| Active Ingredient | ROSUVASTATIN CALCIUM |
|---|
| 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 |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| CRESTOR | (NDA) 021366 | IPR | TABLET;ORAL | 5 MG, 10 MG, 20 MG, 40 MG | 40 MG | August 12, 2003 | _ | _ | 1 New molecular entity (NME) | S Standard review drug | Prescription | AB |
| Parameters | Details |
|---|---|
| Structural Formula |
 |
| Chemical Name | bis[(E)-7-[4-(4-fluorophenyl)-6-isopropyl-2[methyl(methylsulfonyl)amino] pyrimidin-5-yl](3R,5S)-3,5-dihydroxyhept-6-enoic acid] calcium salt |
| CAS No | 287714-41-4 |
| Molecular Formula | (C22H27FN3O6S)2Ca |
| Molecular Weight | 1001.14 |
| Appearance | White amorphous powder |
| Solubility | Sparingly soluble in methanol, and slightly soluble in ethanol |
| Water Solubility | Sparingly soluble in water |
| Polymorphism | - |
| pKa (Strongest Acidic) | 4 (Predicted) |
| pKa (Strongest Basic) | -2.8 (Predicted) |
| Log P | 0.13 at pH of 7.0 |
| Identification | - |
| Degradation | - |
| Hygroscopic | - |
| Photostability study | - |
| Melting Point | - |
| BCS Class | - |
| Manufacture of API | - |
| Parameters | Details |
|---|---|
| Indications and Usage | CRESTOR is an HMG Co-A reductase inhibitor indicated for: • patients with primary hyperlipidemia and mixed dyslipidemia as an adjunct to diet to reduce elevated total-C, LDL-C, ApoB, nonHDL-C, and TG levels and to increase HDL-C. • pediatric patients 8 to 17 years of age with heterozygous familial hypercholesterolemia (HeFH) to reduce elevated total-C, LDL-C and ApoB after failing an adequate trial of diet therapy. • patients with hypertriglyceridemia as an adjunct to diet • patients with primary dysbetalipoproteinemia (Type III hyperlipoproteinemia) as an adjunct to diet • patients with homozygous familial hypercholesterolemia (HoFH) to reduce LDL-C, total-C, and ApoB • slowing the progression of atherosclerosis as part of a treatment strategy to lower total-C and LDL-C as an adjunct to diet • risk reduction of MI, stroke, and arterial revascularization procedures in patients without clinically evident CHD, but with multiple risk factors Limitations of use: • CRESTOR has not been studied in Fredrickson Type I and V dyslipidemias. |
| Dosage and Administration |
• CRESTOR can be taken with or without food, at any time of day. • Dose range: 5-40 mg once daily. Use 40 mg dose only for patients not reaching LDL-C goal with 20 mg. • Adult HoFH: Starting dose 20 mg/day • Pediatric patients with HeFH: 5 to 10 mg/day for patients 8 to less than 10 years of age, and 5 to 20 mg/day for patients 10 to 17 years of age. • Pediatric patients with HoFH: 20 mg/day for patients 7 to 17 years of age |
| Mechanism of action | CRESTOR is a selective and competitive inhibitor of HMG-CoA reductase, the rate-limiting enzyme that converts 3-hydroxy-3-methylglutaryl coenzyme A to mevalonate, a precursor of cholesterol. In vivo studies in animals, and in vitro studies in cultured animal and human cells have shown rosuvastatin to have a high uptake into, and selectivity for, action in the liver, the target organ for cholesterol lowering. In in vivo and in vitro studies, rosuvastatin produces its lipid-modifying effects in two ways. First, it increases the number of hepatic LDL receptors on the cell-surface to enhance uptake and catabolism of LDL. Second, rosuvastatin inhibits hepatic synthesis of VLDL, which reduces the total number of VLDL and LDL particles. |
| Absorption | In clinical pharmacology studies in man, peak plasma concentrations of rosuvastatin were reached 3 to 5 hours following oral dosing. Both C max and AUC increased in approximate proportion to CRESTOR dose. The absolute bioavailability of rosuvastatin is approximately 20%. The AUC of rosuvastatin does not differ following evening or morning drug administration. |
| Food Effect | Administration of CRESTOR with food did not affect the AUC of rosuvastatin. |
| Distribution | Mean volume of distribution at steady-state of rosuvastatin is approximately 134 liters. Rosuvastatin is 88% bound to plasma proteins, mostly albumin. This binding is reversible and independent of plasma concentrations. |
| Metabolism | Rosuvastatin is not extensively metabolized; approximately 10% of a radiolabeled dose is recovered as metabolite. The major metabolite is N-desmethyl rosuvastatin, which is formed principally by cytochrome P450 \ 2C9, and in vitro studies have demonstrated that N-desmethyl rosuvastatin has approximately one-sixth to one-half the HMG-CoA reductase inhibitory activity of the parent compound. Overall, greater than 90% of active plasma HMG-CoA reductase inhibitory activity is accounted for by the parent compound. |
| Elimination | Following oral administration, rosuvastatin and its metabolites are primarily excreted in the feces (90%). The elimination half-life (t 1/2 ) of rosuvastatin is approximately 19 hours. After an intravenous dose, approximately 28% of total body clearance was via the renal route, and 72% by the hepatic route. |
| Peak plasma time (Tmax) | 3 to 5 hours |
| Half life | 19 hours |
| Bioavailability | 20% |
| Age, gender | There were no differences in plasma concentrations of rosuvastatin between men and women. There were no differences in plasma concentrations of rosuvastatin between the nonelderly and elderly populations (age ≥65 years). |
| DMF | Status | Type | Submit Date | Holder |
|---|---|---|---|---|
| 20592 | A | II | June 12, 2007 | GLENMARK PHARMACEUTICALS LTD |
| 20629 | A | II | June 22, 2007 | AUROBINDO PHARMA LTD |
| 20671 | A | II | July 12, 2007 | TEVA PHARMACEUTICAL INDUSTRIES LTD |
| 20677 | A | II | July 2, 2007 | ZHEJIANG NEO DANKONG PHARMACEUTICAL CO LTD |
| 20705 | A | II | July 18, 2007 | CHANGZHOU PHARMACEUTICAL FACTORY |
| 20712 | A | II | July 25, 2007 | MSN LABORATORIES PRIVATE LTD |
| 20751 | A | II | July 27, 2007 | ZHEJIANG NEO DANKONG PHARMACEUTICAL CO LTD |
| 20765 | A | II | August 9, 2007 | LEK PHARMACEUTICALS DD |
| 23223 | A | II | October 29, 2009 | CHANGZHOU PHARMACEUTICAL FACTORY |
| 23592 | A | II | February 26, 2010 | EGIS PHARMACEUTICALS PLC |
| 23599 | A | II | March 2, 2010 | MSN LABORATORIES LTD |
| 23766 | A | II | April 27, 2010 | MYLAN LABORATORIES LTD |
| 23975 | A | II | July 15, 2010 | MSN LABORATORIES PRIVATE LTD |
| 25050 | I | II | June 2, 2011 | PORTON FINE CHEMICALS LTD |
| 25117 | I | II | July 7, 2011 | PHARMACEUTICAL WORKS POLPHARMA SA |
| 25781 | A | II | February 10, 2012 | ZHEJIANG NEO DANKONG PHARMACEUTICAL CO LTD |
| 26073 | A | II | May 31, 2012 | CADILA HEALTHCARE LTD |
| 26150 | A | II | February 8, 2012 | APOTEX PHARMACHEM INC |
| 26540 | A | II | October 11, 2012 | BIOCON LTD |
| 26781 | A | II | April 9, 2013 | LUPIN LTD |
| 27633 | A | II | October 28, 2013 | HETERO DRUGS LTD |
| 27675 | A | II | October 8, 2013 | BIOCON LTD |
| 27769 | A | II | December 26, 2013 | ZHEJIANG HISUN PHARMACEUTICAL CO LTD |
| 27777 | A | II | September 6, 2013 | SHANGHAI DESANO CHEMICAL PHARMACEUTICAL CO LTD |
| 27813 | A | II | March 14, 2014 | JUBILANT GENERICS LTD |
| 27879 | A | II | February 7, 2014 | TEVA PHARMACEUTICAL INDUSTRIES LTD |
| 28022 | A | II | May 8, 2014 | LEK PHARMACEUTICALS DD |
| 28028 | A | II | March 18, 2014 | MACLEODS PHARMACEUTICALS LTD |
| 28334 | A | II | June 13, 2014 | DR REDDYS LABORATORIES LTD |
| 28659 | A | II | October 7, 2014 | AMOLI ORGANICS PVT LTD |
| 28888 | A | II | January 12, 2015 | GLENMARK PHARMACEUTICALS LTD |
| 29190 | A | II | December 3, 2015 | DELMAR CHEMICALS INC |
| 29397 | A | II | July 3, 2015 | HEC PHARM CO LTD |
| 30133 | A | II | December 13, 2015 | MELODY HEALTHCARE PVT LTD |
| Parameters | Details | ||||
|---|---|---|---|---|---|
| Strength | 10 MG | 40 MG | 20 MG | 5 MG | |
| Excipients used | Microcrystalline cellulose NF, lactose monohydrate NF(91.3 mg), tribasic calcium phosphate NF, crospovidone NF, magnesium stearate NF | Microcrystalline cellulose NF, lactose monohydrate NF(168.32 mg), tribasic calcium phosphate NF, crospovidone NF, magnesium stearate NF | Microcrystalline cellulose NF, lactose monohydrate NF(182.6 mg), tribasic calcium phosphate NF, crospovidone NF, magnesium stearate NF | Microcrystalline cellulose NF, lactose monohydrate NF ( 94.88 mg), tribasic calcium phosphate NF, crospovidone NF, magnesium stearate NF | |
| Composition of coating material | Hypromellose NF, triacetin NF, titanium dioxide USP, red ferric oxide NF |
Hypromellose NF, triacetin NF, titanium dioxide USP, yellow ferric oxide | |||
| Composition of caspule shell | - | ||||
| Pharmaceutical Development | - | ||||
| Manufacture of the product | - | ||||
| Tablet / Capsule Image |
|
|
|
|
|
| Appearance | US: Pink, round, biconvex, coated tablets. Debossed “CRESTOR” and “10” on one side EU: Round, pink coloured tablets, intagliated with 'ZD4522' and '10' on one side and plain on the reverse. | US: Pink, oval, biconvex, coated tablets. Debossed “CRESTOR” on one side and “40” on the other side EU: Oval, pink coloured tablets, intagliated with 'ZD4522' on one side and '40' on the reverse. | US: Pink, round, biconvex, coated tablets. Debossed “CRESTOR” and “20” on one side EU: Round, pink coloured tablets, intagliated with 'ZD4522' and '20' on one side and plain on the reverse. | US: Yellow, round, biconvex, coated tablets. debossed “CRESTOR” and “5” on one side EU: Round, yellow coloured tablets, intagliated with 'ZD4522' and '5' on one side and plain on the reverse | |
| Imprint code / Engraving / Debossment | US: Debossed “CRESTOR” and “10” on one side EU:intagliated with 'ZD4522' and '10' on one side and plain on the reverse | US: Debossed “CRESTOR” on one side and “40” on the other side EU: intagliated with 'ZD4522' on one side and '40' on the reverse | US: Debossed “CRESTOR” and “20” on one side EU: intagliated with 'ZD4522' and '20' on one side and plain on the reverse | US: Debossed “CRESTOR” and “5” on one side EU: intagliated with 'ZD4522' and '5' on one side and plain on the reverse | |
| Score | No score | No score | No score | No score | |
| Color | Pink | Pink | Pink | Yellow | |
| Shape | Round, biconvex | Oval | Round, biconvex | Round, biconvex | |
| Dimension | 7 mm | - | 9 mm | 7 mm | |
| Mfg by | AstraZeneca UK Ltd (EU/UK) | ||||
| Mfg for | - | ||||
| Marketed by | AstraZeneca UK Ltd (EU/UK) | ||||
| Distributed by | AstraZeneca Pharmaceuticals LP (US) | ||||
| Application No. | Prod No | Patent No | Patent Expiration | Drug Substance Claim | Drug Product Claim | Patent Use Code | Delist Requested | Link |
|---|---|---|---|---|---|---|---|---|
| N021366 | 2 | 6316460 | August 4, 2020 | - | Y | - | - | Download |
| N021366 | 2 | 6316460*PED | February 4, 2021 | - | - | - | - | Download |
| N021366 | 2 | 6858618 | December 17, 2021 | - | - | U - 1807 | - | Download |
| N021366 | 2 | 6858618 | December 17, 2021 | - | - | U - 1807 | - | Download |
| N021366 | 2 | 6858618 | December 17, 2021 | - | - | U - 1807 | - | Download |
| N021366 | 2 | 6858618*PED | June 17, 2022 | - | - | - | - | Download |
| N021366 | 2 | 7030152 | April 2, 2018 | - | - | U - 1032 | - | Download |
| N021366 | 2 | 7030152*PED | October 2, 2018 | - | - | - | - | Download |
| N021366 | 2 | 7964614 | April 2, 2018 | - | - | U - 1032 | - | Download |
| N021366 | 2 | 7964614*PED | October 2, 2018 | - | - | - | - | Download |
| N021366 | 2 | RE37314 | January 8, 2016 | Y | - | - | - | Download |
| N021366 | 2 | RE37314*PED | July 8, 2016 | - | - | - | - | Download |
| USP Apparatus | Speed (RPMs) | Medium | Volume (mL) | Recommended Sampling Times (minutes) | Date Updated |
|---|---|---|---|---|---|
| II (Paddle) | 50 | 0.05 M Sodium Citrate Buffer pH 6.6 ± 0.05 | 900 | 10, 20, 30 and 45 | November 10, 2010 |
| 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 | CRESTOR | Download |
| UK | CRESTOR | Download |
| US | ALKEM LABS LTD (ANDA # 206465)* (Tentative Approval) | |
| US | APOTEX CORP (ANDA # 079145)* (Prescription) | |
| US | AUROBINDO PHARMA (ANDA # 079170)* (Prescription) | |
| US | BIOCON LIMITED (ANDA # 207752)* (Tentative Approval) | |
| US | CRESTOR | Download |
| US | GLENMARK GENERICS (ANDA # 079172)* (Prescription)) | |
| US | MYLAN PHARMA (ANDA # 079161)* (Prescription) | |
| US | PAR PHARM (ANDA # 079168)* (Prescription) | |
| US | SANDOZ (ANDA # 079171)* (Prescription) | |
| US | SUN PHARMA GLOBAL (ANDA # 079169)* (Prescription) | |
| US | TEVA PHARMS (ANDA # 079166)* (Prescription) | |
| US | TORRENT PHARMS LLC (ANDA # 201619)* (Tentative Approval) | |
| US | WATSON LABS INC (ANDA # 079167)* (Prescription) | Download |
| NPP Exclusivity Expiration on: Nov 20, 2018. Date of first authorisation/renewal of the authorisation in EU on 21st March 2003/6th November 2012. |
| www.accessdata.fda.gov, www.drugbank.ca, www.ema.europa.eu, www.medicines.org.uk, dailymed.nlm.nih.gov |
