Multaq

/ Sanofi

Treatment should be initiated and monitored only under specialist supervision. Treatment with MULTAQ can be initiated in an outpatient setting.
The recommended dose is 400 mg twice daily in adults. It should be taken as
• one tablet with the morning meal and
• one tablet with the evening meal.
Grapefruit juice should not be taken together with MULTAQ.
If a dose is missed, patients should take the next dose at the regular scheduled time and should not double the dose.
Treatment with Class I or III antiarrhythmics (such as flecainide, propafenone, quinidine, disopyramide, dofetilide, sotalol, amiodarone) must be stopped before starting MULTAQ.
There is limited information on the optimal timing to switch from amiodarone to MULTAQ. It should be considered that amiodarone may have a long duration of action after discontinuation due to its long half life. If a switch is envisaged, this should be done under the supervision of a specialist.

For the maintenance of sinus rhythm after successful cardioversion in adult clinically stable patients with paroxysmal or persistent atrial fibrillation (AF). Due to its safety profile, it should only be prescribed after alternative treatment options have been considered. Should not be given to patients with left ventricular systolic dysfunction or to patients with current or previous episodes of heart failure.

Hypersensitivity to the active substance or to any of the excipients. Second- or third- degree AV block, complete bundle branch block, distal block, sinus node dysfunction, atrial conduction defects, or sick sinus syndrome (except when used in conjunction with a functioning pacemaker), bradycardia.

Careful monitoring during dronedarone administration is recommended by regular assessment of cardiac, hepatic and pulmonary function. If AF reoccurs discontinuation of dronedarone should be considered. Monitoring of co-administered drugs like digoxin and anti-coagulants is necessary. It is recommended to perform ECGs serially, at least every 6 months. If patients treated with dronedarone develop permanent AF treatment should be discontinued. Dronedarone is contraindicated in patients in unstable hemodynamic conditions, with history of, or current heart failure or left ventricular systolic dysfunction. Patients should be carefully evaluated for symptoms of CHF. There have been spontaneously reported events of new or worsening heart failure during treatment. Patients should be advised to consult a physician if they develop or experience signs or symptoms of heart failure, such as weight gain, dependent edema, or increased dyspnea. If heart failure develops, treatment should be discontinued. Patients should be followed for the development of left ventricular systolic dysfunction during treatment. If left ventricular systolic dysfunction develops, treatment should be discontinued. Caution is needed in patients with coronary artery disease. Caution is needed in elderly patients ≥ 75 years with multiple co-morbidities. Hepatocellular liver injury, including life-threatening acute liver failure, has been reported. Liver function tests should be performed prior to initiation of treatment with dronedarone after one week and after one month following initiation of treatment and then repeated monthly for six months, at months 9 and 12, and periodically thereafter. If ALT levels are confirmed to be >3 ?ULN, treatment with dronedarone should be withdrawn. Appropriate investigation and close observation of patients should continue until normalization of ALT. Patients should immediately report any symptoms of potential liver injury (such as sustained new-onset abdominal pain, anorexia, nausea, vomiting, fever, malaise, fatigue, jaundice, dark urine or itching) to their physician. An increase in plasma creatinine (mean increase 10 μmol/L) has been observed in healthy subjects and in patients. In most patients this increase occurs early after treatment initiation and reaches a plateau after 7 days. It is recommended to measure plasma creatinine values prior to and 7 days after initiation of dronedarone. If an increase in creatininemia is observed, serum creatinine should be re-measured after a further 7 days. If no further increase in creatinemia is observed, this value should be used as the new reference baseline taking into account that this may be expected with dronedarone. If serum creatinine continues to rise then consideration should be given to further investigation and discontinuing treatment. An increase in creatininemia should not necessarily lead to the discontinuation of treatment with ACE inhibitors or Angiotensin II Receptors Antagonists (AIIRAs). Larger increases in creatinine, including cases of pre-renal azotemia secondary to CHF, hypoperfusion or hypovolemia, after dronedarone initiation. It is unknown whether dronedarone and its metabolites are excreted in human milk. Available pharmacodynamic/toxicological data in animals have shown excretion of dronedarone and its metabolites in milk. A risk to the newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.

The most frequent adverse reactions observed were CHF, bradycardia, diarrhea, nausea and vomiting, abdominal pains, rashes, pruritis, fatigue and asthenia.  For full details see prescribing information.

Dronedarone is primarily metabolised by CYP 3A4. Therefore, inhibitors and inducers of CYP 3A4 have the potential to interact on dronedarone. Dronedarone is a moderate inhibitor of CYP 3A4, a mild inhibitor of CYP 2D6 and a potent inhibitor of P-glycoproteins (P-gp). Dronedarone therefore, has the potential to interact on medicdbinal products substrates of P-glycoproteins, CYP 3A4 or CYP 2D6. Dronedarone has no significant potential to inhibit CYP 1A2, CYP 2C9, CYP 2C19, CYP 2C8 and CYP 2B6. A potential pharmacodynamic interaction can also be expected with beta-blockers, calcium antagonists and digitalis. medicdbinal products inducing torsades de pointes such as phenothiazines, cisapride, bepridil, tricyclic antidepressants, certain oral macrolides (such as erythromycin), terfenadine and Class I and III antiarrhythmics are contraindicated because of the potential risk of proarrhythmia. Caution should also be taken with co-administration with beta-blockers or digoxin. There was a weak interaction between dronedarone and statins transported by OATP, such as rosuvastatin (which resulted in a mean 1.4-fold increase in rosuvastatin exposure).In clinical trials, there was no evidence of safety concerns when dronedarone was co-administered with statins metabolized by CYP 3A4. However, spontaneously reported cases of rhabdomyolysis when dronedarone was given in combination with a statin (simvastatin in particular) have been reported, and, therefore, concomitant use of statins should be undertaken with caution. Dronedarone could increase plasma concentrations of immunosupresants (tacrolimus, sirolimus, everolimus and cyclosporine). Monitoring of their plasma concentrations and appropriate dose adjustment is recommended in case of coadministration with dronedarone.
For full details see prescribing information.

Fertility: Dronedarone was not shown to alter fertility in animal studies.
Pregnancy: There are no or limited amount of data from the use of dronedarone in pregnant women. Studies in animals have shown reproductive toxicity. MULTAQ is not recommended during pregnancy and in women of childbearing potential not using contraception.
Lactation: It is unknown whether dronedarone and its metabolites are excreted in human milk. Available pharmacodynamic/toxicological data in animals have shown excretion of dronedarone and its metabolites in milk. A risk to the newborns/infants cannot be excluded A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from MULTAQ therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
For full details see prescribing information.

It is not known whether dronedarone and/or its metabolites can be removed by dialysis (hemodialysis, peritoneal dialysis, or hemofiltration). There is no specific antidote available. In the event of overdose, treatment should be supportive and directed toward alleviating symptoms.