Drug Interaction:
Dronedarone is metabolized by CYP 3A and is a moderate inhibitor of CYP 3A
and CYP 2D6 and has potentially important pharmacodynamic interactions
.
Class I or III Antiarrhythmics: contraindicated
.
Digoxin: Consider discontinuation or halve dose of digoxin before treatment
and monitor digoxin levels
.
Calcium channel blockers (CCB): Initiate CCB with low dose and increase
after ECG verification of tolerability
.
Beta-blockers: May provoke excessive bradycardia, Initiate with low dose
and increase after ECG verification of tolerability
.
CYP 3A inducers: Avoid concomitant use
.
Grapefruit juice: Avoid concomitant use
.
Statins: Avoid simvastatin doses greater than 10 mg daily.
Follow label recommendations for concomitant use of other statins
with a CYP 3A and P-gp inhibitor like dronedarone
.
CYP 3A substrates with a narrow therapeutic index (e.g., sirolimus and tacrolimus):
Monitor and adjust dosage of concomitant drug as needed when used with MULTAQ
.
Warfarin: Monitor INR after initiating dronedarone in patients taking warfarin.
Indication:
Proprietary Name- Multaq
Established Name - Dronedarone Hcl
Applicant- Sanofi Aventis
Indication-
Reduce risk of patients with paroxysmal or persistent atrial fubrillation(AF)
or atrial flutter (AFL)
Dosage-
One tablet 400mg twice daily morning and evening
Approved by FDA on 1-7-2009 (Ref- FDA approved List- 2009)
Approved by (DCI) Drug Controller GENERAL - India For Marketing
(Ref- IDMA Publication)
Name of Drug Indication Date of Approval
Dronedarone Hcl 08-04-2010
Film Coated Tablet 400mg
To reduce the risk of Cardiovascular Hospitalization in patients
with proxysmal or persistent Atrial Fibrillation (AF ) or Atrial Flutter (AFL)
with a recent episode of AF /AFL and associated Cardiovascular risk
factors i.e. age > 70 ,hypertension, Diabetes, Prior Cerebrovascular
accident, Left Ventricular Ejection Fraction (LVEF) < 40% , who are in
sinus rhythm or who will be cardioverted
Adverse Reaction:
Most common adverse reactions (.2%) are diarrhea, nausea, abdominal pain,
vomiting, and asthenia
Contra-Indications:
CONTRAINDICATIONS
.
Permanent AF (patients in whom normal sinus rhythm will not or cannot be restored)
(Boxed Warning )
.
Recently decompensated heart failure requiring hospitalization or Class IV heart failure
. (Boxed Warning )
.
Second-or third-degree atrioventricular (AV) block or sick sinus syndrome
(except when used in conjunction with a functioning pacemaker)
.
Bradycardia <50 bpm
.
Concomitant use of a strong CYP3A inhibitor
.
Concomitant use of drugs or herbal products that prolong the QT interval and
may induce Torsade de Pointes
.
Liver or lung toxicity related to the previous use of amiodarone
.
Severe hepatic impairment
.
QTc Bazett interval .500 ms
.
Pregnancy
and Nursing mothers
.
Hypersensitivity to the active substance or to any of the excipients
WARNINGS AND PRECAUTIONS
.
Determine cardiac rhythm at least once every 3 months. If AF is detected discontinue
MULTAQ or cardiovert
.
Ensure appropriate antithrombotic therapy prior to and throughout MULTAQ use
.
Liver injury: if hepatic injury is suspected, discontinue MULTAQ
.
If pulmonary toxicity is confirmed, discontinue treatment
.
Hypokalemia and hypomagnesemia: Maintain potassium and magnesium levels
within the normal range
.
Renal impairment: Monitor renal function periodically
.
Teratogen: Women of childbearing potential should use effective contraception
while using MULTAQ
Dosages/ Overdosage Etc:
INDICATIONS AND USAGE
MULTAQ is an antiarrhythmic drug indicated to reduce the risk of hospitalization for
atrial fibrillation (AF) in patients in sinus rhythm with a history of paroxysmal or persistent AF
-DOSAGE AND ADMINISTRATION
One tablet of 400 mg twice a day with morning and evening meals
DOSAGE FORMS AND STRENGTHS
400 mg film-coated tablets
Patient Information:
1.MULTAQ should be administered with a meal.
2.Warn patients not to take MULTAQ with grapefruit juice.
3.If a dose is missed, patients should take the next dose at the regularly
scheduled time and should not double the dose.
4.Advise patients to consult a physician before stopping treatment with MULTAQ.
5.Advise patients to consult a physician if they develop signs or symptoms
of heart failure such as acute weight gain, dependent edema, or increasing
shortness of breath.
6.Advise patients to immediately report any symptoms of potential liver injury
(such as anorexia, nausea, vomiting, fever, malaise, fatigue, right upper
quadrant abdominal discomfort, jaundice, dark urine or itching) to their physician.
7.Advise patients to inform their physician of any history of heart failure,
rhythm disturbance other than atrial fibrillation or flutter or predisposing conditions
such as uncorrected hypokalemia.
8.MULTAQ may interact with some drugs; therefore, advise patients to report to
their doctor the use of any other prescription, non-prescription medication
or herbal products, particularly St. John’s wort.
Pharmacology/ Pharmacokinetics:
Mechanism of Action
The mechanism of action of dronedarone is unknown. Dronedarone has antiarrhythmic
properties belonging to all four Vaughan-Williams classes, but the contribution
of each of these activities to the clinical effect is unknown.
Pharmacokinetics
Dronedarone is extensively metabolized and has low systemic bioavailability;
its bioavailability is increased by meals. Its elimination half life is 13-19 hours.
Pregnancy and lactation:
Pregnancy
Pregnancy Category X
MULTAQ may cause fetal harm when administered to a pregnant woman. In animal studies,dronedarone was teratogenic in rats at the maximum recommended human dose (MRHD), and in If this drug is used during pregnancy or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
Nursing Mothers
It is not known whether MULTAQ is excreted in human milk. Dronedarone and its metabolites are excreted in rat milk. During a pre-and post-natal study in rats, maternal dronedarone administration was associated with minor reduced
body-weight gain in the offspring.
Because many drugs are excreted in human milk and because of the potential for
serious adverse reactions in nursing infants from MULTAQ, discontinue nursing
or discontinue the drug
Pediatric Use
Safety and efficacy in children below the age of 18 years have not been established.
Geriatric Use
More than 4500 patients with AF or AFL aged 65 years or above were included in
the MULTAQ clinical program (of whom more than 2000 patients were 75 years or older).
Efficacy and safety were similar in elderly and younger patients.
Manufacturer Details