects.
• It decreases AV conduction and sinus function by inhibiting calcium (ICaL), channels, and beta-receptor blocking activities.
• Dronedarone is similar to amiodarone in that it also inhibits alpha-1 receptor mediated rises in blood pressure

Protein binding:

• >98%

Metabolism:

• Hepatic via CYP3A4 to active N-debutyl metabolite (1/10 to 1/3 as potent as dronedarone) and other inactive metabolites

Bioavailability:

• Without food: 4%;
• With high-fat meal: 15%

Half-life elimination:

• 13 to 19 hours

Time to peak, plasma:

• 3 to 6 hours

Excretion:

• Feces (84% mainly as metabolites);
• urine (~6% mainly as metabolites)

International Brands of Dronedarone:

• Multaq
• Dronadex
• Globadrone
• Regivas
• Ritmodex
• Vasodarone

Dronedarone Brands Names in Pakistan:

No Brands Available in Pakistan.