A NICHE
MARKET-LEVOTHYROXINE
TABLET
May 2004
Innovative Companies Inc. (GORX) filed a patent application on a novel method to
stabilize the drug levothyroxine on January 12, 2004. Levothyroxine sold in oral tablet
dosage form is used to treat thyroid-related conditions. The major players in the
manufacturing of levothyroxine tablets include Abbott, Alara Pharm, GenPharm, Jones
Pharma, Lloyd, Mylan, Stevens J and Vintage Pharms (Table 1). The retail sales for all
levothyroine sodium tablets were about $1.1 billion in 2002. However, levothyroxine
sodium is hygroscopic and degrades rapidly under conditions of high humidity or
light. Though a few patents for stabilizing levothyroxine have been filed and issued
(Attachment 1), instability with the commerical products still occasionally occured in
the last four years (Table 2).
Since there is a stabiity problem associated with the active ingredient and there are
already a few patents issued for the stabilization methods, it represents a barrier for
most generic companies without an unique/non-infringing technology get into this
market.
TABLE 1
MAJOR PLAYERS IN THIS AREA
ABBOTT-----------SYNTHROID (BX) ----------------------------------------Oral Tablets
Alara Pharm-------Levo-T (BX) ----------------------------------------------Oral Tablets
GenPharm---------Novothyrox (BX)------------------------------------------Oral Tablets
Jones Pharma-----Levoxyl (BX) ---------------------------------------------Oral Tablets
Lloyd----------------Thyro-Tabs (BX) ----------------------------------------Oral Tablets
Mylan----------------Levothyroxine Sodium Tablet (AB)------------------Oral Tablets
Stevens J.----------Levothyroxine Sodium Tablet (AB)------------------Oral Tablets
Vintage Pharms --Levolet (BX)----------------------------------------------Oral Tablets
TABLE 2
RECALLS (1999-2004) RELATED TO SUBPOTENCY/STABILITY ISSUES
DATE PRODUCTS COMPANY
July 25, 2001 Levothyroxine Vintage Pharmaceuticals, Inc.
sodium tablets
October 17, 2001 Levoxyl King Pharmaceuticals, Inc.
December 29, 1999 Levothroid Forest Pharmaceuticals, Inc.
April 17, 2002 Levothyroxine Vintage Pharmaceuticals, Inc.
ATTACHMENT 1
PATENTED METHODS FOR LEVOTHYROXINE STABILIZATION
Methods used to stabilize levothyroxine in medications have been studied more than
a decade. The leading group in this area is Chen et al (US Patent 5,225,204, July 6,
1993). They stabilized levothyroxine sodium by complex formation using
polyvinylpyrrolidone. Later, Groenewoud et al (US Patents 5,635,209 and 6,190,696
Vintage Pharmaceuticals, Inc.) stabilized levothyroxine sodium using iodide as a
stabilizing excipient. Mitra et al (US Patents 5,955,105 and 6,056,975) stabilized the
compound with a mixture of glycine, a carbohydrate and an inorganic salt. Frontanes,
et al (US Patent 6,399,101) used silicified microcrystalline cellulose to stabilize the
drug. Schreder, et al (US Patent 6,491,946) used a mixture of potassium iodide,
microcrystalline cellulose and binding agent to prepare a stable preparation of
levothyroxine. While, Franz et al (US Patent 6,555,581, Jones Pharma Inc.) prepared a
stable composition using beta-form of microcrystalline cellulose and disintegrant
HOME
MARKET-LEVOTHYROXINE
TABLET
May 2004
Innovative Companies Inc. (GORX) filed a patent application on a novel method to
stabilize the drug levothyroxine on January 12, 2004. Levothyroxine sold in oral tablet
dosage form is used to treat thyroid-related conditions. The major players in the
manufacturing of levothyroxine tablets include Abbott, Alara Pharm, GenPharm, Jones
Pharma, Lloyd, Mylan, Stevens J and Vintage Pharms (Table 1). The retail sales for all
levothyroine sodium tablets were about $1.1 billion in 2002. However, levothyroxine
sodium is hygroscopic and degrades rapidly under conditions of high humidity or
light. Though a few patents for stabilizing levothyroxine have been filed and issued
(Attachment 1), instability with the commerical products still occasionally occured in
the last four years (Table 2).
Since there is a stabiity problem associated with the active ingredient and there are
already a few patents issued for the stabilization methods, it represents a barrier for
most generic companies without an unique/non-infringing technology get into this
market.
TABLE 1
MAJOR PLAYERS IN THIS AREA
ABBOTT-----------SYNTHROID (BX) ----------------------------------------Oral Tablets
Alara Pharm-------Levo-T (BX) ----------------------------------------------Oral Tablets
GenPharm---------Novothyrox (BX)------------------------------------------Oral Tablets
Jones Pharma-----Levoxyl (BX) ---------------------------------------------Oral Tablets
Lloyd----------------Thyro-Tabs (BX) ----------------------------------------Oral Tablets
Mylan----------------Levothyroxine Sodium Tablet (AB)------------------Oral Tablets
Stevens J.----------Levothyroxine Sodium Tablet (AB)------------------Oral Tablets
Vintage Pharms --Levolet (BX)----------------------------------------------Oral Tablets
TABLE 2
RECALLS (1999-2004) RELATED TO SUBPOTENCY/STABILITY ISSUES
DATE PRODUCTS COMPANY
July 25, 2001 Levothyroxine Vintage Pharmaceuticals, Inc.
sodium tablets
October 17, 2001 Levoxyl King Pharmaceuticals, Inc.
December 29, 1999 Levothroid Forest Pharmaceuticals, Inc.
April 17, 2002 Levothyroxine Vintage Pharmaceuticals, Inc.
ATTACHMENT 1
PATENTED METHODS FOR LEVOTHYROXINE STABILIZATION
Methods used to stabilize levothyroxine in medications have been studied more than
a decade. The leading group in this area is Chen et al (US Patent 5,225,204, July 6,
1993). They stabilized levothyroxine sodium by complex formation using
polyvinylpyrrolidone. Later, Groenewoud et al (US Patents 5,635,209 and 6,190,696
Vintage Pharmaceuticals, Inc.) stabilized levothyroxine sodium using iodide as a
stabilizing excipient. Mitra et al (US Patents 5,955,105 and 6,056,975) stabilized the
compound with a mixture of glycine, a carbohydrate and an inorganic salt. Frontanes,
et al (US Patent 6,399,101) used silicified microcrystalline cellulose to stabilize the
drug. Schreder, et al (US Patent 6,491,946) used a mixture of potassium iodide,
microcrystalline cellulose and binding agent to prepare a stable preparation of
levothyroxine. While, Franz et al (US Patent 6,555,581, Jones Pharma Inc.) prepared a
stable composition using beta-form of microcrystalline cellulose and disintegrant
HOME
PHARMCEUTICAL
INDUSTRY
Foundamental
Science
Colloidal
Stabilization
Drug Product
Development
Patent Application
Product
Development
Product
Ingredients
Colorant
Scale up a batch 1
Drug Delivery
Industry
Drug Delivery -
Smart Bomb
Lotion, Cream,
Preps
Enteric
Coating-Eudragit
Enteric
Coating-Nutrateric
SR
Coating-Aquacoat
Drug Industry
Drug
Competitions
Drug in
Development
Cholesterol-lowering
Drug-Terminologies
Packaging
Materials
Market
Drug Dev- 2004
Drug Dev -
2005Q1
Drug Dev- 2005Q2
Drug
Dev-2005Summer
Drug Dev-2005Q3
Orphan Drug
Protein Drug
Niche Market
Novo Norkdisk
R&D
Equipment
Blenders
CONTRACT
MANUFACT.
Nutrition
Supplements
NEW DRUGS
Arranon
Actoplus Met
Alfuzosin
Ambien CR
Avastin
Asmanex(R)
Erbitux
(cetuximab)
Gardasil
GRN163
Herceptin
Increlex (rhIGF-1)
Lidoerm
(Lidocaine)
Liraglutide
Lyrica (pregabalin)
Rozerem
Sorafenib
Sutent
Tamsulosin
Torcetrapib
Zometa
OLD DRUGS
Lithium Carbonate
DRUG NOTES
[CONSTRUCT]
Clinical Research
Terminologies
FDA ALERTS
Protein Drug
Market
Niche Market
Orphan Drug
levothyroxine
Protein Drug 1
Protein Drug2
Double-blind
Study
INDUSTRY
Foundamental
Science
Colloidal
Stabilization
Drug Product
Development
Patent Application
Product
Development
Product
Ingredients
Colorant
Scale up a batch 1
Drug Delivery
Industry
Drug Delivery -
Smart Bomb
Lotion, Cream,
Preps
Enteric
Coating-Eudragit
Enteric
Coating-Nutrateric
SR
Coating-Aquacoat
Drug Industry
Drug
Competitions
Drug in
Development
Cholesterol-lowering
Drug-Terminologies
Packaging
Materials
Market
Drug Dev- 2004
Drug Dev -
2005Q1
Drug Dev- 2005Q2
Drug
Dev-2005Summer
Drug Dev-2005Q3
Orphan Drug
Protein Drug
Niche Market
Novo Norkdisk
R&D
Equipment
Blenders
CONTRACT
MANUFACT.
Nutrition
Supplements
NEW DRUGS
Arranon
Actoplus Met
Alfuzosin
Ambien CR
Avastin
Asmanex(R)
Erbitux
(cetuximab)
Gardasil
GRN163
Herceptin
Increlex (rhIGF-1)
Lidoerm
(Lidocaine)
Liraglutide
Lyrica (pregabalin)
Rozerem
Sorafenib
Sutent
Tamsulosin
Torcetrapib
Zometa
OLD DRUGS
Lithium Carbonate
DRUG NOTES
[CONSTRUCT]
Clinical Research
Terminologies
FDA ALERTS
Protein Drug
Market
Niche Market
Orphan Drug
levothyroxine
Protein Drug 1
Protein Drug2
Double-blind
Study