All in Japan: Statins Enterprise-wide Use License - All approved medicinal products in Japan STATINS Table of Contents 1. Introduction Key Findings 2. Type/generations of statins Table 1. Type/generations of statins 3. Statin products approved in Japan Table 2. Approval classification of the prescription medicinal products Table 3. Approval statistics of statin products in Japan Graph 1. Approval share by type of statins Graph 2. Approval share by approval class Table 4. Alphabetical list of statin products approved in Japan Table 5. Individual statin products approved in Japan Disclaimer and Publisher Information Note: The documents from the Japan Monitor "All in Japan" series provide concise up- to-date description of each product from a definite therapeutic category approved in Japan. Further details could be found in the web site of JKS, in the Key and Basic documents available in the JKS Document Store or by enquiring directly to JKS at regulatory@jouhoukoukai.com. 1. Introduction     The prototype of the product line, known now as statins, was discovered by Dr. Akira Endo in Sankyo's Tokyo laboratories in the early 1970s. The identification of mevastatin (ML-236B, compactin) resulted from nearly a century of biomedical research on the cholesterol biosynthesis, determining HMG-CoA reductase function in the conversion to a key metabolic precursor, mevalonate, provided the opportunity to therapeutically inhibit this enzyme.          The consequential intensive laboratory, preclinical and clinical development led to the first world-wide approval of this prototype statin drug in 1986. Generically known as pravastatin sodium (and more commonly referred to as just "pravastatin"), it was sold in US as Pravachol. In Japan pravastatin was registered by Sankyo as Mevalotin which became the first Japanese domestic "blockbuster" drug with sales over 1 billion US$ annually.          Further scientific endeavor and commercial competition has brought 8 chemical entities from the statin family to the international pharmaceutical market (Table 1). In Japan, five of these statin entities (pravastatin, simvastatin, fluvastatin, atorvastatin and pitavastatin) have gained approval, however in 2001 fluvastatin was withdrawn, while an application for Rosuvastatin was submitted in 2003 and lovastatin is yet to enter development in Japan.          In terms of efficacy, statin entities are unofficially classified as I, II and III generation, or alternatively as "standard" statins (I and II generation) and "strong" or superstatins (III generation). Pitavastatin aside, the general trend has been for the statin entity to be approved abroad before registered in Japan albeit in case of simvastatin the difference between FDA and MHLW approval timelines was on the scale of less than a year (Table 1).          In contrast to other therapeutic classes, the introduction and development of statin medicinal products in Japan have been both commercially highly successful and lacking the cultural controversies normally associated with the launch of foreign based entities in Japan. However, the incremental increase in Japan registered statins has been drastically affected by two milestone events. Firstly, following a series of rhabdomyolysis-related deaths worldwide, Bayer Yakuhin KK decided to voluntarily withdraw in 2001 Baycol thus lowering the number of approved statins in Japan to just three. Secondly the expiration of the patent rights for both pravastatin and simvastatin, resulted in a flurry of generics approved en masse in July 2003. As detailed in Table 3 and Graph 1 and Graph 2, at present, the "standard" statins (or I generation) group is completely dominated by generic versions namely 27 generic products of pravastatin and 17 of simvastatin.          Regarding market prospects, some preliminary figures indicate that market share of "standard" statins will further erode due to both advance of the superstatins - including tentatively rosuvastatin, and ceding to generics competitors. In May 2004, Sankyo KK released the Mevalotin revenues for the fiscal 2002, 2003 and 2004 (estimation) as follows: 110.7, 98.3 and 82.3 billion Yen and in efforts to bolster further sales attrition, have launched a marketing strategy targeting the pleiotropic effects of the drug .          The overall outlook of the Japanese statin market is positive as New Chemical Entity statins innovated from Japan pharma will continue to buoy the dyslipidemia market, with a 55% stake of all Japan registered statins; pravastatin continues to be the mainstay. Since expiry of the Mevalotin(r) patent in July 2003, competitiveness of the Japan statin market normally enticed by blockbuster New Chemical Entities has become swamped by "standard" statin generics, totaling a 86% share from both pravastatin and simvastatin Japan registered statins alone. The Japanese superstatin market is still in its infancy with only a mere representation of less than 6% of the total Japan registered statins volume. The combined volume of standard and superstatins is projected to exceed 2, 500 billion Yen in 2004 and near 4,000 billion Yen in 2008 . Key Findings * Apart from globally withdrawn cerivastatin, out of all 7 known New Chemical Entities of statins registered world-wide, 5 are already approved in Japan and Rosuvastatin is expecting approval. * Post July 2003 expiry of the Mevalotin(r) patent saw the MHLW approved 44 generics comprising of pravastatin (27) and simvastatin (17) formulations, making up 86% of the total Japan registered statins volume. * Pravastatin still dominates the statin prescription registry with 55% of the total Japan registered statins volume, followed by simvastatin at 35%; the superstatin class with pitavastatin and atorvastatin accounts for barely under 6%. * Currently only Mevalotin(r) and Mevatorte are the two Japan registered statins prescribed as a granule formulation in Japan. * Time lag between international and Japanese approvals has been 10 years, 3 years, 2 years, 2 years and 0 years for fluvastatin, pravastatin, atorvastatin, cerivastatin (withdrawn worldwide) and simvastatin respectively. 2. Type/generations of statins Table 1. Type/generations of statins Statin International status Approval in Japan Generic Gene- ration Brand First approval Maker / Marketing Approval Brand Maker / Marketing pravastatin I Pravachol 1986 BMS 1989 Mevalotin (+ 27 generics) Sankyo KK lovastatin I Mevacor 1987 Merck Not entered simvastatin I Zocor 1991 Merck 1991 Lipovas (+ 17 generics) Banyu/Merck fluvastatin II Lescol 1993 Novartis 2003 Lochol Novartis Pharma KK cerivastatin III Baycol 1997 Bayer 1999 Baycol Bayer Yakuhin KK atorvastatin III Lipitor 1998 Pfizer 2000 Lipitor Pfizer KK rosuvastatin III Crestor 2003 AstraZeneca Submitted in 2003 pitavastatin III Livalo 2003 Kowa KK / Sankyo KK 2003 Livalo Kowa KK / Sankyo KK 3. Statin products approved in Japan    All formulations of the statin products registered in Japan by June 2004 are listed in Table 5 below. Included are a comprehensive profile of each product's approval and market entry timeline, as well as relevant medical, regulatory, formulation and therapeutic remarks on the product. The formulations are grouped by brand and the year of approval, arranged alphabetically. Table 2. Approval classification of the prescription medicinal products in Japan Class Description 1 Medicines with new active ingredients 2 New combination medicines excluding medicines Class 7-2 and trivial combinations 3 Medicines with new route of administration 4 Medicines with new indications 5 Medicines with new dosage forms 6 Medicines with new doses 7 Medicines with additional dosage forms: excluding the medicines Class 5 7-2 Medicines with similar formulations 8 Miscellaneous Table 3. Approval statistics of statin products in Japan Generic Name / Drug Candidate Approved in Japan - n (% of total Statins) Approval Classification - Number in each approval class (% of total Statins) Class 1 Class 7 Class 7-2 Class 8 Additional Formulation - n (Other than Tablet e.g. granules) Approval in July 2003 - n (% of total Statins; Class One Approval Date) Atorvastatin Calcium Hydrate 1(1.96) 1(1.96) - - - - - - (May 2000) Fluvastatin Sodium 2(3.92) 1(1.96) - - 1(1.96) - - (June 2003) Pitavastatin Calcium 2(3.92) 1(1.96) - - 1(1.96) - - (Sept. 2003) Pravastatin Sodium 28(54.9) 1(1.96) 1(1.96) 20(39.2) 6(11.8) 2 (granules) 27 (52.9; Sept 2001) Simvastatin 18(35.3) 1(1.96) - 12(23.5) 5(9.80) - 17 (33.3; Nov. 1991) Total 51(100) 5(9.80) 1(1.96) 32(64.7) 13(23.5) 44 (86.2) Graph 1. Approval share by type of statins Graph 2. Approval share by approval class Table 4. Alphabetical list of statin products approved in Japan 1. Alsetin 2. Amel Pravastatin Na 3. Amel Simvastatin 4. Cholerit 5. KN Pravastatin Na 6. KN Pravastatin Na 7. Liduc M 8. Lipitor 9. Lipoblock 10. Lipodown 11. Lipodown 12. Lipokoban 13. Lipo-off 14. Lipovas 15. Lipovatol 16. Lipozart 17. Livalo 18. Livalo 19. Lochol 20. Lochol 21. Maibastan 22. Meek Simvastatin 23. Meek Simvastatin 24. Mevalation 25. Mevalation 26. Mevalect 27. Mevalect 28. Mevalect 29. Mevalocut 30. Mevalotin (Tablet & Granules) 31. Mevan 32. Mevarich 33. Mevarich 34. Mevasrolin 35. Mevastan 36. Mevatorte (Tablet & Granules) 37. Mindorotin 38. Ohara Simvastatin 39. Ohara Simvastatin 40. Ohara Simvastatin 41. Pravalon 42. Pravamate 43. Pravastan 44. Pravastan 45. Pravastatin Sodium 46. Pravatin 47. Ramian 48. Simvamerck 49. Sinstatin 50. Sinstatin 51. Tatsuplamin Table 5. Individual statin products approved in Japan 1. ALSETIN Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination ALSETIN Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00302000 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG-CoA Reductase Inhibitor - Dyslipidemia Medicine Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (1st revision, new format) Prescription Medicine July 2003 July 2003 Product information continues on the next page 1. ALSETIN Tablets Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Pravastatin sodium 5mg; 10mg Additives: magnesium stearate; trace additives: hydroxycellulose, D- mannitol, ferric oxide Chemical Formula: C23H35NaO7 Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate Alsetin 5mg, Tablets of 100 1,200 1,400 (PTP (Press through packing)); 500 (Bottled packaging) Alsetin 10mg, Tablets of 100, 600, 700, 1,200 (PTP packaging) 500 (Bottled packaging) 5mg: Diameter - 6.5mm; Weight - 90 mg; Thickness - 2.2mm Comments: White tablet; 10mg: Diameter - 7.5mm; Weight - 140mg; Thickness - 2.5mm; Comments: White with minute red line dividing half the tablet 5mg 10mg Manufacturer & Marketing Agent: Pacific Pharmaceutical Industries K.K. 16-29 Marunouchi 2 Chome, Chuo-ku, Nagoya 2. AMEL PRAVASTATIN Na 5mg/10mg Tablets Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination AMEL PRAVASTATIN Na Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 (15AM)358 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (2nd Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 2. AMEL PRAVASTATIN Na 5mg/10mg Tablets Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Effective ingredient in 1 tablet: 5mg/10mg of pravastatin sodium Additives: Anhydrous lactose, microcystalline hydroxypropylcellulose, maize starch, talc, hydroxypropylcellulose, calcium stearate C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate 5mg of Pravastatin Na: 100, 700, 1,000 tablets (PTP & bottled packing) 10mg of Pravastatin Na: 100, 700, 1,000 tablets (PTP)), 500 (bottled) Tablet Form: Round with half line on one side, pink/red. Size: 7.5mm, 2.5mm, 140mg weight Manufacturer & Marketing Agent: Kyowa Yakuhin K.K., 5-13-9, Nishi- Nakashima, Yodogawa-ku, Osaka- City 3. AMEL SIMVASTATIN Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination AMEL SIMVASTATIN Simvastatin 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 (15AM)355 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG CoA Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (2nd Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 3. AMEL SIMVASTATIN Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent One tablet, contains 5 mg of simvastatin; Excipients: lactose, microcrystalline cellulose, hydroxypropylcellulose, citric acid, magnesium stearate magnesium, anhydrous silicic acid, butylhydroxyanisol Chemical Formula: C25H38O5; Chemical Name: (+)-(1S,3R,7S,8S,8aR)- 1,2,3,7,8,8a-Hexahydro-3,7-dimethyl-8-[2- [(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2- yl]ethyl]-1-naphtyl-2,2-dimethylbutanoate; 100 tablets (PTP), 500 tablets (foil ), 700 tablets (PTP), 1,000 tablets (PTP) White with one side as a two division line; Size: diameter 6.5mm; thickness 2.4mm; weight 100mg Manufacturer & Marketing Agent: Kyowa Pharmaceutical Co. Ltd. 5-13-9, Nishi- Nakashima, Yodogawa-ku, Osaka 4. CHOLERIT Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination CHOLERIT Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00337 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG CoA Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan January 2002 (5th Revision) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 4. CHOLERIT Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Cholerit 10mg contains 10 mg of pravastatin sodium per tablet. Also contains lactose, maize starch, hydroxypropylcellulose, magnesium stearate, ferric oxide as additives Chemical Formula: C23H35NaO7; Chemical Name: sodium(+)-(3R,5R)-3,5- Dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate; Cholerit 5 mg: 100 tablets (10 tablet 10), 500 tablets (10 tablet 50) (PTP) Cholerit 10 mg: 100 tablets (10 tablet 10), 500 tablets (10 tablet 50) (PTP) Cholerit 10 mg are red tablets marked with a line on one side. Diameter 8.0 mm; thickness 2.4 mm Manufacturer & Marketing Agent: Fusou Yakuhin Kogyo K.K. 7-10,1-chome,Syudo- Cho, Osaka 5. KN PRAVASTATIN Na 5/10 Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination KN PRAVASTATIN Na Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 (15AM)299 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (2nd Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 5. KN PRAVASTATIN Na 5/10 Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Effective ingredient in 1 tablet: 5mg/10mg of pravastatin sodium Additives: D-mannitol, crystalline cellulose, modified starch, magnesium stearate Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate KN Pravastatin Na Tablets 5mg: 100, 700, 1,000 tablets (PTP) & 1000 (bottled) KN Pravastatin Na Tablets 10mg: 100, 700, 1,000 tablets (PTP), 500 (bottled) Round white tablet; Size: 6.6mm, 2.2mm, 90mg weight Manufacturer & Marketing Agent: Kobayashi Chemical K.K. 26-17, 2-Chome, Ichihime, Kanadu- Cho, Sakai-gun, Fukui 6. KN PRAVASTATIN Na 5/10 Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination KN PRAVASTATIN Na Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 (15AM)299 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (2nd Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 6. KN PRAVASTATIN Na 5/10 Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Effective ingredient in 1 tablet: 5mg/10mg of pravastatin sodium Additives: D-mannitol, crystalline cellulose, modified starch, magnesium stearate Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate KN Pravastatin Na Tablets 5mg: 100, 700, 1,000 tablets (PTP) & 1000 (bottled) KN Pravastatin Na Tablets 10mg: 100, 700, 1,000 tablets (PTP)), 500 (bottled) Round white tablet: 6.6mm, 2.2mm, 90mg weight Manufacturer & Marketing Agent: Kobayashi Chemical K.K. 26-17, 2-Chome, Ichihime, Kanadu- Cho, Sakai-gun, Fukui 7. LIDUC M 10 Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination LIDUC M (r) Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00255000 Class 7-2 Hyperlipidemia Familial Hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (2nd Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 7. LIDUC M 10 Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Liduc M 10mg tablet contains: pravastatin sodium 10mg. Additives: anhydrous citric acid powder, ferric oxide, dimethylpolysiloxane (clinical grade), refined stevia extract, maize starch, fractionated polyvinylalcohol, D- mannitol and l-menthol Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate Liduc M 10mg: 100 and 1000 tablets (PTP) Liduc M 10mg: Pink tablet a side line, Diameter 9.5mm, Thickness 3.9mm, Weight 280mg Manufacturer: San Nova K.K. 3038-2, Serada, Ojima-machi, Nitta-gun, Gunma Marketing Agent: Elmed Ezai K.K. 3-23- 5, Higashi-Ikebukuro, Toshima-ku, Tokyo 8. LIPITOR 5mg/10mg Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination LIPITOR(r) Atorvastatin Calcium Hydrate 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category May 2000 21200AMZ00158 Class 1 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan August 2003 (10th Edition) Prescription Medicine May 2000 May 2000 Product Information continues on the next page 8. LIPITOR 5mg/10mg Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Lipitor 5mg tablet contains: atorvastatin calcium hydrate 5.42mg (5.0mg as atorvastatin), lactose, crystal cellulose, sublimed calcium carbonate, croscarmellose sodium, polysolvent 80, hydroxypropylcellulose, magnesium stearate, hydroxypropylmethylcellu lose, macrogol, titanium oxide, talc, ferric oxide; Lipitor 10mg tablet contains: atorvastatin calcium hydrate 10.84mg (10.0mg as atorvastatin), lactose, crystal cellulose, sublimed calcium carbonate, croscarmellose sodium, polysolvent 80, hydroxypropylcellulose, magnesium stearate, hydroxypropylmethylcellu lose, macrogol, titanium oxide, talc Chemical Formula: C66H68CaF2N4O10・3H2O; Chemical Name: (-)-Monocalcium bis {[3R,5R)- 7-[2-(4-fluorophenyl)-5-isopropyl-3-phenyl-4- phenylcarbamoyl-1H-pyrrol-1-yl]-3,5- dihydroxyheptanoate}trihydrate Lipitor 5mg (PTP): 100 tablets、140 (14 tablets x 10), 500 tablets. Lipitor 10.0mg (PTP): 100 tablets, 140 (14 tablets 10), 500 tablets、 700 (14 tablets 50), 1000 tablets Lipitor 10.0mg (Bottled): 500 tablets Lipitor 5mg: Very thin pink film coated tablet, Diameter 5.6mm, Thickness 2.7mm, Weight 72mg Lipitor 10mg: White tablet, Diameter 6.1mm, Thickness 2.7mm, Weight 88mg Manufacturer: Yamanouchi Seiyaku K.K. 2-3-11, Nihonbashi-honcho, Chuo-ku, Tokyo Marketing Agent: Pfizer K.K. 3-22-7, Yoyogi, Shibuya-ku, Tokyo 9. LIPOBLOCK 5 Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination LIPOBLOCK Simvastatin 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00278000 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor - Dyslipidemia Medicine Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (2nd Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 9. LIPOBLOCK 5 Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Lipoblock 5 tablet contains: simvastatin 5.0mg. Additives: lactose, cellulose, hydroxypropylcellulose, butylhydroxyanisol, citric acid, magnesium stearate Chemical Formula: C25H38O5; Chemical Name: (+)-(1S,3R,7S,8S,8aR)- 1,2,3,7,8,8a-Hexahydro-3,7-dimethyl-8-[2- [(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2- yl]ethyl]-1-naphthyl 2,2-dimethylbutanoate Lipoblock 5: PTP: 100,140, 700 and 1000 tablets Bottled: 500 tablets Lipoblock 5: White with one side line, Diameter 6.35mm, Thickness 2.4mm, Weight 100mg Manufacturer & Marketing Agent: Towa Yakuhin K.K. 2- 11, Shinbashi-cho, Kadoma-city, Osaka 10. LIPODOWN 5 Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination LIPODOWN Simvastatin 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00374000 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor - Dyslipidemia Medicine Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan October 2003 (3rd Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 10. LIPODOWN 5 Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Lipodown 5 tablet contains: simvastatin 5.0mg. Additives: citric acid, anhydrous silicilic acid, magnesium stearate, maize starch, lactose, hydroxyprpylcellulose, butyhydroxyanisol Chemical Formula: C25H38O5; Chemical Name: (+)-(1S,3R,7S,8S,8aR)- 1,2,3,7,8,8a-Hexahydro-3,7-dimethyl-8-[2- [(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2- yl]ethyl]-1-naphthyl 2,2-dimethylbutanoate Lipodown 5: PTP: 100 (10 tablets 10), 500 (10 tablets 50), 700 (14 tablets 50) Lipodown 5: White odorless tablet with one side line, Diameter 6.5mm, Thickness 2.4mm, Weight 100mg Manufacturer: Medisa Shinyaku K.K. 15-9, 4-Chome, Nihonbashi-honcho, Chuo-ku, Tokyo Marketing Agent: Asahi Kasei Pharma K.K. 9-1, Kanda- mitoshiro-cho, Chiyoda-ku, Tokyo 11. LIPODOWN 5 Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination LIPODOWN Simvastatin 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00374000 Class 8 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor - Dyslipidemia Medicine Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan October 2003 (3rd Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 11. LIPODOWN 5 Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Lipodown 5 tablet contains: simvastatin 5.0mg. Additives: citric acid, anhydrous silicilic acid, magnesium stearate, maize starch, lactose, hydroxyprpylcellulose, butyhydroxyanisol Chemical Formula: C25H38O5; Chemical Name: (+)-(1S,3R,7S,8S,8aR)- 1,2,3,7,8,8a-Hexahydro-3,7-dimethyl-8-[2- [(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2- yl]ethyl]-1-naphthyl 2,2-dimethylbutanoate Lipodown 5: PTP: 100 (10 tablets 10), 700 (14 tablets 50), 1000 (10 tablets x 100) Lipodown 5: White with one side line, Diameter 6.5mm, Thickness 2.4mm, Weight 100mg Manufacturer: Medisa Shinyaku K.K. 15-9, 4-Chome, Nihonbashi-honcho, Chuo-ku, Tokyo Marketing Agent: Sawai Seiyaku K.K. 4- 25, 1-chome, Akagawa, Asahi-ku, Osaka-city 12. LIPOKOBAN Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination LIPOKOBAN Simvastatin 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00408000 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor - Dyslipidemia Medicine Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan June 2003 (2nd Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 12. LIPOKOBAN Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Lipokoban 5 tablet contains: simvastatin 5.0mg. Additives: Lactose, maize starch, microcrystalline cellulose, citric acid, crospovidone, hydroxypropylcellulose, magnesium stearate Chemical Formula: C25H38O5; Chemical Name: (+)-(1S,3R,7S,8S,8aR)- 1,2,3,7,8,8a-Hexahydro-3,7-dimethyl-8-[2- [(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran- 2-yl]ethyl]-1-naphthyl 2,2-dimethylbutanoate Lipokoban tablet: 100 tablets(10 tablets 10; PTP) 500 tablets (10 tablets 50; PTP) 500 tablets(bottled) 700 tablets (14 tablets 50; PTP) Lipokoban tablet: White with one side line, Diameter 6.5mm, Thickness 2.3mm, Weight 100mg Manufacturer: Kobayashi Yakugaku Kogyo K.K. 4-2, 3- chome, Shimo- meguro, Meguro-ku, Tokyo Marketing Agent: Noppon Iyakuhin Kogyo K.K. 6-21, 1- chome, Sougawa, Toyama-city, Toyama 13. LIPO-OFF 5 Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination LIPO-OFF Simvastatin 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00407000 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor - Dyslipidemia Medicine Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan June 2003 (2nd Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 13. LIPO-OFF 5 Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Lipo-off 5 tablet contains: simvastatin 5.0mg. Additives: Lactose, maize starch, microcrystalline cellulose, citric acid, crospovidone, hydroxypropylcellulose, magnesium stearate Chemical Formula: C25H38O5; Chemical Name: (+)-(1S,3R,7S,8S,8aR)- 1,2,3,7,8,8a-Hexahydro-3,7-dimethyl-8-[2- [(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2- yl]ethyl]-1-naphthyl 2,2-dimethylbutanoate Lipo-off 5: 100 (10 tablets 10; PTP) 500 (10 tablets 50; PTP) 500 tablets (bottled) 700 (14 tablets 50; PTP) Lipo-off 5: White with one side line, Diameter 6.5mm, Thickness 2.3mm, Weight 100mg Manufacturer & Marketing Agent: Nippon Iyakuhin Ko- gyo K.K. 6-21, 1- chome, Sougawa, Toyama-city, Toyama 14. LIPOVAS 5/10/20 Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination LIPOVAS(r) Simvastatin 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category November 1991 20300AMZ00735000 Lipovas 5 June 2002 21300AMZ00847000 Lipovas 10, 20 Class 1 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor - Dyslipidemia Medicine Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan February 2004 (12th Edition) Prescription Medicine November 1991 Lipovas 5 June 2002 Lipovas 10, 20 December 1991 Lipovas 5 June 2002 Lipovas 10, 20 Product Information continues on the next page 14. LIPOVAS 5/10/20 Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Lipovas 5, 10 & 20 tablets contain: simvastatin 5.0mg, 10.0mg & 20.0mg respectively; Additives: Lactose, cellulose, processed starch, hydrolyzed gelatin, crospovidone, citric acid, BHA, magnesium stearate Chemical Formula: C25H38O5; Chemical Name:(+)-(1S,3R,7S,8S,8aR)- 1,2,3,7,8,8a-Hexahydro-3,7-dimethyl-8-[2- [(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2- yl]ethyl]-1-naphthyl 2,2-dimethylbutanoate Lipovas 5: 100 (10 tablets 10), 500 (10 tablets 50), 700 (14 tablets 50), 1,000 (10 tablets 100) (PTP); 500 tablets (Bottled) Lipovas 10: 100 (10 tablets 10), 500 (10 tablets 50), 700 (14 tablets 50), 1,000 (10 tablets 100) PTP Lipovas 20: 28 (14 tablets 2), 100 (10 tablets 10), 500 (10 tablets 50), 700 (14 tablets 50) PTP Lipovas 5: White with one side line, Diameter 6.4mm, Thickness 2.4mm: Lipovas 10: White with one side line, Diameter 8.0mm, Thickness 3.0mm: Lipovas 20: White with one side line, Length 14.0mm, Width 7.5mm, Thickness 4.6mm: Manufacturer & Marketing Agent: Banyu Yakuhin K.K. 2- 2-3, Nihonbashi- honcho, Chu-o-ku, Tokyo 15. LIPOVATOL 5 Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination LIPOVATOL Simvastatin 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00278000 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor - Dyslipidemia Medicine Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (2nd Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 15. LIPOVATOL 5 Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Lipovatol 5 tablet contains: simvastatin 5.0mg. Additives: sucrose, alpha-starch, cellulose, crospovidone, citric acid, hydroxypropylcellulose, anhydrous silicilic acid, BHA, magnesium stearate Chemical Formula: C25H38O5; Chemical Name: (+)-(1S,3R,7S,8S,8aR)- 1,2,3,7,8,8a-Hexahydro-3,7-dimethyl-8-[2- [(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2- yl]ethyl]-1-naphthyl 2,2-dimethylbutanoate Lipovatol 5: PTP: 100, 500 and 1000 tablets Bottled: 500 tablets Lipodown 5: White with one side line, Diameter 6.5mm, Thickness 2.35mm, Weight 100mg Manufacturer & Marketing Agent: Toyo Pharma K.K. 287-1, Shimocho, Moroe-machi, Kanazawa 16. LIPOZART 5 Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination LIPOZART Simvastatin 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00416000 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor - Dyslipidemia Medicine Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (Newly Revised 1st Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 16. LIPOZART 5 Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Lipozart 5 tablet contains: simvastatin 5.0mg; Additives: Carmellose calcium, microcrystalline cellulose, magnesium stearate, lactose, hydroxypropylcellulose, butylhydroxyanisol Chemical Formula: C25H38O5; Chemical Name: (+)-(1S,3R,7S,8S,8aR)- 1,2,3,7,8,8a-Hexahydro-3,7-dimethyl-8-[2- [(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran- 2-yl]ethyl]-1-naphthyl 2,2-dimethylbutanoate Lipozart 5: 100, 600, 700, and 1,200 tablets (PTP), 500 (bottled) Lipozart 5: White with one side line, Diameter 6.5mm, Thickness 2.3mm, Weight 100mg Manufacturer & Marketing Agent: Yaiyo Yakuhin Kogyo K.K. 16-29 2-Chome, Marunouchi, Naka-ku, Nagoya-city 17. LIVALO 1mg/2mg Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination LIVALO(r) Pitavastatin Calcium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category September 2003 21500AMZ00459 Class 1 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan September 2003 (2nd Edition) Prescription Medicine September 2003 September 2003 Product Information continues on the next page 17. LIVALO 1mg/2mg Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Livalo 1mg tablet contains: pitavastatin calcium 1mg. Additives: lactose, hydroxypropylcellulose, hydroxypropylmethylcellu lose, magnesium alumina meta-citrate, magnesium stearate, triethyl citrate, silicon dioxide, titanium oxide, Carnauba Wax Livalo 2mg tablet contains: pitavastatin calcium 1mg. Additives: lactose, hydroxypropylcellulose, hydroxypropylmethylcellu lose, magnesium alumina meta-citrate, magnesium stearate, triethyl citrate, silicon dioxide, titanium oxide, Carnauba Wax Chemical Formula: C50H46CaF2N2O8; Chemical Name: (+)-Monocalcium bis{(3R,5S,6E)- 7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]- 3,5-dihydroxy-6-heptenoate} Livalo 1mg (PTP Packaging):100 tablets, 140(14 tablets 10), 500 tablets Livalo 2mg (PTP Packaging):100 tablets, 140(14 tablets 10), 500 tablets、700(14 tablets 50), 1000 tablets Livalo 2mg (Bottled): 500 tablets Livalo 1mg: White film coated tablet, Diameter 6.2mm, Thickness 2.6mm, Weight 85mg Livalo 2mg: White film coated tablet, Diameter 7.2mm, Thickness 3.0mm, Weight 127mg Manufacturer: Kowa K.K. 6-29, 3- Chome, Nishiki, Naka- ku, Nagoya-shi Marketing Agent: Sankyo K.K. 3-5-1 Nihonbashi-Honcho, Chuo-ku, Tokyo 18. LIVALO 1mg/2mg Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination LIVALO(r) Pitavastatin Calcium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category September 2003 21500AMZ00459 Class 8 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan September 2003 (2nd Edition) Prescription Medicine September 2003 September 2003 Product Information continues on the next page 18. LIVALO 1mg/2mg Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Livalo 1mg tablet contains: pitavastatin calcium 1mg; Additives: lactose, hydroxypropylcellulose, hydroxypropylmethylcellu lose, magnesium alumina meta-citrate, magnesium stearate, triethyl citrate, silicon dioxide, titanium oxide, Carnauba Wax Livalo 2mg tablet contains: pitavastatin calcium 2mg. Additives: lactose, hydroxypropylcellulose, hydroxypropylmethylcellu lose, magnesium alumina meta-citrate, magnesium stearate, triethyl citrate, silicon dioxide, titanium oxide, Carnauba Wax Chemical Formula: C50H46CaF2N2O8; Chemical Name: (+)-Monocalcium bis{(3R,5S,6E)- 7-[2-cyclopropyl-4-(4-fluorophenyl)-3-quinolyl]- 3,5-dihydroxy-6-heptenoate} Livalo 1mg (PTP): 100 tablets、140 (14 tablets 10), 500 tablets Livalo 2mg (PTP): 100 tablets、140 (14 tablets 10), 500 tablets、700 (14 tablets 50), 1000 tablets Livalo 2mg (Bottled): 500 tablets Livalo 1mg: White film coated tablet, Diameter 6.2mm, Thickness 2.6mm, Weight 85mg Livalo 2mg: White film coated tablet, Diameter 7.2mm, Thickness 3.0mm, Weight 127mg Manufacturer & Marketing Agent: Kowa K.K. 6-29, 3- Chome, Nishiki, Naka- ku, Nagoya-shi 19. LOCHOL 10mg/20mg/30mg Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination LOCHOL Fluvastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category June 2003 21500AMZ00035000 LOCHOL 10mg June 2003 21500AMZ00036000 LOCHOL 20mg June 2003 21500AMZ00037000 LOCHOL 30mg Class 1 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan June 2003 (2nd Edition) Prescription Medicine June 2003 June 2003 Product Information continues on the next page 19. LOCHOL 10mg/20mg/30mg Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Lochol 10mg, 20mg & 30mg tablet contains: fluvastatin sodium 10.53mg, 21.06mg & 31.59mg (as 10.0mg, 20.0mg & 30.0mg fluvastatin) respectively. Additives: sodium hydrogen carbonate, calcium carbonate, cellulose, carmellose calcium, talc, magnesium stearate, hydroxypropylmethylcellu lose, macrogol, titanium oxide, ferric oxide Chemical Formula: C24H25FNNaO4; Chemical Name: ()-(3RS,5SR,6E)-Sodium-7-[3- (4-fluorophenyl)-1-(1-methylethyl)-1H-indol-2- yl]-3,5-dihydroxy-6-heptenoate Lochol 10mg: PTP: 100 (10 tablets 10), 500 (10 tablets 50) Lochol 20mg: PTP: 100 (10 tablets 10), 500 (10 tablets 50), 700 (14 tablets 50), 1,000 (10 tablets 100) Plastic bottle: 500 tablets Lochol 30mg: PTP: 100 (10 tablets 10), 500 (10 tablets 50) Manufacturer: Nippon Ciba Geigy K.K. 4-17-30, Nishi- Azabu, Minato-ku, Tokyo Marketing Agent: Tanabe Seiyaku K.K. 2-10, 3-chome, Dosyo- machi, Chuo-ku, Saka- city Product Information continues on the next page 19. LOCHOL 10mg/20mg/30mg Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Lochol 10mg, 20mg & 30mg tablet contains: fluvastatin sodium 10.53mg, 21.06mg & 31.59mg (as 10.0mg, 20.0mg & 30.0mg fluvastatin) respectively. Additives: sodium hydrogen carbonate, calcium carbonate, cellulose, carmellose calcium, talc, magnesium stearate, hydroxypropylmethylcellu lose, macrogol, titanium oxide, ferric oxide Chemical Formula: C24H25FNNaO4; Chemical Name: ()-(3RS,5SR,6E)-Sodium-7-[3- (4-fluorophenyl)-1-(1-methylethyl)-1H-indol-2- yl]-3,5-dihydroxy-6-heptenoate Lochol 10mg: Buff filmed coated tablet, Diameter 5.7mm, Thickness 2.4mm, Weight 66mg Lochol 20mg tablet: Buff filmed coated tablet, Diameter 6.7mm, Thickness 3.4mm, Weight 129mg Lochol 30mg tablet: Buff filmed coated tablet, Diameter 7.7mm, Thickness 3.8mm, Weight 192mg Manufacturer: Nippon Ciba Geigy K.K. 4-17-30, Nishi- Azabu, Minato-ku, Tokyo Marketing Agent: Tanabe Seiyaku K.K. 2-10, 3-chome, Dosyo- machi, Chuo-ku, Saka- city 20. LOCHOL 10mg/20mg/30mg Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination LOCHOL Fluvastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category June 2003 21500AMZ00035000 LOCHOL 10mg June 2003 21500AMZ00036000 LOCHOL 20mg June 2003 21500AMZ00037000 LOCHOL 30mg Class 8 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan June 2003 (2nd Edition) Prescription Medicine June 2003 June 2003 Product Information continues on the next page 20. LOCHOL 10mg/20mg/30mg Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Lochol 10mg, 20mg & 30mg tablet contains: fluvastatin sodium 10.53mg, 21.06mg & 31.59mg (as 10.0mg, 20.0mg & 30.0mg fluvastatin) respectively. Additives: sodium hydrogen carbonate, calcium carbonate, cellulose, carmellose calcium, talc, magnesium stearate, hydroxypropylmethylcellu lose, macrogol, titanium oxide, ferric oxide Chemical Formula: C24H25FNNaO4; Chemical Name: ()-(3RS,5SR,6E)-Sodium-7-[3- (4-fluorophenyl)-1-(1-methylethyl)-1H-indol-2- yl]-3,5-dihydroxy-6-heptenoate Lochol 10mg: PTP: 100 (10 tablets 10), 500 (10 tablets 50) Lochol 20mg: PTP: 100 (10 tablets 10), 500 (10 tablets 50), 700 (14 tablets 50), 1,000 (10 tablets 100) Individual & bottled: 500 tablets Lochol 30mg: PTP: 100 (10 tablets 10), 500 (10 tablets 50) Manufacturer: Nippon Ciba Geigy K.K. 4-17-30, Nishi- Azabu, Minato-ku, Tokyo Marketing Agent: Novartis Pharma K.K. 4-17-30, Nishi-azabu, Minato-ku, Tokyo Product Information continues on the next page 20. LOCHOL 10mg/20mg/30mg Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Lochol 10mg, 20mg & 30mg tablet contains: fluvastatin sodium 10.53mg, 21.06mg & 31.59mg (as 10.0mg, 20.0mg & 30.0mg fluvastatin) respectively. Additives: sodium hydrogen carbonate, calcium carbonate, cellulose, carmellose calcium, talc, magnesium stearate, hydroxypropylmethylcellu lose, macrogol, titanium oxide, ferric oxide Chemical Formula: C24H25FNNaO4; Chemical Name: ()-(3RS,5SR,6E)-Sodium-7-[3- (4-fluorophenyl)-1-(1-methylethyl)-1H-indol-2- yl]-3,5-dihydroxy-6-heptenoate Lochol 10mg: Buff filmed coated tablet, Diameter 5.7mm, Thickness 2.4mm, Weight 66mg Lochol 20mg: Buff filmed coated tablet, Diameter 6.7mm, Thickness 3.4mm, Weight 129mg Lochol 30mg: Buff filmed coated tablet, Diameter 7.7mm, Thickness 3.8mm, Weight 192mg Manufacturer: Nippon Ciba Geigy K.K. 4-17-30, Nishi- Azabu, Minato-ku, Tokyo Marketing Agent: Novartis Pharma K.K. 4-17-30, Nishi-azabu, Minato-ku, Tokyo 21. MAIBASTAN 5mg Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination MAIBASTAN Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00363 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (1st Newly Revised Edition; Precautionary Prescription Clause Added) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 21. MAIBASTAN 5mg Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Each tablet contains 5mg or 10mg as pravastatin sodium. Additives: D-mannitol, hydroxypropylcellulose, silicic anhydride, magnesium stearate, ferric oxide Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate Maibastan 5mg: 100 tablets, 140 tablets, 700 tablets, 1000 tablets (PTP) Maibastan 5mg Tablets: 1000 tablets (Bottled) Maibastan 10mg: 100 tablets, 140 tablets, 700 tablets, 1000 tablets (PTP) Maibastan 10mg Tablets: 500 tablets (Bottled) Maibastan 5mg Tablet: White, diameter 6.5mm, thickness 2.2mm, weight 90mg Maibastan 10mg Tablet: Pinkish tablet with a mid-line, diameter 7.5mm, thickness 2.6mm , weight 140mg Manufacturer & Marketing Agent: Tohwa Yakuhin K.K. 2-11, Shinbashi-Cho, Kasadoma-city, Osaka 22. MEEK SIMVASTATIN Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination MEEK SIMVASTATIN Simvastatin 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 (15AM)296 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG CoA Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (1st Newly Revised Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 22. MEEK SIMVASTATIN Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent One tablet contains 5mg of simvastatin; Excipients: lactose, microcrystalline cellulose, anhydrous calcium hydrogen phosphate, hydroxypropylated starch, aspartame (containing L - phenylalanine), citrus oil, butyl hydroxyanisol, magnesium stearate Chemical Formula: C25H38O5; Chemical Name: (+)-(1S,3R,7S,8S,8aR)- 1,2,3,7,8,8a-Hexahydro-3,7-dimethyl-8-[2- [(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2- yl]ethyl]-1-naphtyl-2,2-dimethylbutanoate; Meek Simvastatin 5mg: 100, 280 and 500 tablets (PTP) White with one side as a two division line; Size: diameter 7.1mm; thickness 2.8mm; weight 140mg Marketing Agent: Meiji Seika Co. Ltd. 4-16 Kyobashi 2- chome, Chuo-ku, Tokyo 104-8002 Manufacturer: Kobayashi Kako K.K. 26-17, 2-Chome, Ichihime, Kanadu- Cho, Sakai-gun, Fukui, 919-0621 23. MEEK SIMVASTATIN Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination MEEK SIMVASTATIN Simvastatin 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 (15AM)296 Class 8 Hyperlipidemia, Familial hypercholesterolemia HMG CoA Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (1st Newly Revised Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 23. MEEK SIMVASTATIN Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent One tablet, contains 5mg of simvastatin; Excipients: Lactose, microcrystalline cellulose, anhydrous calcium hydrogen phosphate, hydroxypropylated starch, aspartame (containing L - phenylalanine), citrus oil, butyl hydroxyanisol, magnesium stearate Chemical Formula: C25H38O5; Chemical Name: (+)-(1S,3R,7S,8S,8aR)- 1,2,3,7,8,8a-hexahydro-3,7-dimethyl-8-[2- [(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2- yl]ethyl]-1-naphtyl-2,2-dimethylbutanoate; Meek Simvastatin 5mg: 100, 280 and 500 tablets (PTP) White with one side as a two division line; Size: diameter 7.1mm; thickness 2.8mm; weight 140mg Manufacturer & Marketing Agent Kobayashi Kako K.K. 26-17, 2-Chome, Ichihime, Kanadu- Cho, Sakai-gun, Fukui 919-0621 24. MEVALATION 5mg/10mg Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination MEVALATION Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00238000 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (2nd Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 24. MEVALATION 5mg/10mg Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Mevalation 5mg tablet contains: pravastatin sodium 5mg; Additives: lactose, cellulose, carboxymethylated starch sodium salt, calcium stearate; Mevalation 10mg tablet contains: pravastatin sodium 10mg. Additives: lactose, cellulose, carboxymethylated starch sodium salt, ferric oxide, calcium stearate Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate Mevalation 5mg: Tablets (PTP) in lots of 100, 700, 1000 and 500 (Bottled) Mevalation 10mg: Tablets (PTP) in lots of 100, 700, 1000 and 500 (Bottled) Mevalation 5mg: White tablet, Diameter 6.0mm, Thickness 2.4mm, Weight c.a. 90mg; Mevatorte 10mg: Pink tablet with one side line, Diameter 7.5mm, Thickness 2.8mm, Weight 140mg; Manufacturer & Marketing Agent: Choseido Seiyaku K.K. 92 Kou, Kokufu-cho, Tokushima-city, Tokushima 25. MEVALATION 5mg/10mg Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination MEVALATION Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00238 Class 8 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (2nd Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 25. MEVALATION 5mg/10mg Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Mevalation 5mg tablet contains: pravastatin sodium 5mg. Additives: lactose, cellulose, carboxymethylated starch sodium salt, calcium stearate; Mevalation 10mg tablet contains: pravastatin sodium 10mg. Additives: lactose, cellulose, carboxymethylated starch sodium salt, ferric oxide, calcium stearate Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate Mevalation 5mg: Tablets (PTP) in lots of 100, 700, 1000 and 500 (Bottled) Mevalation 10mg: Tablets (PTP) in lots of 100, 700, 1000 and 500 (Bottled) Mevalation 5mg: White tablet, Diameter 6.0mm, Thickness 2.4mm, Weight c.a. 90mg; Mevatorte 10mg: Pink tablet with one side line, Diameter 7.5mm, Thickness 2.8mm, Weight 140mg; Manufacturer: Choseido Seiyaku K.K. 92 Kou, Kokufu-cho, Tokushima-city, Tokushima Marketing Agent: Merck Hoei Co., Ltd. 6-8 Honmachi 2- Chome, Chuo-ku, Osaka 26. MEVALECT 5mg/10mg Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination MEVALECT Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00263000 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan June 2003 (1st Newly Revised Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 26. MEVALECT 5mg/10mg Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Mevalect 5mg tablet contains: pravastatin sodium 5mg. Additives: Lactose, microcrystalline cellulose, magnesium aluminum maleate, hydroxypropylcellulose, croscarmellose sodium, magnesium stearate; Mevalect 10mg tablet contains: pravastatin sodium 10mg. Additives: lactose, microcrystalline cellulose, magnesium aluminum maleate, hydroxypropylcellulose, croscarmellose sodium, ferric oxide, magnesium stearate Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-〔(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-〔(S)-2-methylbutyryloxy〕-1,2,6,7,8,8a- hexahydro-1-naphthyl〕heptanoate Mevalect 5mg:100 (PTP)、1000 (PTP) Mevalect 10mg:100 (PTP), 1000 (PTP) Mevalect 5mg: White tablet, Diameter 6.5mm, Thickness 2.2mm, Weight 90mg; Mevalect 10mg: Pink tablet with one side line, Diameter 7.5mm, Thickness 2.6mm, Weight 140mg; Manufacturer & Marketing Agent: Toryo-Yakuhin Kogyo K.K. 1-10-1, Yurakucho, Chiyoda- ku, Tokyo 27. MEVALECT 5mg/10mg Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination MEVALECT Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00263000 Class 8 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan June 2003 (1st Newly Revised Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 27. MEVALECT 5mg/10mg Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Mevalect 5mg tablet contains: pravastatin sodium 5mg. Additives: lactose, microcrystalline cellulose, magnesium aluminum maleate, hydroxypropylcellulose, croscarmellose sodium, magnesium stearate; Mevalect 10mg tablet contains: pravastatin sodium 10mg. Additives: lactose, microcrystalline cellulose, magnesium aluminum maleate, hydroxypropylcellulose, croscarmellose sodium, ferric oxide, magnesium stearate Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate Mevalect 5mg:100 (PTP)、1000 (PTP) Mevalect 10mg:100 (PTP), 1000 (PTP) Mevalect 5mg: White tablet, Diameter 6.5mm, Thickness 2.2mm, Weight 90mg; Mevalect 10mg: Pink tablet with one side line, Diameter 7.5mm, Thickness 2.6mm, Weight 140mg; Manufacturer: Toryo Yakuhin Kogyo K.K. 1-10-1, Yurakucho, Chiyoda- ku, Tokyo Marketing Agent: Nippon Hekisaru K.K. 1-10, 3-chome, Mita, Minato-ku, Tokyo Product Information continues on the next page 28. MEVALECT 5mg/10mg Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination MEVALECT Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00263000 Class 8 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan June 2003 (1st Newly Revised Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 28. MEVALECT 5mg/10mg Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Mevalect 5mg tablet contains: pravastatin sodium 5mg. Additives: lactose, microcrystalline cellulose, magnesium aluminum maleate, hydroxypropylcellulose, croscarmellose sodium, magnesium stearate; Mevalect 10mg tablet contains: pravastatin sodium 10mg. Additives: lactose, microcrystalline cellulose, magnesium aluminum maleate, hydroxypropylcellulose, croscarmellose sodium, ferric oxide, magnesium stearate Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate Mevalect 5mg:100 (PTP)、1000 (PTP) Mevalect 10mg: 100 (PTP), 1000 (PTP) Mevalect 5mg: White tablet, Diameter 6.5mm, Thickness 2.2mm, Weight 90mg; Mevalect 10mg: Pink tablet with one side line, Diameter 7.5mm, Thickness 2.6mm, Weight 140mg; Manufacturer: Toryo Yakuhin Kogyo K.K. 1-10-1, Yuraku- cho, Chiyoda-ku, Tokyo Marketing Agent: Nippon Garen K.K. 12- 18, 2-chome, Kawaguchi, Kawaguchi-city, Saitama 29. MEVALOCUT 5mg/10mg Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination MEVALOCUT Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00263000 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan June 2003 (1st Newly Revised Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 29. MEVALOCUT 5mg/10mg Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Mevalocut 5mg tablet contains: pravastatin sodium 5mg; Additives: Lactose, microcrystalline cellulose, magnesium aluminum maleate, hydroxypropylcellulose, croscarmellose sodium, magnesium stearate; Mevalocut 10mg tablet contains: pravastatin sodium 10mg; Additives: Lactose, microcrystalline cellulose, magnesium aluminum maleate, hydroxypropylcellulose, croscarmellose sodium, ferric oxide, magnesium stearate Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl] heptanoate Mevalocut 5mg:100, 500, 1000 (PTP); 500 (bottled) Mevalocut 10mg:100, 500, 1000 (PTP); 500 (bottled) Mevalocut 5mg: White tablet, Diameter 6.6mm, Thickness 2.1mm, Weight 90mg; Mevalocut 10mg: Pink tablet with one side line, Diameter 7.6mm, Thickness 2.5mm, Weight 140mg; Manufacturer & Marketing Agent: Toyo Pharma K.K. 287-1, Shimocho, Moroe-machi, Kanazawa-shi, Ishikawa 30. MEVALOTIN 5mg/10mg Tablet, 0.5%/1.0% Granules Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination MEVALOTIN(r) Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category September 2001 21300AMZ00549 Class 7 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan October 2003 (8th Newly Revised Edition) Prescription Medicine September 2001 October 1989 Product Information continues on the next page 30. MEVALOTIN 5mg/10mg Tablet, 0.5%/1.0% Granules Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Mevalotin 5mg tablet contains: pravastatin sodium 5mg; Additives: hydroxypropylcellulose, low molecular weight microcrystalline hydroxypropylcellulose, magnesium aluminium silicate, lactose, magnesium stearate; Mevalotin 10mg tablet contains: pravastatin sodium 10mg; Additives: hydroxypropylcellulose, low molecular weight microcrystalline hydroxypropylcellulose, magnesium aluminium silicate, microcrytalline cellulose, lactose, ferric oxide, magnesium stearate Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate Mevalotin 5mg: 100 tablets, 140 (10 x 14 tablets), 500 tablets, 700 (50 x 14 tablets)- PTP; 1,000 tablets (PTP/Bottled) Mevalotin 10mg: 100 tablets, 140 (10 x 14 tablets), 300 tablets, 700 (50 x 14 tablets), 1000 tablets - PTP; 500 tablets (PTP/Bottled) Mevalotin 0.5% granules:100g (bottled), 1g504 sachets Mevalotin 5mg: White tablet, Diameter 6.5mm, Thickness 2.1mm, Weight 90mg; Mevalotin 10mg: Pink tablet with one side line, Diameter 7.5mm, Thickness 2.6mm, Weight 140mg; Manufacturer & Marketing Agent: Sankyo K.K., 3-5-1 Honmachi, Nihonbashi, Chuo-ku, Tokyo Product Information continues on the next page 30. MEVALOTIN 5mg/10mg Tablet, 0.5%/1.0% Granules Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent 1.0g of Mevalotin 0.5% granules contains: pravastatin sodium 5mg; hydroxypropylcellulose, low molecular weight microcrystalline hydroxypropylcellulose, magnesium aluminium silicate, lactose, magnesium stearate; 1.0g of Mevalotin 1% granules contains: pravastatin sodium 10mg; hydroxypropylcellulose, low molecular weight microcrystalline hydroxypropylcellulose, magnesium aluminium silicate, microcrytalline cellulose, lactose, ferric oxide, magnesium stearate Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate Mevalotin 0.5% granules:100g (bottled), 1g504 sachets Mevalotin 1% granules: 100g (bottled) Manufacturer & Marketing Agent: Sankyo K.K., 3-5-1 Honmachi, Nihonbashi, Chuo-ku, Tokyo 31. MEVAN 5mg/10mg Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination MEVAN Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21300AMZ00549 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor; Hypercholesterolemia Treatment Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan June 2003 (1st Newly Revised Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 31. MEVAN 5mg/10mg Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Mevan 5mg tablet contains: pravastatin sodium 5mg; Additives: lactose, cellulose, hydroxypropylcellulose, magnesium stearate; Mevan 10mg tablet contains: pravastatin sodium 10mg; Additives: lactose, cellulose, hydroxypropylcellulose, ferric oxide, magnesium stearate Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate Mevan 5mg: 100 (10 tablets x 10; PTP), 500 (10 tablets x 50; PTP), 500 tablets (bottled), 700 (14 tablets x 50; PTP) Mevan 10mg: 100 (10 tablets x 10; PTP), 140 (14 tablets x 10; PTP), 500 (10 tablets x 50; PTP), 500 tablets (bottled) 700 (14 tablets x 50; PTP) Mevan 5mg: White tablet, Diameter 6.0mm, Thickness 2.5mm, Weight 90mg; Mevan 10mg: Pink tablet with one side line, Diameter 7.0mm, Thickness 2.9mm, Weight 140mg; Manufacturer & Marketing Agent: Nippon Iyakuhin Kogyo K.K. 6-21, 1-chome, Sougawa, Toyama- city, Toyama 32. MEVARICH 5mg/10mg Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination MEVARICH Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00253000 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (1st Newly Revised Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 32. MEVARICH 5mg/10mg Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Mevarich 5mg tablet contains: pravastatin sodium 5mg. Additives: Lactose, maize starch, microcrystalline cellulose, sodium hydrogen phosphate, carmellose calcium, ferric oxide, magnesium stearate; Mevalation 10mg tablet contains: pravastatin sodium 5mg. Additives: lactose, cellulose, carboxymethylated starch sodium salt, ferric oxide, calcium stearate Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate Mevarich 5mg: 100 (10 PTP sheets of 10 tablets), 500 (50 PTP sheets of 10 tablets), 500 tablets, 700 (50 PTP sheets of 14 tablets), 1000 (100 PTP sheets of 10 tablets) Mevarich 10mg: 100 (10 PTP sheets of 10 tablets), 500 (50 PTP sheets of 10 tablets), 500 tablets, 700 (50 PTP sheets of 14 tablets), 1000 (100 PTP sheets of 10 tablets) Mevarich 5mg: White tablet, Diameter 6.0mm, Thickness 1.9mm, Weight c.a. 70mg; Mevarich 10mg: Pink tablet with one side line, Diameter 7.0mm, Thickness 2.6mm, Weight 120mg; Manufacturer: Nisshin Seiyaku K.K. 1331 Aza Fujidan, O- aza Syouge, Tendou- city, Yamagata Marketing Agent: Kaken Seiyaku K.K. 28-8. 2-Chome, Honkomagome, Bunjyo-ku, Tokyo 33. MEVARICH 5mg/10mg Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination MEVARICH Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00253000 Class 8 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan June 2003 (1st Newly Revised Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 33. MEVARICH 5mg/10mg Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Mevarich 5mg tablet contains: pravastatin sodium 5mg. Additives: lactose, maize starch, microcrystalline cellulose, sodium hydrogen phosphate, carmellose calcium, ferric oxide, magnesium stearate; Mevalation 10mg tablet contains: pravastatin sodium 10mg. Additives: lactose, cellulose, carboxymethylated starch sodium salt, ferric oxide, calcium stearate Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate Mevarich 5mg: 100 (10x10 tablets), 500 (50x10 tablets), 500 tablets, 700 (50x14 tablets), 1000 (100x10 tablets) (PTP), 1000 tablets (Bottled) Mevarich 10mg: 100 (10x10 tablets), 500 (50x10 tablets), 500 tablets, 700 (50x14 tablets), 1000 (100x10 tablets), 1000 tablets (Bottled) Mevarich 5mg: White tablet, Diameter 6.0mm, Thickness 1.9mm, Weight c.a. 70mg; Mevarich 10mg: Pink tablet with one side line, Diameter 7.0mm, Thickness 2.6mm, Weight 120mg; Manufacturer & Marketing Agent: Nisshin Seiyaku K.K. 1331 Aza Fujidan, O- aza Syouge, Tendou- city, Yamagata 34. MEVASROLIN 10mg Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination MEVASROLIN Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00350000 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan June 2003 (1st Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 34. MEVASROLIN 10mg Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Each tablet contains: pravastatin sodium 10mg. Additives: lactose, microcrystalline cellulose, croscarmellose sodium, magnesium stearate, ferric oxide, yellow ferric oxide Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate Mevasrolin 10mg tablet: 100, 500 Tablets Mevasrolin 10mg tablet is pink in color and has a line on one side with the identifying symbol TSU755. Diameter 7.5mm、Thickness 2.4mm, Weight 140mg Manufacturer & Marketing Agent: Turuhara Seiyaku K.K. 16-1, 1 Chome, Toyoshima-kita, Ikeda-city, Osaka 35. MEVASTAN 10 Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination MEVASTAN Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00265 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (2nd Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 35. MEVASTAN 10 Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Each tablet contains: pravastatin sodium 10mg; Additives: aspartame, yellow ferric oxide, polyplasdone XL, calcium stearate, ferric oxide, Japan Pharmacopoeia (JP) grade magnesium stearate, JP grade D- mannitol, flavoring Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate Mevastan 10mg: 100 (10 tablets x 10), 500 tablets (10 tablets x 50) (PTP) Mevastan 10mg Tablet: Pink, Diameter 8.0mm, Thickness 3.6mm, Weight 180mg Manufacturer: Mohann-Yakuhin Laboratory K.K., 4-13-5, Nishi-sugamo, Toshima-ku, Tokyo Marketing Agent: Kyowa Hakkou Kogyo K.K. 1-6-1, Otemachi, Chiyoda-ku, Tokyo 36. MEVATORTE 5/10 Tablet & Granules Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination MEVATORTE Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00329 Class 8 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan October 2003 (3rd Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 36. MEVATORTE 5/10 Tablet & Granules     Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Each tablet of Mevatorte 5 contains: pravastatin sodium 5mg; Additives: lactose, cellulose, hydroxypropylcellulose, hydroxypropylmethylcellu lose, magnesium stearate; Mevatorte 10: pravastatin sodium 10mg; Additives: Lactose, cellulose, hydroxypropylcellulose, hydroxypropylmethylcellu lose, ferric oxide, magnesium stearate; & Mevatorte Granules: pravastatin sodium 10mg, hydroxypropylcellulose, hydroxypropylmethylcellu lose, ferric oxide, talc, magnesium stearate. Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate Mevatorte 5/10mg 100 tablets; PTP (10 tablets x 10); 5/10 mg 700 tablets; PTP (14 tablets x 50); 5/10 mg 1000 tablets; PTP (10 tablets x 100); 5/10 mg 500 tablets (Bottled) Mevatorte 1% 100g Granules Mevatorte 5mg: White tablet, Diameter 6.5mm, Thickness 2.2mm, Weight c.a. 90mg; Mevatorte 10mg: Pink tablet with one side line, Diameter 7.5mm, Thickness 2.6mm, Weight c.a. 140mg; Mevatorte Granules: Pink Manufacturer & Marketing Agent: Taisyo Yakuhin Kogyo K.K. 3, Ohara-Ichiba, Kouka-chou, Kouka- gun, Shiga 37. MINDOROTIN 5mg/10mg Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination MINDOROTIN Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00316000 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (2nd Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 37. MINDOROTIN 5mg/10mg Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Each 5mg tablet contains 5mg as pravastatin sodium. Additives: microcrystalline cellulose, lactose, calcium stearate, sodium lauryl sulfate, sodium phosphate dibasic, croscarmellose sodium, povidone, light anhydrous silicic acid, magnesium stearate. Each 10mg tablet contains 10mg as pravastatin sodium. Additives: microcrystalline cellulose, lactose, calcium stearate, sodium lauryl sulfate, sodium phosphate dibasic, croscarmellose sodium, povidone, ferric oxide, light anhydrous silicic acid, magnesium stearate. Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate Mindorotin 5mg: 100 tablets, 500 tablets (PTP); 1000 tablets (bottled) Mindorotin 10mg: 100 tablets, 500 tablets (PTP); 500 tablets (bottled) Mindorotin 5mg Tablet: White, Diameter 6.0mm, Thickness 2.4mm, Weight 90mg Mindorotin 10mg Tablet: Pink, Diameter 7.0mm、Thickness 2.4mm, Weight 100mg Manufacturer & Marketing Agent: Maruko Yakuhin K.K. 5-17, 1-chome, Kodama, Nishi-ku, Nagoya 38. OHARA SIMVASTATIN Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination OHARA SIMVASTATIN Simvastatin 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00327000 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG CoA Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan June 2003 (1st Newly Revised Edition) Prescription Medicine July 2003 July 2003    Product Information continues on the next page 38. OHARA SIMVASTATIN Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent One tablet, contains 5mg of simvastatin Chemical Formula: C25H38O5; Chemical Name: (+)-(1S,3R,7S,8S,8aR)- 1,2,3,7,8,8a-Hexahydro-3,7-dimethyl-8-[2- [(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2- yl]ethyl]-1-naphtyl-2,2-dimethylbutanoate; Ohara Simvastatin 5mg: (PTP), 100 tablets ( 10 tablet 10 ) 500 tablets ( 10 tablet 50 ), 700 tablets (14 tablet 50 ) White with a line marking on one side; Size: diameter 6.5mm; thickness 2.3mm; weight 100mg Manufacturer: Yoshindo K. K. 3697-8, Haginoshima, Fuchu-machi, Nei- gun, Toyama Marketing Agent: Nippon Chemiphar Co., Ltd. 2-2-3, Iwamoto-cho, Chiyoda-ku, Tokyo, 101-8678 39. OHARA SIMVASTATIN Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination OHARA SIMVASTATIN Simvastatin 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00327000 Class 8 Hyperlipidemia, Familial hypercholes terolemia HMG CoA Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan June 2003 (1st Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 39. OHARA SIMVASTATIN Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent One tablet, contains 5mg of simvastatin Chemical Formula: C25H38O5; Chemical Name: (+)-(1S,3R,7S,8S,8aR)- 1,2,3,7,8,8a-Hexahydro-3,7-dimethyl-8-[2- [(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2- yl]ethyl]-1-naphtyl-2,2-dimethylbutanoate Ohara Simvastatin 5mg: (PTP), 100 tablets ( 10 tablet 10 ) 500 tablets ( 10 tablet 50 ), 700 tablets ( 14 tablet 50 ) White with a line marking on one side; Size: diameter 6.5mm; thickness 2.3mm; weight 100mg Manufacturer: Ohara Chemical Industries, Ltd. 43-1 Oharaichiba Koka-Cho, Koka-Gun Shiga, 520-3433 Marketing Agent: Takata Seiyaku 13-10, 2-chome, Trigoe, Taito-ku Tokyo 40. OHARA SIMVASTATIN Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination OHARA SIMVASTATIN Simvastatin 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00327000 Class 8 Hyperlipidemia Familial hypercholesterolemia HMG CoA Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan June 2003 (1st Newly Revised Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 40. OHARA SIMVASTATIN Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent One tablet, contains 5mg of simvastatin Chemical Formula: C25H38O5; Chemical Name: (+)-(1S,3R,7S,8S,8aR)- 1,2,3,7,8,8a-Hexahydro-3,7-dimethyl-8-[2- [(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2- yl]ethyl]-1-naphtyl-2,2-dimethylbutanoate Ohara Simvastatin 5mg: (PTP), 100 tablets ( 10 tablet 10 ) 500 tablets ( 10 tablet 50 ), 700 tablets ( 14 tablet 50 ) White with a line marking on one side; Size: diameter 6.5mm; thickness 2.3mm; weight 100mg Manufacturer & Marketing Agent: Ohara Chemical Industries, Ltd. 43-1 Oharaichiba Koka-Cho, Koka-Gun Shiga, 520-3433 41. PRAVALON 5/10 Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination PRAVALON Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00177000 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (1st Newly Revised Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 41. PRAVALON 5/10 Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Effective ingredient in 1 5mg tablet: 5mg of pravastatin sodium. Additives: Lactose, maize starch, hydroxypropylcellulose, magnesium stearate Effective ingredient in 1 10mg tablet: 10mg of pravastatin sodium. Additives: Lactose, maize starch, hydroxypropylcellulose, ferric oxide, magnesium stearate Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate Pravalon 5 PTP: 56 tablets (14 tablet 4),100 tablets (10 tablet 10), 500 tablets (10 tablet 50), 700 tablets (14 tablet 50), Bottled: 1,000 tablets Pravalon 10 PTP: 56 tablets (14 tablet 4),100 tablets (10 tablet 10), 500 tablets (10 tablet 50), 700 tablets (14 tablet 50), Bottled: 500 tablets 10mg Tablet: Pinkish red, half line on one side, odorless slightly bitter tasting, 8.0mm diameter, 2.4mm thickness & 150mg weight Marketing Agent: Teikoku Medic K. K. 9-19 Tosawamachi, Nihonbashi, Chuo-ku, Tokyo Manufacturer: Daito K.K. 326 Yokamachi, Toyama-shi, Toyama 939-8221 42. PRAVAMATE 5mg/10mg Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination PRAVAMATE Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00325000 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan June 2003 (1st Newly Revised Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 42. PRAVAMATE 5mg/10mg Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Effective ingredient in 1 5mg tablet: 5mg of pravastatin sodium Effective ingredient in 1 10mg tablet: 10mg of pravastatin sodium Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate Pravamate 5mg PTP Packaging: 100 tablets (10 tablets 10), 500 (10 tablet x 50), 700 tablets (14 tablet 50), 1000 tablets (10 tablet x 100) Bottled Packaging: 1000 tablets Pravamate 10mg PTP Packaging: 100 tablets (10 tablets 10), 300 (10 tablets x 30), 500 (10 tablets x 50), 700 tablets (14 tablet 50), 1000 tablets (10 tablets x 100), Bottled Packaging: 500 tablets 5mg Tablet: 6.5mm diameter, 2.4mm thickness & 100mg weight 10mg Tablet: 7.5mm diameter, 2.4mm thickness & 130mg weight Manufacturer & Marketing Agent: Ohara Chemical Industries Ltd. 43-1 Oharaichiba Kouka-cho, Kouka- Gun Shiga, 520-3433 43. PRAVASTAN Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination PRAVASTAN Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00154000 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (1st Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 43. PRAVASTAN Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Effective ingredient in 1 5mg tablet: 5mg of pravastatin sodium. Additives: sodium caramellose, magnesium stearate, cellulose, lactose; Effective ingredient in 1 10mg tablet: 10mg of pravastatin sodium. Additives: Yellow ferric oxide, caramellose sodium, ferric oxide, magnesium stearate, cellulose, lactose Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate Pravastan 5mg PTP Packaging: 100 tablets (10 tablets 10), 500 tablets (10 tablet 50), 700 tablets (14 tablet 50) Bottled Packaging : 1000 tablets Pravastan 10mg PTP Packaging: 100 tablets (10 tablets 10), 500 tablets (10 tablet 50), 700 tablets (14 tablet 50) Bottled Packaging : 500 tablets White tablet 5 mg: 6.5mm diameter, 2.0mm thickness & 90mg weight 10mg: 7.5mm diameter, 3.0mm thickness & 140mg weight Manufacturer & Marketing Agent: Japan Yakuhin Kogyo K.K. 2-3 Ishimotomachi 2- Chome, Chiyoda-ku, Tokyo 44. PRAVASTAN 5/10 Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination PRAVASTAN Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00154000 Class 8 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (1st Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 44. PRAVASTAN 5/10 Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Effective ingredient in 1 5mg tablet: 5mg of pravastatin sodium. Additives: sodium caramellose, magnesium stearate, cellulose, lactose Effective ingredient in 1 10mg tablet: 10mg of pravastatin sodium. Additives: Yellow ferric oxide, caramellose sodium, ferric oxide, magnesium stearate, cellulose, lactose Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate Pravastan 5 mg PTP Packaging: 100 tablets (10 tablets 10), 500 tablets (10 tablet 50), 700 tablets (14 tablet 50) Bottled Packaging: 1000 tablets Pravastan 10 mg PTP Packaging: 100 tablets (10 tablets 10), 500 tablets (10 tablet 50), 700 tablets (14 tablet 50) Bottled Packaging: 500 tablets 5mg: 6.5mm diameter, 2.0mm thickness & 90mg weight 10mg: 7.5mm diameter, 3.0mm thickness & 140mg weight Manufacturer: Japan Yakuhin Kogyo K.K. 2-3 Iwamotomachi 2- Chome, Chiyoda-ku, Tokyo, 101-8678 Marketing Agent: Chemiphar K.K. 2-2-3, Iwamoto-cho, Chiyoda-ku, Tokyo, 101-8678 45. PRAVASTATIN SODIUM 5mg/10mg Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination PRAVASTATIN SODIUM Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00281 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (1st Newly Revised Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 45. PRAVASTATIN SODIUM 5mg/10mg Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Effective ingredient in 1 tablet: 5mg/10mg of pravastatin sodium Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyrylox]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate Pravastatin Sodium 5mg PTP Packaging: 100 tablets (10 tablets 10), 500 tablets (10 tablets 50), 700 tablets (14 tablets 50) Bottled Packaging : 500 tablets Pravastatin Sodium 10 mg PTP Packaging: 100 tablets (10 tablets 10), 500 tablets (10 tablet 50), 700 tablets (14 tablet 50) Bottled Packaging : 500 tablets Odourless white tablet, slightly bitter tasting. (No tablet size specification) Manufacturer & Marketing Agent: Yoshindo K.K, 3697-8, Haginoshima, Fuchu- machi , Nei-gun, Toyama 46. PRAVATIN 5/10 Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination PRAVATIN Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00354000 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (2nd Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 46. PRAVATIN 5/10 Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Effective ingredient in 1 5mg tablet: 5mg of pravastatin sodium. Additives: magnesium stearate, lactose, hydroxypropylcellulose, meta-citric acid, magnesium aluminate Effective ingredient in 1 10mg tablet: 10mg of pravastatin sodium Additives: ferric oxide, magnesium stearate, lactose, hydroxypropylcellulose, meta-citric acid, magnesium aluminate Chemical Formula: C23H35NaO7; Chemical Name: Sodium(+)-(3R,5R)-3,5- dihydroxy-7-[(1S,2S,6S,8S,8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1,2,6,7,8,8a- hexahydro-1-naphthyl]heptanoate Pravatin 5 PTP: 100 (10 tablets x 10), 700 (14 tablets x 50), 1000 (10 tablets x 100) Bottled: 1000 tablets Pravatin 10 PTP: 100 (10 tablets x 10), 700 (14 tablets x 50), 1000 (10 tablets x 100) Bottled: 1000 tablets 5mg Tablet: 6.5mm diameter, 2.1mm thickness & 85mg weight 10mg Tablet: 7.0mm diameter, 2.4mm thickness & 110mg weight Manufacturer & Marketing Agent: Sawai Seiyaku K.K. 4-25, Akagawa 1- chome, Asahi-ku, Osaka 535-0005 47. RAMIAN 5mg Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination RAMIAN(r) Simvastatin 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00332000 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan June 2003 (2nd Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 47. RAMIAN 5mg Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent Ramian 5mg tablet contains: simvastatin 5mg. Additives: citric acid, microcrystalline cellulose, magnesium stearate, maize starch, lactose, hydroxypropylmethylcellu lose 2910, butylhydroxyanisol Chemical Formula: C25H38O5; Chemical Name: (+)-(1S,3R,7S,8S,8aR)- 1,2,3,7,8,8a-Hexahydro-3,7-dimethyl-8-[2- [(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2- yl]ethyl]-1-naphthyl 2,2-dimethylbutanoate Ramian 5mg: 100 (10 tablets x 10) 500 tablets (bottled) 1000 (10 tablets x 100) Ramian 5mg: White tablet, Diameter 6.5mm, Thickness 2.3mm, Weight 100mg Manufacturer: Taisyo Yakuhin Kogyo K.K. 3, Ohara-Ichiba, Kouka-chou, Kouka- gun, Shiga Marketing Agent: Teikoku Zouki Seiyaku K.K. 5-1, 2-chome, Shibaura, Minato-ku, Tokyo 48. SIMVAMERCK Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination SIMVAMERCK Simvastatin 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00349 Class 7-2 Hyperlipidemia, Familial hypercholesterolemia HMG CoA Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (1st Newly Revised Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 48. SIMVAMERCK Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent One tablet, contains 5mg of simvastatin; Excipients: lactose, hydropropylated starch, sodium croscarmellose, t- butylhydroxytoluene, magnesium stearate Chemical Formula: C25H38O5; Chemical Name: (+)-(1S,3R,7S,8S,8aR)- 1,2,3,7,8,8a-Hexahydro-3,7-dimethyl-8-[2- [(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2- yl]ethyl]-1-naphtyl-2,2-dimethylbutanoate Simvamerck Tablet 5mg Bottled: 500 tablets PTP: 100 & 500 tablets White with one side as a two division line; Size: diameter 6.5mm; thickness 2.3mm; weight 100mg Manufacturer: Mohann-Yakuhin Laboratory K.K., 4-13- 5, Nishi-sugamo, Toshima-ku, Tokyo Marketing Agent: Merck Hoei K.K., 6-8 Honmachi 2- Chome, Chuo-ku, Osaka 49. SINSTATIN Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination SINSTATIN Simvastatin 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00280 Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG CoA Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (1st Newly Revised Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 49. SINSTATIN Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent 1 tablet, contains 5mg of simvastatin as an additive, contains butylhydroxyanisol Chemical Formula: C25H38O5; Chemical Name: (+)-(1S,3R,7S,8S,8aR)- 1,2,3,7,8,8a-Hexahydro-3,7-dimethyl-8-[2- [(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2- yl]ethyl]-1-naphtyl-2,2-dimethylbutanoate PTP: 100 (10 Tablets x 10), 500 (10 Tablets x 50), 700 (14 Tablets x 50) Bottled: 500 Tablets White with a line marking on one side Manufacturer & Marketing Agent: Yoshindo K.K. 3697-8, Ogishima, Haginoshima, Fuchu- machi , Nei-gun, Toyama 50. SINSTATIN Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination SINSTATIN Simvastatin 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00280 Class 8 Hyperlipidemia Familial hypercholesterolemia HMG CoA Reductase Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan July 2003 (1st Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 50. SINSTATIN Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent One tablet, contains 5mg of simvastatin as an additive, contains butylhydroxyanisol Chemical Formula: C25H38O5; Chemical Name: (+)-(1S,3R,7S,8S,8aR)- 1,2,3,7,8,8a-Hexahydro-3,7-dimethyl-8-[2- [(2R,4R)-tetrahydro-4-hydroxy-6-oxo-2H-pyran-2- yl]ethyl]-1-naphtyl-2,2-dimethylbutanoate White with a line marking on one side; Size: diameter 6.0mm; thickness 2.6mm; weight 100mg Manufacturer: Yoshindo K. K. 3697-8, Haginoshima, Fuchu-machi , Nei- gun, Toyama Marketing Agent: Nippon Chemiphar Co., Ltd. 2-2-3, Iwamoto-cho, Chiyoda-ku, Tokyo, 101-8678 51. TATSUPLAMIN 5mg/10mg Tablet Brand Generic Name Japan Standard Commodity Classification Number Period for Reexamination TATSUPLAMIN Pravastatin Sodium 872189 6 years Approval Date/Number Approval Classification Approved Indication(s) Therapeutic Category July 2003 21500AMZ00288000 (5mg) 21500AMZ00289000(10mg) Class 7-2 Hyperlipidemia Familial hypercholesterolemia HMG Co-A Enzyme Inhibitor Package Insert Revision Regulatory Classification(s) Listing in the National Health Insurance Price List Market Launch in Japan June 2003(1st Newly Revised Edition) Prescription Medicine July 2003 July 2003 Product Information continues on the next page 51. TATSUPLAMIN 5mg/10mg Tablet Bulk Formulation Chemical Characterization Packaging & Formulation Specification Manufacturer/ Marketing Agent One tablet, contains 5mg or 10mg of pravastatin sodium; Excipients: hydroxypropylcellulose, microcrystalline hydroxypropylcellulose, cellulose, magnesium alumina silicate , lactose, magnesium stearate Chemical Formula: C23H35NaO7 Chemical Name: Sodium (+)-(3R, 5R)-3, 5- dihydroxy-7-[(1S, 2S, 6S, 8S, 8aR)-6-hydroxy-2- methyl-8-[(S)-2-methylbutyryloxy]-1, 2, 6, 7, 8, 8a-hexahydro-1-naphthyl] heptanoate Tatsuplamin Tablet 5mg: 100 (PTP) 500 (PTP), 1000 (PTP & Bottled) Tatsuplamin Tablet 10mg: 100 (PTP), 500 (PTP), 1000 (PTP & Bottled) Solid form: White crystalline solid Tatsuplamin Tablet 5mg Size: Diameter 6.5mm, Thickness 2.1mm, Weight 90 mg; Tatsuplamin Tablet 10mg Size: Diameter 7.5mm, Thickness 2.6mm, Weight 140mg Manufacturer & Marketing Agent: Tasumi Kagaku K.K., 406 3 Chome, Hisayasu, Kanazawa, Ishikawa, 921-8164 Disclaimer This publication is based on information obtained through in-house research and from sources available to public and it is not a complete analysis of every material fact. 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Statin pleiotropism refers to the non-lipid lowering effects, such as endothelial function, inflammation, coagulation and plaque stability. On the basis of the NHI reimbursement prices in 2003; in-house research. Withdrawn from the market in 2001 - see more info. Modified from the Attached Table 2-1, MHW, Pharmaceutical Affairs Bureau Notification No. 698 dated May 30, 1980. MHW, Pharmaceutical Affairs Bureau Notification No. 698 (May 30, 1980) describes nine different approval classifications of prescription medicinal products in Japan however only those classifications relevant to the Statin class of medicines have been included here: Class 1 - Medicines with new active ingredients; Class 7 - Medicines with additional dosage forms; Class 7-2 - Medicines with similar formulations; Class 8 - Miscellaneous July 2003 was when the Japan Patent for Mevalotin(r) expired Mevalotin(r) and Mevatorte granules Mevalotin(r) was commercially launched as early as October 1989, in September 2003 0.5%/1.0% Mevalotin(r) granules was approved as an additional formulation (Class 7) All in Japan Statins Copyright (c) 2001-2004 by JKS LLC - 3 - Copyright (c) 2001-2004 by JKS LLC - 4 - All in Japan Statins Copyright (c) 2001-2004 by JKS LLC - 7 - All in Japan Statins Copyright (c) 2001-2004 by JKS LLC - 8 - All in Japan Statins Copyright (c) 2001-2004 by JKS LLC - 10 - All in Japan Statins Copyright (c) 2001-2004 by JKS LLC - 12 - All in Japan Statins Copyright (c) 2001-2004 by JKS LLC - 15 - All in Japan Statins Copyright (c) 2001-2004 by JKS LLC - 118 -