Alendronate: profile and news

Cephalon Reports Outstanding Financial Results for 2005 Feb 14, 2006
The company currently markets four proprietary products in the United States: PROVIGIL, GABITRIL, ACTIQ and TRISENOX(R) (arsenic trioxide) injection, and ... - PR Newswire (press release),

Cell Therapeutics: hoping for a rich performance Feb 9, 2006
Indeed, having dispensed of Trisenox to help fund further development of Xyotax, Cell Therapeutics will be putting all of its might behind the drug and, with ... - Pharmaceutical Business Review

Early-Stage Biopharmaceuticals Firm Seeks New Funding Feb 13, 2006
FDA-approved, said Lewis. Preclinical data of the drug, Trisenox®, show significant therapeutic potential, he said. The drug has ... - American Venture Magazine,

Cephalon, Inc. Provides Update on Regulatory Status of NUVIGIL(TM) Feb 1, 2006
...products in the United States: PROVIGIL, GABITRIL(R) (tiagabine hydrochloride), ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II] and TRISENOX(R) (arsenic ... - PR Newswire (press release),

Cephalon, Inc. Provides Update on Regulatory Status of NUVIGIL(TM) Feb 1, 2006
...in the United States: PROVIGIL, GABITRIL® (tiagabine hydrochloride), ACTIQ® (oral transmucosal fentanyl citrate) [C-II] and TRISENOX® (arsenic trioxide ... - Yahoo! News (press release)

Cephalon, Inc. Announces Agreements With Barr Laboratories, Inc. ... Feb 1, 2006
...company currently markets four proprietary products in the United States: PROVIGIL, GABITRIL® (tiagabine hydrochloride), ACTIQ and TRISENOX® (arsenic trioxide ... - Yahoo! News (press release)

Cephalon, Inc. Announces Agreements With Barr Laboratories, Inc. ... Feb 1, 2006
The company currently markets four proprietary products in the United States: PROVIGIL, GABITRIL(R) (tiagabine hydrochloride), ACTIQ and TRISENOX(R) (arsenic ... - PR Newswire (press release),

Cell Therapeutics: hoping for a rich performance 09 Feb 2006
Indeed, having dispensed of Trisenox to help fund further development of Xyotax, Cell Therapeutics will be putting all of its might behind the drug and, with ... - Pharmaceutical Business Review

Cephalon, Inc. Provides Update on Regulatory Status of NUVIGIL Feb 2, 2006
...products in the United States: PROVIGIL, GABITRIL(R) (tiagabine hydrochloride), ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II] and TRISENOX(R) (arsenic ... - PharmaLive.com (press release),

Horst Witzel, Dr.-Ing., to Retire From Cephalon Board of Directors Jan 31, 2006
States: PROVIGIL(R) (modafinil) [C-IV], GABITRIL(R) (tiagabine hydrochloride), ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II] and TRISENOX(R) (arsenic ... - PR Newswire (press release),

Cephalon, Inc. Provides Update on Regulatory Status of SPARLON(TM) Jan 25, 2006
...in the United States: PROVIGIL, GABITRIL® (tiagabine hydrochloride), ACTIQ® (oral transmucosal fentanyl citrate) [C-II] and TRISENOX® (arsenic trioxide ... - Yahoo! News (press release)

Horst Witzel, Dr.-Ing., to Retire From Cephalon Board of Directors Jan 31, 2006
PROVIGIL® (modafinil) [C-IV], GABITRIL® (tiagabine hydrochloride), ACTIQ® (oral transmucosal fentanyl citrate) [C-II] and TRISENOX® (arsenic trioxide ... - Yahoo! News (press release)

Scientific Advances on Three Lead Cephalon Oncology Compounds to ... Dec 8, 2005
At ASH, researchers also will report data from investigator- sponsored studies of TRISENOX(R) (arsenic trioxide) injection, the company's marketed anti-cancer ... - PR Newswire (press release),

Scientific Advances on Three Lead Cephalon Oncology Compounds to ... Dec 8, 2005
At ASH, researchers also will report data from investigator- sponsored studies of TRISENOX® (arsenic trioxide) injection, the company's marketed anti-cancer ... - Yahoo! News (press release)

Cephalon Could Have A Tough Year In 2007 Dec 8, 2005
...deal for Cephalon, as it will provide the company with a pan-European oncology franchise to complement its existing cancer product, Trisenox, and will give the ... - Forbes

Cell Therapeutics, Inc. Reports Third Quarter 2005 Financial ... Nov 14, 2005
Total revenues for the quarter were $1.3 million, including TRISENOX(R) net sales of $1.2 million, which were recorded prior to the closing of the divestiture ... - PR Newswire (press release),

Cell Therapeutics 3Q Loss Narrows Nov 14, 2005
...on Monday reported its third-quarter loss narrowed substantially after it sold rights to its Trisenox leukemia treatment to Cephalon Inc. ... - Forbes

Women to be focus of tests on cancer drug Nov 15, 2005
...reported a smaller third-quarter loss Monday mainly because it booked $30.5 million in one-time revenue from the sale of its leukemia drug Trisenox to Cephalon ... - Seattle Times,

Cephalon, Inc. Announces Agreement to Acquire Zeneus Holdings ... Dec 5, 2005
States: PROVIGIL(R) (modafinil) [C-IV], GABITRIL(R) (tiagabine hydrochloride), ACTIQ(R) (oral transmucosal fentanyl citrate) [C-II] and TRISENOX(R) (arsenic ... - PR Newswire UK (press release),

Cephalon expected to buy British drugmaker Dec 6, 2005
...$160 million. In June, Cephalon bought a marketed oncology product, Trisenox, from Cell Therapeutics Inc., Seattle. The acquisition ... - philly.com,

Cell Therapeutics cites loss Nov 14, 2005
...share. CTI attributed the decrease largely to the approximately $68 million sale of Trisenox, its only government-approved drug. ... - Seattle Post Intelligencer

TABLE-Cell Therapeutics Q3 net loss narrows Nov 14, 2005
...--Cell Therapeutics said the net loss for the latest third quarter was after giving effect to a gain of $30.5 million on TRISENOX divestiture. ... - Reuters

Source: Cephalon, Inc.; Zeneus Holdings Limited Dec 5, 2005
PROVIGIL® (modafinil) [C-IV], GABITRIL® (tiagabine hydrochloride), ACTIQ® (oral transmucosal fentanyl citrate) [C-II] and TRISENOX® (arsenic trioxide ... - Yahoo! News (press release)

BMS' dasatinib expected to rival Gleevec Nov 21, 2005
...said, they will likely have a negative impact on the development of other CML medications, such as ChemGenex's Ceflatonin and Cell Therapeutics' Trisenox. ... - Science Daily (press release)

Shedding workers Sep 26, 2005
...past year, including disappointing late-stage clinical trials for its Xyotax anti-cancer treatment and the sale of its only federally approved drug, Trisenox. ... - MSNBC

FDA Extends PDUFA Date for VIVITREX(R) to December 30, 2005 ... Sep 20, 2005
States: PROVIGIL(R) (modafinil) (C-IV), GABITRIL(R) (tiagabine hydrochloride), ACTIQ(R) (oral transmucosal fentanyl citrate) (C-II) and TRISENOX(R) (arsenic ... - Genetic Engineering News,

Cephalon Receives FDA Approval to Market Sugar-Free Formulation of ... Sep 12, 2005
...markets four proprietary products in the United States: PROVIGIL(R) (modafinil) [C-IV], GABITRIL(R) (tiagabine hydrochloride), ACTIQ, and TRISENOX(R) (arsenic ... - PharmaLive.com (press release),

Cephalon Receives FDA Approval to Market Sugar-Free Formulation of ... Sep 12, 2005
...four proprietary products in the United States: PROVIGIL® (modafinil) [C-IV], GABITRIL® (tiagabine hydrochloride), ACTIQ, and TRISENOX® (arsenic trioxide ... - Yahoo! News (press release)

Other information

Indication
For the treatment and prevention of osteoporosis in women and Paget's disease of bone in both men and women

Pharmacology
Alendronate, a second-generation bisphosphonate is the first member of a group of drugs which strengthens bone. Alendronate is used to reduce hypercalcemia in tumor-induced bone disease, to treat corticosteroid-induced osteoporosis and Paget's disease, and to prevent osteoporosis in postmenopausal women.

Mechanism Of Action
The action of Alendronate on bone tissue is based partly on its affinity for hydroxyapatite, which is part of the mineral matrix of bone. Alendronate also targets farnesyl pyrophosphate (FPP) synthase. Nitrogen-containing bisphosphonates (such as pamidronate, alendronate, risedronate, ibandronate and zoledronate) appear to act as analogues of isoprenoid diphosphate lipids, thereby inhibiting FPP synthase, an enzyme in the mevalonate pathway. Inhibition of this enzyme in osteoclasts prevents the biosynthesis of isoprenoid lipids (FPP and GGPP) that are essential for the post-translational farnesylation and geranylgeranylation of small GTPase signalling proteins. This activity inhibits osteoclast activity and reduces bone resorption and turnover. In postmenopausal women, it reduces the elevated rate of bone turnover, leading to, on average, a net gain in bone mass.

Drug Category
Antiresorptives; Bisphosphonates; Antihypocalcemic Agents; ATC:M05BA04

Brand Names/Synonyms
ALENDRONIC ACID; Acide Alendronique [Inn-French]; Acido Alendronico [Inn-Spanish]; Acidum Alendronicum [Inn-Latin]; Adronat; Alendronate; Alendronate Sodium; Alendronic Acid; Alendronic Acid [Ban:Inn]; Alendros; Arendal; CHEMBANK1709; Fosamax; MK 217; Onclast

Dosage Forms
10 mg (Rx) Fosamax lactose 40 mg (Rx) Fosamax lactose

Absorption
Relative to an intravenous (IV) reference dose, the mean oral bioavailability of alendronate in women was 0.7% for doses ranging from 5 to 40 mg when administered after an overnight fast and two hours before a standardized breakfast. Oral bioavailability of the 10 mg tablet in men (0.59%) was similar to that in women (0.78%) when administered after an overnight fast and 2 hours before breakfast.

Interactions
Intravenous ranitidine was shown to double the bioavailability of oral alendronate. The clinical significance of this increased bioavailability and whether similar increases will occur in patients given oral H2-antagonists is unknown; no other specific drug interaction studies were performed. Products containing calcium and other multivalent cations likely will interfere with absorption of alendronate.

Chemical IUPAC Name
(4-amino-1-hydroxy-1-phosphono-butyl)phosphonic acid

Chemical Formula
C4H13NO7P2

Half Life
>10 years

Drug Type
Approved Drug

# Accession No
APRD00561

CAS Registry Number
66376-36-1