| Active Ingredient | ESOMEPRAZOLE MAGNESIUM (Capsule) |
|---|
| Drug Name | FDA Application No. | Company | Dosage Form;Route | Strength | RLD Strength | Original Approval or Tentative Approval Date |
Exclusivity Expiration (NCE) |
Exclusivity Expiration (ODE) |
Chemical Type |
Review Classification |
Marketing Status |
TE Code |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| NEXIUM | (NDA) 021153 | ASTRAZENECA PHARMS | CAPSULE, DELAYED REL PELLETS;ORAL | EQ 20MG BASE, EQ 40MG BASE | EQ 40MG BASE | February 20, 2001 | _ | _ | 2 New active ingredient | _ | Prescription | AB |
| Parameters | Details |
|---|---|
| Structural Formula |
/Structural_Formula.jpg) |
| Chemical Name | bis(5-methoxy-2-[(S)-[(4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole-1-yl) magnesium trihydrate. |
| CAS No | 119141-88-7 |
| Molecular Formula | C 17H18 N3 O3 S)2 Mg x 3 H 2 O |
| Molecular Weight | 767.2 as a trihydrate and 713.1 on an anhydrous basis |
| Appearance | White to slightly colored crystalline powder |
| Solubility | - |
| Water Solubility | Slightly soluble in water |
| Polymorphism | - |
| pKa (Strongest Acidic) | 9.68 (Predicted) |
| pKa (Strongest Basic) | 4.77 (Predicted) |
| Log P | 0.6 |
| Identification | - |
| Degradation | The stability of esomeprazole magnesium is a function of pH; it rapidly degrades in acidic media, but it has acceptable stability under alkaline conditions. At pH 6.8 (buffer), the half-life of the magnesium salt is about 19 hours at 25°C and about 8 hours at 37°C. |
| Hygroscopic | - |
| Photostability study | - |
| Melting Point | 155 °C |
| BCS Class | - |
| Manufacture of API | - |
| Parameters | Details |
|---|---|
| Indications and Usage | NEXIUM is a proton pump inhibitor indicated for the following: • Treatment of gastroesophageal reflux disease (GERD) • Risk reduction of NSAID-associated gastric ulcer • H. pylori eradication to reduce the risk of duodenal ulcer recurrence • Pathological hypersecretory conditions, including Zollinger-Ellison syndrome |
| Dosage and Administration | 1 month to less than 1 year: 2.5 mg, 5 mg or 10 mg (based on weight). Once daily, up to 6 weeks for erosive esophagitis (EE) due to acid-mediated GERD only. (Refer PIL) |
| Mechanism of action | Esomeprazole is a proton pump inhibitor that suppresses gastric acid secretion by specific inhibition of the H+/K+-ATPase in the gastric parietal cell. The S- and R-isomers of omeprazole are protonated and converted in the acidic compartment of the parietal cell forming the active inhibitor, the achiral sulphenamide. By acting specifically on the proton pump, esomeprazole blocks the final step in acid production, thus reducing gastric acidity. This effect is dose-related up to a daily dose of 20 to 40 mg and leads to inhibition of gastric acid secretion. |
| Absorption |
NEXIUM Delayed-Release Capsules and NEXIUM For Delayed-Release Oral Suspension contain a bioequivalent enteric-coated granule formulation of esomeprazole magnesium. Bioequivalency is based on a single dose (40 mg) study in 94 healthy male and female volunteers under fasting condition. After oral administration peak plasma levels (C max ) occur at approximately 1.5 hours (Tmax ). The C max increases proportionally when the dose is increased, and there is a three-fold increase in the area under the plasma concentration-time curve (AUC) from 20 to 40 mg. At repeated once-daily dosing with 40 mg, the systemic bioavailability is approximately 90% compared to 64% after a single dose of 40 mg. The mean exposure (AUC) to esomeprazole increases from 4.32 µmol*hr/L on Day 1 to 11.2 µmol*hr/L on Day 5 after 40 mg once daily dosing. The pharmacokinetic profile of NEXIUM was determined in 36 patients with symptomatic gastroesophageal reflux disease following repeated once daily administration of 20 mg and 40 mg capsules of NEXIUM over a period of five days. |
| Food Effect | The AUC after administration of a single 40 mg dose of NEXIUM is decreased by 43% to 53% after food intake compared to fasting conditions. NEXIUM should be taken at least one hour before meals. |
| Distribution | Esomeprazole is 97% bound to plasma proteins. Plasma protein binding is constant over the concentration range of 2 to 20 µmol/L. The apparent volume of distribution at steady state in healthy volunteers is approximately 16 L. |
| Metabolism | Esomeprazole is extensively metabolized in the liver by the cytochrome P450 (CYP) enzyme system. The metabolites of esomeprazole lack antisecretory activity. The major part of esomeprazole’s metabolism is dependent upon the CYP 2C19 isoenzyme, which forms the hydroxy and desmethyl metabolites. The remaining amount is dependent on CYP 3A4 which forms the sulphone metabolite. CYP 2C19 isoenzyme exhibits polymorphism in the metabolism of esomeprazole, since some 3% of Caucasians and 15 to 20% of Asians lack CYP 2C19 and are termed Poor Metabolizers. At steady state, the ratio of AUC in Poor Metabolizers to AUC in the rest of the population (Extensive Metabolizers) is approximately 2. Following administration of equimolar doses, the S- and R-isomers are metabolized differently by the liver, resulting in higher plasma levels of the S-than of the R-isomer. |
| Elimination | The plasma elimination half-life of esomeprazole is approximately 1 to 1.5 hours. Less than 1% of parent drug is excreted in the urine. Approximately 80% of an oral dose of esomeprazole is excreted as inactive metabolites in the urine, and the remainder is found as inactive metabolites in the feces. |
| Peak plasma time (Tmax) | 1.5 hours |
| Half life | 1 to 1.5 hours |
| Bioavailability | 90% |
| Age, gender | The AUC and C max values were slightly higher (13%) in females than in males at steady state. Dosage adjustment based on gender is not necessary. |
| DMF | Status | Type | Submit Date | Holder |
|---|---|---|---|---|
| 17278 | I | II | March 31, 2004 | DR REDDYS LABORATORIES LTD |
| 18559 | A | II | August 3, 2005 | SUN PHARMACEUTICAL INDUSTRIES LTD |
| 18821 | A | II | September 28, 2005 | CIPLA LTD |
| 19192 | A | II | February 21, 2006 | DR REDDYS LABORATORIES LTD |
| 20457 | A | II | April 13, 2007 | LUPIN LTD |
| 21375 | I | II | May 23, 2008 | JUBILANT ORGANOSYS LTD |
| 22335 | A | II | December 7, 2010 | JUBILANT GENERICS LTD |
| 22363 | A | II | December 29, 2008 | CADILA HEALTHCARE LTD |
| 22376 | A | II | December 31, 2008 | DR REDDYS LABORATORIES LTD |
| 23110 | A | II | September 14, 2009 | TORRENT PHARMACEUTICALS LTD |
| 23120 | A | II | September 16, 2009 | MYLAN LABORATORIES LTD |
| 23379 | A | II | December 16, 2009 | HETERO DRUGS LTD |
| 23994 | A | II | July 26, 2010 | DR REDDYS LABORATORIES LTD |
| 24338 | A | II | November 12, 2010 | GLENMARK PHARMACEUTICALS LTD |
| 24348 | A | II | November 8, 2010 | HETERO DRUGS LTD |
| 24746 | A | II | March 11, 2011 | DR REDDYS LABORATORIES LTD |
| 24901 | A | II | April 20, 2011 | FIS FABBRICA ITALIANA SINTETICI SPA |
| 25049 | A | II | June 9, 2011 | PCAS |
| 25080 | I | II | April 20, 2011 | FIS FABBRICA ITALIANA SINTETICI SPA |
| 25858 | A | II | March 30, 2012 | DR REDDYS LABORATORIES LTD |
| 26239 | A | II | August 1, 2012 | AUROBINDO PHARMA LTD |
| 26938 | A | II | February 14, 2014 | GLENMARK PHARMACEUTICALS LTD |
| 27251 | A | II | September 17, 2013 | CADILA HEALTHCARE LTD |
| 27472 | A | II | September 17, 2013 | RAKS PHARMA PVT LTD |
| 27639 | A | II | October 31, 2013 | TORRENT PHARMACEUTICALS LTD |
| 27918 | A | II | April 8, 2014 | HEC PHARM CO LTD |
| 27925 | A | II | January 17, 2014 | METROCHEM API PRIVATE LTD |
| 27954 | A | II | March 13, 2014 | MYLAN LABORATORIES LTD |
| 28053 | A | II | March 29, 2014 | JUBILANT GENERICS LTD |
| 28054 | A | II | March 29, 2014 | JUBILANT GENERICS LTD |
| 28127 | A | II | March 31, 2014 | DR REDDYS LABORATORIES LTD |
| 28135 | A | II | March 31, 2014 | DR REDDYS LABORATORIES LTD |
| 28163 | A | II | March 27, 2014 | PERRIGO API LTD |
| 28357 | A | II | June 5, 2014 | HETERO DRUGS LTD |
| 28462 | A | II | July 8, 2014 | MINAKEM |
| 28523 | A | II | December 2, 2014 | MACLEODS PHARMACEUTICALS LTD |
| 28548 | A | II | July 3, 2014 | SHOUGUANG FUKANG PHARMACEUTICAL CO LTD |
| 28581 | A | II | October 1, 2014 | ALKEM LABORATORIES LTD |
| 28777 | A | II | October 21, 2014 | HETERO DRUGS LTD |
| 29389 | A | II | May 30, 2015 | AUROBINDO PHARMA LT |
| 29403 | A | II | July 17, 2015 | RAKS PHARMA PVT LTD |
| 29639 | A | II | September 1, 2015 | CIPLA LTD |
| 29992 | A | II | November 4, 2015 | ZHEJIANG JINHUA CONBA BIO PHARM CO LTD |
| 30020 | A | II | December 10, 2015 | MACLEODS PHARMACEUTICALS LTD |
| 30076 | A | II | December 31, 2015 | MSN LIFE SCIENCES PRIVATE LTD |
| 30401 | A | II | March 30, 2016 | MSN LIFE SCIENCES PRIVATE LTD |
| Parameters | Details | ||
|---|---|---|---|
| Strength | 40 MG | 20 MG | |
| Excipients used |
Glyceryl monostearate 40-55, hydroxypropyl cellulose, hypromellose, magnesium stearate, methacrylic acid copolymer type C, polysorbate 80, sugar spheres, talc, and triethyl citrate |
||
| Composition of coating material | - | ||
| Composition of caspule shell |
Gelatin, FD&C Blue #1, FD&C Red #40, D&C Red #28, titanium dioxide, shellac, ethyl alcohol, isopropyl alcohol, n-butyl alcohol, propylene glycol, sodium hydroxide, polyvinyl pyrrolidone, and D&C Yellow #10. |
||
| Pharmaceutical Development |
Each delayed-release capsule contains 20 mg, or 40 mg of esomeprazole (present as 22.3 mg, or 44.5 mg esomeprazole magnesium trihydrate). |
||
| Manufacture of the product | - | ||
| Tablet / Capsule Image |
/40 MG.jpg)
|
/20 MG.jpg)
|
|
| Appearance | Opaque, hard gelatin, amethyst colored capsules with three radial bars in yellow on the cap and NEXIUM 40 mg in yellow on the body | Opaque, hard gelatin,amethyst colored capsules with two radial bars in yellow on the cap and NEXIUM 20 mg in yellow on the body | |
| Imprint code / Engraving / Debossment | Amethyst colored capsules with three radial bars in yellow on the cap and NEXIUM 40 mg in yellow on the body | Amethyst colored capsules,Two radial bars in yellow on the cap and NEXIUM 20 mg in yellow on the body | |
| Score | No score | No score | |
| Color | Opaque, | Opaque | |
| Shape | Capsule | Capsule | |
| Dimension | 14 mm | 14 mm | |
| Mfg by | - | ||
| Mfg for | - | ||
| Marketed by | - | ||
| Distributed by | AstraZeneca LP | ||
| Application No. | Prod No | Patent No | Patent Expiration | Drug Substance Claim | Drug Product Claim | Patent Use Code | Delist Requested | Link |
|---|---|---|---|---|---|---|---|---|
| N021153 | 1 | 5714504*PED | August 3, 2015 | - | - | - | - | Download |
| N021153 | 1 | 5900424 | May 4, 2016 | Y | - | U - 373 | - | Download |
| N021153 | 1 | 5900424 | May 4, 2016 | Y | - | U - 373 | - | Download |
| N021153 | 1 | 5900424 | May 4, 2016 | Y | - | U - 373 | - | Download |
| N021153 | 1 | 5900424*PED | November 4, 2016 | - | - | - | - | Download |
| N021153 | 1 | 6147103 | October 9, 2018 | - | - | - | - | Download |
| N021153 | 1 | 6147103*PED | April 9, 2019 | - | - | - | - | Download |
| N021153 | 1 | 6166213 | October 9, 2018 | - | - | - | - | Download |
| N021153 | 1 | 6166213*PED | April 9, 2019 | - | - | - | - | Download |
| N021153 | 1 | 6191148 | October 9, 2018 | - | - | - | - | Download |
| N021153 | 1 | 6191148*PED | April 9, 2019 | - | - | - | - | Download |
| N021153 | 1 | 6369085 | May 25, 2018 | Y | Y | U - 729 | - | Download |
| N021153 | 1 | 6369085 | May 25, 2018 | Y | Y | U - 729 | - | Download |
| N021153 | 1 | 6369085*PED | November 25, 2018 | - | - | - | - | Download |
| N021153 | 1 | 6428810 | November 3, 2019 | - | Y | U - 469 | - | Download |
| N021153 | 1 | 6428810 | November 3, 2019 | - | Y | U - 469 | - | Download |
| N021153 | 1 | 6428810 | November 3, 2019 | - | Y | U - 469 | - | Download |
| N021153 | 1 | 6428810*PED | May 3, 2020 | - | - | - | - | Download |
| N021153 | 1 | 7411070 | May 25, 2018 | Y | - | - | - | Download |
| N021153 | 1 | 7411070*PED | November 25, 2018 | - | - | - | - | Download |
| N021153 | 1 | 8466175 | May 25, 2018 | - | - | U - 1417 | - | Download |
| N021153 | 1 | 8466175*PED | November 25, 2018 | - | - | - | - | Download |
| USP Apparatus | Speed (RPMs) | Medium | Volume (mL) | Recommended Sampling Times (minutes) | Date Updated |
|---|---|---|---|---|---|
| - | - | Refer to USP | - | - | August 27, 2015 |
| Label | Link |
|---|---|
| FDA label | Download |
| FDA chemistry review | Download |
| FDA Pharmacology Review(s) | Download |
| FDA Clinical Pharmacology Biopharmaceutics Review(s) | Download |
| FDA BE Recommendation | Download |
| European Public Assessment Report |
| Territory | Brand name / Generic company name | Link |
|---|---|---|
| EU | - | |
| UK | - | |
| US | AUROBINDO PHARMA LTD* | |
| US | DR REDDYS LABS LTD* | Download |
| US | HETERO LABS LTD III* | Download |
| US | IVAX SUB TEVA PHARMS* | Download |
| US | MYLAN PHARMS INC* | Download |
| US | NEXIUM | Download |
| US | PERRIGO R AND D* (Tentative Approval) | |
| US | TORRENT PHARMS LTD* |
| Esomeprazole is the S-isomer of omeprazole, which is a mixture of the S- and R- isomers. |
| www.accessdata.fda.gov, www.drugbank.ca, www.ema.europa.eu, www.medicines.org.uk, dailymed.nlm.nih.gov |
