Product Information
Registration Status: ActiveOTEZLA TABLET STARTER PACK is approved to be sold in Singapore with effective from 2017-03-29. It is marketed by CELGENE PTE LTD, with the registration number of SIN15202P.
This product contains Apremilast 10mg in the form of TABLET, FILM-COATED. It is approved for ORAL use.
This product is manufactured by Celgene International Sarl in SWITZERLAND, andPatheon Inc in CANADA.
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
Apremilast is a novel, orally available small molecule inhibitor of type-4 cyclic nucleotide phosphodiesterase (PDE-4). It is indicated in the treatment of active psoriatic arthritis in adults (approved by the FDA in March 2014) and moderate to severe plaque psoriasis (approved by the FDA in September 2014). PDE-4 is a cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase that is predominantly located in inflammatory cells. By inhibiting PDE-4, apremilast increases intracellular levels of cAMP and thereby inhibits the production of multiple proinflammatory mediators including PDE-4, TNF-alpha, interleukin-2 (IL-2), interferon-gamma, leukotrienes, and nitric oxide synthase. By targeting a central component of the inflammatory signaling cascade rather than a single inflammatory marker, PDE-4 inhibition may restore the homeostatic balance between pro- and anti-inflammatory signalling.
Indication
Investigated for use/treatment in psoriasis and psoriatic disorders.
Mechanism of Action
Apremilast is a novel, orally available small molecule inhibitor of type-4 cyclic nucleotide phosphodiesterase (PDE-4). PDE-4 is a cyclic adenosine monophosphate (cAMP)-specific phosphodiesterase that is predominantly located in inflammatory cells. By inhibiting PDE-4, apremilast increases intracellular levels of cAMP and thereby inhibits the production of multiple proinflammatory mediators including PDE-4, TNF-alpha, interleukin-2 (IL-2), interferon-gamma, leukotrienes, and nitric oxide synthase. By targeting a central component of the inflammatory signaling cascade rather than a single inflammatory marker, PDE-4 inhibition may restore the homeostatic balance between pro- and anti-inflammatory signalling.
Pharmacokinetics
- Absorption
- When taken orally, apremilast is absorbed with an absolute bioavailability of ~73%. Co-administration with food does not alter the extent of absorption.
- Distribution
- Peak plasma concentrations (Cmax) occur at a median time (tmax) of ~2.5 hours.
- Metabolism
- Apremilast is metabolized via multiple pathways, including cytochrome (CYP) 3A4-mediated oxidative metabolism with subsequent glucuronidation, non-enzymatic hydrolysis, and non-CYP3A4-mediated metabolism. The unchanged drug accounts for 45% of circulating radioactivity and <7 % of excreted radioactivity. The main metabolite of apremilast is O-desmethyl apremilast glucuronide (M12), with nine other minor metabolites all with at least 50-fold less potency than apremilast in inhibiting PDE-4 and TNF-a.
- Elimination
Clearance
10 L/hr.
Toxicity
DEPRESSION AND SUICIDE: Apremilast has been associated with increased depression and suicidal behaviour in patients. WEIGHT LOSS: Apremilast has been associated with weight decrease in patients.
Active Ingredient/Synonyms
Apremilast | Aprémilast | Apremilastum | N-{2-[(1S)-1-(3-Ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}acetamide | Apremilast |
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.