Product Information
Registration Status: ActiveMULTAQ FILM-COATED TABLET 400MG is approved to be sold in Singapore with effective from 2010-08-20. It is marketed by SANOFI-AVENTIS SINGAPORE PTE LTD, with the registration number of SIN13849P.
This product contains Dronedarone 400mg in the form of TABLET, FILM-COATED. It is approved for ORAL use.
This product is manufactured by Sanofi Winthrop Industrie in FRANCE.
It is a Prescription Only Medicine that can only be obtained from a doctor or a dentist, or a pharmacist with a prescription from a Singapore-registered doctor or dentist.
Description
Dronedarone is a sinus rhythm controller for management of paroxysmal or persistent atrial fibrillation. Classified as a Class III antiarrhythmic but displays properties of all four Vaughan-Williams classes, dronedarone blocks a multitude of channels (sodium, potassium, calcium), and demonstrates antiadrenergic properties. Chemically, it is a benzofuran derivative. FDA approved on July 1, 2009.
Indication
Management of paroxysmal or persistent atrial fibrillation via restoration of normal sinus rhythm.
Mechanism of Action
The antiarrhythmic effect of dronedarone may be due to at least two major actions. It prolongs the duration of action potential and refractory period in myocardial tissue via inhibition of sodium and potassium channels. Via inhibition of calcium channels and blockage of beta1-adrenergic receptors, a decrease in AV conduction and sinus node function can be observed. Dronedarone can also cause an increase in blood pressure by inhibition of alpha1-adrenergic receptors.
Pharmacokinetics
- Absorption
- Because of presystemic first pass metabolism the absolute bioavailability of dronedarone without food is low, about 4%. It increases to approximately 15% when dronedarone is administered with a high fat meal. After oral administration in fed conditions, peak plasma concentrations of dronedarone and the main circulating active metabolite (N-debutyl metabolite) are reached within 3 to 6 hours. After repeated administration of 400 mg twice daily, steady state is reached within 4 to 8 days of treatment. The steady state Cmax and exposure of the main N-debutyl metabolite is similar to that of the parent compound.
- Distribution
- When intravenously administered, the volume of distribution is 1400 L.
- Metabolism
- Majority of dronedarone is eliminated by first-pass metabolism in the liver by CYP3A4 enzymes (>84%). Dronedarone is also metabolized by CYP2D6 to a lesser extent. N-DBD is its active metabolite (1/10 to 1/3 potency of dronedarone) which can penetrate the blood-brain barrier, placenta, and is excreted in breast milk. However, it does not significantly accumulate in plasma or tissue.
- Elimination
Clearance
Plasma clearance = 130-150 L/h.
Toxicity
Most common adverse reactions (≥2%) are diarrhea, nausea, abdominal pain, vomiting, and asthenia.
Active Ingredient/Synonyms
N-(2-Butyl-3-(4-(3-(dibutylamino)propoxy)benzoyl)-5-benzofuranyl)-methanesulfonamide | N-(2-Butyl-3-(P-(3-(dibutylamino)propoxy)benzoyl)-5-benzofuranyl)methanesulfonamide | SR 33589 | SR 33589b | Dronedarone |
Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.