Product Details Regulatory status Exclusivity Data Drug product labeling API information API MSDS Formulation information OGD Details OB Listed Patents Packaging details Drug product assessment reports Global sales API reference Price Listed Dossier
Product Details
Active Ingredient: APREMILAST 
Proprietary Name: OTEZLA 
Dosage Form; Route of Administration: TABLET; ORAL 
Strength: 10MG, 20 MG, 30 MG
Reference Listed Drug: 10MG, 20 MG, 30 MG
Reference Standard: 30 MG
TE Code:  NA
Application Number: N205437 
Approval Date: Mar 21, 2014 
Applicant Holder Full Name: CELGENE CORP 
Marketing Status:  Prescription 
Regulatory status
Approval in different country:
US FDA: Mar 21, 2014 
EMA: Jan 15, 2015
Health Canada: Nov 12, 2014
Australia: 12 March 2015
Exclusivity Data
Exclusivity Code (Expiration): NCE (03/21/2019)

Drug product labeling INDICATIONS AND USAGE
OTEZLA, an inhibitor of phosphodiesterase 4 (PDE4), is indicated for the treatment of:
· Adult patients with active psoriatic arthritis
 · Patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy
DOSAGE AND ADMINISTRATION
· To reduce risk of gastrointestinal symptoms, titrate to recommended dose of 30 mg twice daily according to the following schedule
§ Day 1: 10 mg in morning
§ Day 2: 10 mg in morning and 10 mg in evening
§ Day 3: 10 mg in morning and 20 mg in evening
§ Day 4: 20 mg in morning and 20 mg in evening
§ Day 5: 20 mg in morning and 30 mg in evening
§ Day 6 and thereafter: 30 mg twice daily
· Dosage in Severe Renal Impairment:
§ Recommended dose is 30 mg once daily
§ For initial dosage titration, titrate using only morning schedule listed in Table 1 and skip afternoon doses
API information
STRUCTURE

Chemical Name: N-[2-[(1S)-1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-2,3-dihydro-1,3-dioxo-1H-isoindol-4-yl]acetamide
Molecular Formula: C22H24N2O7S
Molecular Weight: 460.5
Appearance: a white to pale-yellow powder
Hygroscopic: non hygroscopic
Melting Point: 156.1°C
Solubility: It is practically insoluble in aqueous buffers irrespective of pH range, soluble in acetone, acetonitrile, methylethylketone, methylene chloride and tetrahydrofuran.
BCS Class: IV
Polymorphism: Polymorphism has been observed for apremilast and seven polymorphic forms (designated A-G) of the active substance were identified. The desired form B was found to be the most thermodynamically stable anhydrous form of apremilast. The manufacturing process consistently yields active substance of single crystal form B.
pKa (Strongest Acidic): 4.83 (Predicted)
pKa (Strongest Basic): (Predicted) -0.25
Log P: 1.79 (Predicted)
CAS No: 1258597-46-4
API MSDS
Click here for Download MSDS of Apremilast
Formulation information Composition:
10 mg
Core tablets:
Lactose monohydrate (60 mg), microcrystalline cellulose (26.25 mg), croscarmellose sodium (3 mg), magnesium stearate (0.75 mg)
Coating:
Opadry II pink (polyvinyl alcohol - 40% titanium dioxide - 24.6%, macrogol - 20.2% talc - 14.8% iron oxide red dye (E172) - 0 , 4%) - 4 mg
20 mg
Core tablets:
Lactose monohydrate (120 mg), microcrystalline cellulose (52.5 mg), croscarmellose sodium (6 mg), magnesium stearate (1.5 mg)
Coating:
Opadry II brown (polyvinyl alcohol - 40% titanium dioxide - 12.13%, macrogol - 20.2% talc - 14.8% iron oxide red dye (E172) - 1 22% iron oxide yellow dye (E172) - 11.65) - 8 mg
30 mg
Core tablets:
Lactose monohydrate (180 mg), microcrystalline cellulose (78.75 mg), croscarmellose sodium (9 mg), magnesium stearate (2.25 mg)
Coating:
Opadry II beige (polyvinyl alcohol - 40% titanium dioxide - 22.99% Macrogol - 20.2% talc - 14.8% iron oxide red dye (E172) - 1 18% colorant ferric oxide yellow (E 172) - 0.43%, the dye black iron oxide (E172) - 0.4) - 12 mg

Manufacturing process details:
The manufacturing process consists of three main steps: i) blending and lubrication process, ii) compression process and iii) coating process. The process is considered to be a standard manufacturing process.

Tablet Details
Parameters
10 mg
20 mg
30 mg
Description
Pink, diamond shaped film-coated tablet with “APR” engraved on one side and “10” on the opposite side
Brown, diamond shaped film-coated tablet with “APR” engraved on one side and “20” on   the opposite side
Beige, diamond shaped film-coated tablet with “APR” engraved on one side and “30” on the opposite side
Tablet Image






Tablet Dimension
8 mm
10 mm
12 mm

OGD Details
Apparatus: USP type II
Speed: 60 RPM
Volume: 900 mL
Medium: 0.15% SLS in 25 mM Sodium Phosphate Buffer, pH 6.8
Time point (min):10, 15, 20, 30, and 45
Updated date: May 18, 2017
OB Listed Patents
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Packaging details
Market
10 mg
20 mg
30 mg
US
Two-week starter pack:
13-tablet blister titration pack containing: (4) 10-mg, (4) 20-mg, and (5) 30-mg tablets with an additional (14) 30 mg tablets
Bottles of 60
Two-week starter pack:
13-tablet blister titration pack containing: (4) 10-mg, (4) 20-mg, and (5) 30-mg tablets with an additional (14) 30 mg tablets
28-count carton:
Two 30-mg blister cards containing (14) 30-mg tablets
EU
The treatment initiation pack is a folding wallet containing 27 tablets: PVC/aluminium foil blister of 4 x 10 mg + 4 x 20 mg + 19 x 30 mg tablets
The one-month standard pack of PVC/aluminium foil blister of 56 x 30 mg tablets The three-month standard pack of PVC/aluminium foil blister of 168 x 30 mg tablets
Australia 
Blister pack:
56 x 30 mg tablet 168 x 30 mg tablets ‘Titration pack’: 4 x 10 mg + 4 x 20 mg + 19 x 30 mg tablets
Drug product assessment reports
FDA Label
 Click here
Dailymed
Click here 
Summary of product characteristic
 Click here
FDA chemistry review
 Click here
FDA Pharmacology Review(s)
 Click here
FDA Clinical Pharmacology Biopharmaceutics Review(s)
 Click here
FDA BE Recommendation
 Click here
European Public Assessment Report
 Click here
Australia  Public Assessment Report
 Click here

 Global sales U.S. Medicaid: 12.00
Annual Reports: 1017.00
API reference Price $12014/ Kg
Listed Dossier
Applicant
Country of registration
Strengths
Regulatory information
Supporting Details
ALFRED E TIEFENBACHER GmbH & Co KG
GERMANY
10 mg, 20 mg and 30 mg
EU dossier reediness by Q3-2020