Bextra: profile and news

Sane steps may save your precious central vision  07 Mar 2006
Visudyne by QLT and Novartis and Macugen by Eyetech Pharmaceuticals and Pfizer have also been shown to slow deterioration of eyesight in wet type degeneration. ... - Roanoke Times,

Stocks: Ann Taylor fashions sales gains  07 Mar 2006
But Genentech Inc.’s Lucentis drug -- potentially a major rival to OSI’s age-related blindness treatment Macugen -- is undergoing a priority review by ... - Crain's New York Business,

OSI gains on upgrade  07 Mar 2006
Lucentis would compete with OSI’s Macugen, which also fights neovascular age-related macular degeneration, a cause of blindness in the elderly. - Long Island Business News (subscription),

Systemic Safety Profile of Macugen(R) (pegaptanib sodium injection ...  Feb 24, 2006
OSI Pharmaceuticals, Inc. (NASDAQ: OSIP) and Pfizer Inc (NYSE: PFE) announced today that the systemic safety profile of Macugen(R) (pegaptanib sodium injection ... - Genetic Engineering News,

Pfizer's Macugen Demonstrates Prolonged Safety Profile  Feb 20, 2006
In a two-year review of safety data from a trial evaluating Pfizer's wet AMD medication Macugen, the VEGF inhibitor was not associated with an increased risk ... - International News Service,

Pfizer's Macugen approved in Europe  Feb 3, 2006
The European Commission has granted marketing approval for Pfizer's eye drug, Macugen, for the treatment of wet age related macular degeneration, a disease ... - Pharmaceutical Business Review

Macugen drug for treating degenerative eye disease  Feb 5, 2006
The drug Macugen is found to be effective in treating wet age related macular degeneration disease which is a progressive disease of the macula. ... - MedIndia,

International Approvals: Tamiflu, Macugen, Naglazyme  Feb 13, 2006
On February 2, the European Commission approved pegaptanib sodium injection (Macugen, made by OSI Pharmaceuticals, Inc, and marketed by Pfizer, Inc) for the ... - Medscape (subscription)

Pfizer's Macugen cleared for marketing in EU  Feb 3, 2006
The European Commission has approved Pfizer's Macugen product for the treatment of neovascular age-related macular degeneration, an eye disease that destroys ... - Pharma Times (subscription),

Pfizer, OSI get Macugen OK in Europe  Feb 2, 2006
...and partner OSI Pharmaceuticals Inc. said Thursday that their age-related blindness treatment Macugen received marketing approval in Europe. ... - BusinessWeek

OSI Pharmaceuticals Announces European Regulatory Approval for ...  Feb 2, 2006
...(NASDAQ: OSIP) said today that the European Commission has granted its development and marketing partner, Pfizer Inc, approval to market Macugen(R) (pegaptanib ... - Genetic Engineering News,

European Commission Approves Macugen for Treatment of All Types of ...  Feb 2, 2006
2 /PRNewswire-FirstCall/ -- Pfizer Inc said today that the European Commission has granted marketing authorization for Macugen(R) (pegaptanib sodium injection ... - PR Newswire (press release),

European Commission Approves Macugen for Treatment of All Types of ...  Feb 2, 2006
February 02, 2006 /PRNewswire-FirstCall/ -- Pfizer Inc said today that the European Commission has granted marketing authorization for Macugen(R) (pegaptanib ... - PharmaLive.com (press release),

Pfizer, OSI Get Macugen OK in Europe  Feb 2, 2006
...and partner OSI Pharmaceuticals Inc. said Thursday that their age-related blindness treatment Macugen received marketing approval in Europe. ... - Houston Chronicle,

UPDATE 2-Genentech gets FDA priority review for eye drug  Feb 28, 2006
...(OSIP.O: Quote, Profile, Research), whose drug Macugen will compete directly with Lucentis. The Genentech drug is considered to ... - Reuters

UPDATE 1-Novartis files Genentech's Lucentis for EU approval  Mar 1, 2006
Lucentis will compete directly with Macugen, a medicine made by OSI Pharmaceuticals Inc. (OSIP.O: Quote, Profile, Research). The ... - Reuters

OSI injection safe over two years  Feb 24, 2006
OSI said Macugen's systemic safety profile, established in the first year of the study, was maintained over two years of treatment, with no evidence of an ... - BusinessWeek

SunTrust Boosts OSI Pharma To Buy From Neutral  Feb 23, 2006
The analyst said "the negative sentiment towards the acquisition has run its course and investors have begun to refocus on Tarceva and Macugen sales.". ... - New Ratings

Inflation Fears Linger  Mar 3, 2006
It also updated its 2005 net revenue for Macugen, a drug for neovascular age-related macular degeneration, to be between $183 million and $185 million from the ... - Trading Markets,

OSI Pharmaceuticals to Present at the Cowen & Co. Healthcare ...  Mar 2, 2006
Macugen(R) (pegaptanib sodium injection) is approved in the United States for the treatment of neovascular age-related macular degeneration. ... - Genetic Engineering News,

Enzon to Present at Cowen 26th Annual Health Care Conference  Mar 3, 2006
In addition, Enzon alsoreceives royalties on sales of PEG-INTRON(R), marketed bySchering-Plough Corporation, and MACUGEN(R), marketed by OSIPharmaceuticals and ... - Finanzen.net,

A review of developments in the management of retinal diseases  Feb 28, 2006
Macugen is a highly selective inhibitor of vascular endothelial growth factor with anti-angiogenic and anti-permeability effects. ... - Journal of the Royal Society of Medicine

OSI drug passes two-year trial  Feb 24, 2006
According to OSI, based in Melville, the macular degeneration drug Macugen demonstrated prolonged safety and didn’t bring about blood clotting, excessive ... - Long Island Business News (subscription),

Enzon to Present at Cowen 26th Annual Health Care Conference  Mar 3, 2006
In addition, Enzon also receives royalties on sales of PEG-INTRON(R), marketed by Schering-Plough Corporation, and MACUGEN(R), marketed by OSI Pharmaceuticals ... - PharmaLive.com (press release),

National business briefs  Feb 3, 2006
The drug, Macugen, which is already approved in the US, targets the "wet" form of the disease, which is caused by damage to the retina from leaking blood ... - NorthJersey.com,

Genentech gets Lucentis priority review  Mar 1, 2006
...$85.69. The leading FDA approved drug for the condition, Macugen, is owned by OSI Pharmaceuticals Inc. and marketed by Pfizer Inc. ... - BusinessWeek

Eye disease attacking boomers  Mar 3, 2006
Several drugs, Visudyne by QLT and Novartis and Macugen by Eyetech Pharmaceuticals and Pfizer, have also been shown to slow deterioration. - Toronto Star,

OSI will ask for input  Feb 7, 2006
...written notice. OSI recently acquired Manhattan-based Eyetech Pharmaceuticals, the maker of Macugen, a vision-loss drug. The deal ... - Newsday,

OSI gets EU OK on eye drug  Feb 2, 2006
MELVILLE, NY, Feb. 2 (UPI) -- OSI Pharmaceuticals said Thursday it got European OK to sell its injectable Macugen to treat macular degeneration. ... - United Press International

IN BRIEF  Feb 3, 2006
...and partner OSI Pharmaceuticals Inc. said yesterday that their age-related blindness treatment Macugen received marketing approval in Europe. ... - Newsday,

Regeneron Reports Fourth Quarter and Full Year 2005 Financial and ...  Feb 24, 2006
...has already initiated a part B of the phase 1 trial, which is comparing a single intravitreal injection of the VEGF Trap - Eye with Macugen(R) (pegaptanib ... - Genetic Engineering News,

Pfizer macular degeneration drug wins European OK  Feb 2, 2006
NEW YORK, Feb 2 (Reuters) - Pfizer Inc. (PFE.N: Quote, Profile, Research) on Thursday said the European Commission has approved its drug Macugen as a treatment ... - Reuters

Try reducing the chance of macular degeneration  Feb 7, 2006
...permanently. A treatment called Macugen stops new blood vessels from bleeding. It requires an injection into the eye every six weeks. ... - Indianapolis Star,

Pfizer Driving Performance Through Growth of Current and New ...  Feb 10, 2006
R&D activities, Dr. LaMattina said the company has established a firm foothold in biologics with medicines including Genotropin and Macugen, among others. ... - MSN Money

Intensifying research to fight diseases  Feb 3, 2006
Lyrica) for neuropathic pain and as an adjunctive therapy for partial epileptic seizures, indiplon for insomnia, pegaptanib sodium injection (Macugen) for age ... - INQ7.net,

Clarus Ventures Expands Investment Team  Feb 9, 2006
At Eyetech, Dr. Cunningham played a leadership role in the development and approval of Macugen for age-related macular degeneration. ... - PR Newswire (press release),

(PRN) - Kellogg Company's Smart Start Healthy Heart Brand Launches ...  Feb 2, 2006
...[+]. (PRN) - Sun Announces Release of Open Source NetBeans 5 IDE ... [+. PRN) - European Commission Approves Macugen for Treatment of All Types of Wet Age ... - Bolsamania.com,

The drug interaction studies with valdecoxib were performed both with valdecoxib and a rapidly hydrolyzed intravenous prodrug form. The results from trials using the intravenous prodrug are reported in this section as they relate to the role of valdecoxib in drug interactions.

General: In humans, valdecoxib metabolism is predominantly mediated via CYP 3A4 and 2C9 with glucuronidation being a further (20%) route of metabolism. In vitro studies indicate that valdecoxib is a moderate inhibitor of CYP 2C19 (IC50 = 6 µg/mL or 19 µM) and 2C9 (IC50 = 13 µg/mL or 41 µM), and a weak inhibitor of CYP 2D6 (IC50 = 31 µg/mL or 100 µM) and 3A4 (IC50 = 44 µg/mL or 141 µM )..

Aspirin: Concomitant administration of aspirin with valdecoxib may result in an increased risk of GI ulceration and complications compared to valdecoxib alone. Because of its lack of anti-platelet effect valdecoxib is not a substitute for aspirin for cardiovascular prophylaxis. In a parallel group drug interaction study comparing the intravenous prodrug form of valdecoxib at 40 mg BID (n=10) vs placebo (n=9), valdecoxib had no effect on in vitro aspirin-mediated inhibition of arachidonate- or collagen-stimulated platelet aggregation.

Methotrexate: Valdecoxib 10 mg BID did not show a significant effect on the plasma exposure or renal clearance of methotrexate.

ACE-inhibitors:Reports suggest that NSAIDs may diminish the antihypertensive effect of ACE-inhibitors. This interaction should be given consideration in patients taking BEXTRA concomitantly with ACE-inhibitors.

Furosemide: Clinical studies, as well as post-marketing observations, have shown that NSAIDs can reduce the natriuretic effect of furosemide and thiazides in some patients. This response has been attributed to inhibition of renal prostaglandin synthesis.

Anticonvulsants (Phenytoin): Steady state plasma exposure (AUC) of valdecoxib (40 mg BID for 12 days) was decreased by 27% when co-administered with multiple doses (300 mg QD for 12 days) of phenytoin (a CYP 3A4 inducer). Patients already stabilized on valdecoxib should be closely monitored for loss of symptom control with phenytoin coadministration. Valdecoxib did not have a statistically significant effect on the pharmacokinetics of phenytoin (a CYP 2C9 and CYP 2C19 substrate).

Drug interaction studies with other anticonvulsants have not been conducted. Routine monitoring should be performed when therapy with BEXTRA is either initiated or discontinued in patients on anticonvulsant therapy.

Dextromethorphan: Dextromethorphan is primarily metabolized by CYP 2D6 and to a lesser extent by 3A4. Coadministration with valdecoxib (40 mg BID for 7 days) resulted in a significant increase in dextromethorphan plasma levels suggesting that, at these doses, valdecoxib is a weak inhibitor of 2D6. Even so dextromethorphan plasma concentrations in the presence of high doses of valdecoxib were almost 5-fold lower than those seen in CYP 2D6 poor metabolizers suggesting that dose adjustment is not necessary.

Lithium: Valdecoxib 40 mg BID for 7 days produced significant decreases in lithium serum clearance (25%) and renal clearance (30%) with a 34% higher serum exposure compared to lithium alone. Lithium serum concentrations should be monitored closely when initiating or changing therapy with BEXTRA in patients receiving lithium. Lithium carbonate (450 mg BID for 7 days) had no effect on valdecoxib pharmacokinetics.

Warfarin: The effect of valdecoxib on the anticoagulant effect of warfarin (1 - 8 mg/day) was studied in healthy subjects by coadministration of BEXTRA 40 mg BID for 7 days. Valdecoxib caused a statistically significant increase in plasma exposures of R-warfarin and S-warfarin (12% and 15%, respectively), and in the pharmacodynamic effects (prothrombin time, measured as INR) of warfarin. While mean INR values were only slightly increased with coadministration of valdecoxib, the day-to-day variability in individual INR values was increased. Anticoagulant therapy should be monitored, particularly during the first few weeks, after initiating therapy with BEXTRA in patients receiving warfarin or similar agents.

Fluconazole and Ketoconazole: Ketoconazole and fluconazole are predominantly CYP 3A4 and 2C9 inhibitors, respectively. Concomitant single dose administration of valdecoxib 20 mg with multiple doses of ketoconazole and fluconazole produced a significant increase in exposure of valdecoxib. Plasma exposure (AUC) to valdecoxib was increased 62% when coadministered with fluconazole and 38% when coadministered with ketoconazole.

Glyburide: Glyburide is a CYP 2C9 substrate. Coadministration of valdecoxib (10 mg BID for 7 days) with glyburide (5 mg QD or 10 mg BID) did not affect the pharmacokinetics (exposure) of glyburide. Coadministration of valdecoxib (40 mg BID (day 1) and 40 mg QD (days 2-7)) with glyburide (5 mg QD) did not affect either the pharmacokinetics (exposure) or the pharmacodynamics (blood glucose and insulin levels) of glyburide. Coadministration of valdecoxib (40 mg BID (day 1) and 40 mg QD (days 2-7)) with glyburide (10 mg glyburide BID) resulted in 21% increase in glyburide AUC_0-12 and a 16% increase in glyburide C_max leading to a 16% decrease in glucose AUC_0-24. Insulin parameters were not affected.

Because changes in glucose concentrations with valdecoxib coadministration were within the normal variability and individual glucose concentrations were above or near 70 mg/dL, dose adjustment for glyburide (5 mg QD and 10 mg BID) with valdecoxib coadministration (up to 40 mg QD) is not indicated. Coadministration of glyburide with doses higher than 40 mg valdecoxib (e.g., 40 mg BID) have not been studied.

Omeprazole: Omeprazole is a CYP 3A4 substrate and CYP 2C19 substrate and inhibitor. Valdecoxib steady state plasma concentrations (40 mg BID) were not affected significantly with multiple doses of omeprazole (40 mg QD). Coadministration with valdecoxib increased exposure of omeprazole (AUC) by 46%. Drugs whose absorption is sensitive to pH may be negatively impacted by concomitant administration of omeprazole and valdecoxib. However, because higher doses (up to 360 mg QD) of omeprazole are tolerated in Zollinger-Ellison (ZE) patients, no dose adjustment for omeprazole is recommended at current doses. Coadministration of valdecoxib with doses higher than 40 mg QD omeprazole has not been studied.

Oral Contraceptives: Valdecoxib (40 mg BID) did not induce the metabolism of the combination oral contraceptive norethindrone/ethinyl estradiol (1 mg /35 mcg combination, Ortho-Novum 1/35^®). Coadministration of valdecoxib and Ortho-Novum 1/35^® increased the exposure of norethindrone and ethinyl estradiol by 20% and 34%, respectively. Although there is little risk for loss of contraceptive efficacy, the clinical significance of these increased exposures in terms of safety is not known. These increased exposures of norethindrone and ethinyl estradiol should be taken into consideration when selecting an oral contraceptive for women taking valdecoxib.

Diazepam: Diazepam (Valium) is a CYP 3A4 and CYP 2C19 substrate. Plasma exposure of diazepam (10 mg BID) was increased by 28% following administration of valdecoxib (40 mg BID) for 12 days, while plasma exposure of valdecoxib (40 mg BID) was not substantially increased following administration of diazepam (10 mg BID) for 12 days.

Although the magnitude of changes in diazepam plasma exposure when coadministered with valdecoxib were not sufficient to warrant dosage adjustments, patients may experience enhanced sedative side effects caused by increased exposure of diazepam under this circumstance. Patients should be cautioned against engaging in hazardous activities requiring complete mental alertness such as operating machinery or driving a motor vehicle.