855-6-RxLink	RxLink Pharmacy Business Initiative
	RxLink - Spirit of the Independent Pharmacist! Pharmacy News Drug Updates HMO News Events for Pharmacists Clinical Pharmacy Compounding Pharmacy HomeCare Pharmacy Long-Term Care  RxLink Nutrition Registration Pharmacy Staffing Pharmacy Affiliates Independent Voices E-mail us Feedback to RxLink Consulting Services Contact RxLink RxLink Archives                                           RxLink® is a Registered Trademark of RPhLink, Inc. Any unauthorized use of this Trademark would be considered the violation of law.	General Pharmacy Classified | Pharmacy Antiques | Pharmacy Collectibles | Pharmacy Archives              To: RxLink® To RxLink Pharmacy From: Pfizer 12/16/2004 We at Pfizer understand that you and your patients may have questions about arthritis medications in light of recent developments in this area. Pfizer continues to stand behind the efficacy and safety of Bextra (valdecoxib tablets) as labeled. In October 2004, we communicated important information regarding our product Bextra to the public. As we described in those communications, Pfizer and the Food and Drug Administration (FDA) have had ongoing discussions regarding Bextra product labeling. These discussions have now been finalized and have resulted in an expansion of the previous warning concerning the risk of rare but serious adverse skin reactions associated with Bextra, as well as the inclusion of a detailed description of the available cardiovascular clinical trial safety data for the product. Please take a few minutes to carefully review the important information contained in this letter regarding Bextra. Bextra is indicated for the relief of signs and symptoms of osteoarthritis and adult rheumatoid arthritis, and for the treatment of primary dysmenorrhea. As you dispense Bextra, it is important for you to know that there are new components to the Bextra product labeling, a copy of which is appended to this letter. In order of prominence, the additional information now included in the Bextra product labeling is summarized in the following section: Serious Skin Reaction: A boxed warning regarding serious skin reactions has been added to the Bextra product labeling. The previous information concerning the occurrence of serious adverse skin reactions associated with Bextra has been expanded in the WARNINGS section of the product labeling. The complete boxed warning regarding serious skin reactions is reproduced below. Serious Skin Reactions -Serious skin reactions (e.g., toxic epidermal necrolysis, Stevens-Johnson syndrome, and erythema multiforme) have been reported in patients receiving BEXTRA. Some of these reactions have resulted in death. -Patients appear to be at higher risk for these events within the first 2 weeks of treatment, but these may occur at any time during the treatment. -The reported rate of these serious skin events appears to be greater for BEXTRA as compared to other COX-2 agents. -BEXTRA should be  discontinued at the first appearance of skin rash, mucosal lesions, or any other sign of hypersensitivity. (See WARNINGS-Serious Skin Reactions) Cardiovascular Safety Information: New information regarding the available cardiovascular clinical trial safety data for Bextra (valdecoxib tablets) has been included in the CONTRAINDICATIONS, WARNINGS and CLINICAL STUDIES sections of the product labeling. Please note that Bextra is not approved for the treatment of post-operative pain in the settings described below. These labeling sections have been updated to reflect that patients treated with Bextra and parecoxib, the investigational IV prodrug of Bextra, in an investigational clinical setting evaluating these products for the treatment of pain immediately following coronary artery bypass graft (CABG) surgery, have a higher risk for cardiovascular/thromboembolic events, deep surgical infections or sternal wound complications compared to patients receiving placebo. Bextra is therefore contraindicated for the treatment of postoperative pain immediately following CABG surgery and should not be used in this setting. In general surgery study, there was no significant difference in the overall safety profile including no increased risk of CV thromboembolic events vs placebo (in both treatment arms of the study-parecoxib/valdecoxib and placebo/placebo). Data describing an analysis of the cardiovascular safety of Bextra in patients treated for OA and RA (the approved indications) are now included in the package insert. Randomized controlled clinical studies with Bextra linger than twelve months have not been conducted, nor have studies powered to detect differences in cardiovascular events in a chronic setting been conducted. A meta-analysis of 10 clinical trials suggests no apparent differences were detected in the exposure-adjusted serious cardiovascular thromboembolic event rates among patients receiving Bextra, placebo and NSAIDS. Pfizer continues to stand behind the efficacy and safety of Bextra. We are planning further studies to assess the long-term CV safety of Bextra in patients who require chronic treatment for arthritis with a COX-2 inhibitor. As a partner ion healthcare, Pfizer is also developing information specific to Bextra, reflective of the changes outlined in this letter for physicians, managed care organizations, patients, and patient advocacy groups. Our goal is to continue to help support your discussions on this important topic with your patients and with other health care professionals. Inc losing, as with all of out medications, we believe health care professionals must consider all the available information displayed in the product labeling when making treatment decisions for their patients. Pfizer is fully committed to monitoring the safety of Bextra and will continue to provide you with any important update information in order to help ensure that the product is labeled and used appropriately. We stand committed to providing you with safe and effective treatment alternatives that meet the needs of your patients. As always, if you have any questions concerning this important safety information, please contact Pfizer Inc. Medical Information at 1-800-438-1985 Sincerely, Claire Wohlhuter, MD, PhD Pain and Arthritis Medical Group Leader Pfizer, Inc. To: RxLink® To RxLink Pharmacy From: Ortho McNeil Re: Topamax                                    12-2003 Important Drug Warning The Prescribing information for Topamax (topiramate/topiramate capsules) Tablets/Sprinkle Capsules has been revised to include a warning that TOPAMAX causes hypercloremic, non-anion gap metabolic acidosis (decreased serum bicarbonate). TOPAMAX is approved and marketed for the adjunctive treatment of partial-onset seizures, generalized tonic-clonic seizures associated with the Lennox-Gastaut syndrome in adults and children two years of age and older. Data on hyperchloremic, non-anion gap metabolic acidosis are derived from placebo-controlled trials and post-marketing experience in over 2.5 million patients. In clinical trials, the rate of occurrence of a persistently decreased serum bicarbonate ranges from 23-67% for patients treated with topiramate and 1-10% for placebo. The incidence of markedly low serum bicarbonate in clinical trials ranges from 3-11% for topiramate and 1 to <1% for placebo. Generally, decreases in serum bicarbonate occur soon after initiation of topiramate, although they can occur at any time during treatment. Bicarbonate decrements are usually mild-moderate, with an average decrease of 4mEQ/L at daily doses of 400 mg in adults and approximately 6 mg/kg/day in pediatric patients. Rarely, patients can experience decrements to values below 10 mEq/L. Conditions or therapies that predispose to acidosis (such as renal disease, severe respiratory disorders, status epilepticus, diarrhea, surgery, ketogenic diet, or drugs) may be additive to the bicarbonate lowering effects of topiramate. Some manifestations of acute or chronic metabolic acidosis may include hyperventilation, nonspecific symptoms such s fatigue and anorexia, or more sever sequelae including cardiac arrhythmias or stupor. Chronic, untreated metabolic acidosis may increase the risk for nephrolithiasis or nephrocalcinosis, and may also result in osteomalacia (referred to as rickets in pediatric patients) and/or osteoporosis with an increased risk for fractures. Chronic metabolic acidosis in pediatric patients may also reduce growth rates. A reduction in growth rate may eventually decrease the maximal height achieved. The effect of topiramate on growth and bone-related sequelae has not been systematically investigated. Measurement of baseline and periodic serum bicarbonate during topiramate treatment is recommended. If metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing topiramate (using dose tapering). If the decision is made to continue patients on topiramate in the face of persistent acidosis, alkali treatment should be considered. The following has been added to TOPAMAX prescribing information. Under WARNINGS Metabolic Acidosis Hyperchloremic, non-anion gap, metabolic acidosis (i.e., decreased serum bicarbonate below the normal reference range in the absence of chronic respiratory alkalosis) is associated with topiramate treatment. This metabolic acidosis is caused by renal bicarbonate loss due to the inhibitory effect of topiramate on carbonic anhydrase. Such electrolyte imbalance has been observed with the use of topiramate in placebo-controlled clinical trials and in the post-marketing period. Generally, topiramate-induced metabolic acidosis occurs early in the treatment although cases can occur at any time during treatment. Bicarbonate decrements are usually mild-moderate (average decrease of 4mEq/L at daily doses of 400 mg in adults and at approximately 6 mg/kg/day in pediatric patients); rarely, patients can experience severe decrements to values below 10mEq/L. Conditions or therapies that predispose to acidosis (such as renal disease, severe respiratory disorders, status epilepticus, diarrhea, surgery, ketogenic diet, or drugs) may be additive to the bicarbonate lowering effects of topiramate. In adults, the incidence of persistent treatment-emergent decreases in serum bicarbonate (levels of <20 mEq/L at two consecutive visits or at the final visit) in controlled clinical trials for adjunctive treatment of epilepsy was 32% for 400 mg/day, and !% for placebo. Metabolic acidosis has been observed at doses as low as 50 mg/day. The incidence of a markedly abnormally low serum bicarbonate (i.e., absolute value <17mEq/L and >5 mEq/L decrease from pretreatment) in these trials was 3% for 400 mg/day, and 0% for placebo. Serum bicarbonate levels have not been systematically evaluated at daily doses greater than 400 mg/day. In pediatric patients (<16 years of age), the incidence of persistent treatment-emergent decreases in serum bicarbonate in placebo-controlled trials for adjunctive treatment of Lennox-Gastaut Syndrome or refractory partial onset seizures was 67% for TOPAMAX (at approximately 6 mg/kg/day), and 10% for placebo. The incidence of a markedly abnormally low serum bicarbonate (i.e., absolute value <17mEq/L and >5mEq/L decrease from pretreatment) in these trials was 11% for TOPAMAX and 0% for placebo. Cases of moderately severe metabolic acidosis have been reported in patients as young as 5 months old, especially at daily doses above 5 mg/kg/day. Although not approved for the prophylaxis of migraine, the incidence of persistent treatment-emergent decreases in serum bicarbonate in placebo-controlled trials for adults for prophylaxis of migraine was 44% for 200 mg/day, 39% for 100 mg/day, 23% for 50 mg/day, and 7% for placebo. The incidence of a markedly abnormally low serum bicarbonate (i.e., absolute value<17 mEq/L and >5mEq/L decrease from pretreatment) in these trials was 11% for 200 mg/day, 9% for 100 mg/day, 2% for 50 mg/day, and 1% for placebo. Some manifestations of acute or chronic metabolic acidosis may include hyperventilation, nonspecific symptoms such as fatigue and anorexia, or more severe sequelae including cardiac arrhythmias or stupor. Chronic, untreated metabolic acidosis may increase the risk for nephrolithiasis or nephrocalcinosis, and may also result in osteomalacia (referred to as Rickets in pediatric patients) and / or osteoporosis with an increased risk for fractures. Chronic metabolic acidosis in pediatric patients may also reduce growth rates. A reduction in growth rates may eventually decrease the maximal height achieved. The effect of topiramate on growth and bone related sequelae has not been systematically investigated. Measurement of baseline and periodic serum bicarbonate during topiramate treatment is recommended. If metabolic acidosis develops and persists, consideration should be given to reducing the dose or discontinuing topiramate (using dose tapering). If the decision is made to continue patients on topiramate in the face or persistent acidosis, alkali treatment should be considered. Under Precautions: Laboratory Tests Measurement of baseline and periodic serum bicarbonate during topiramate treatment is recommended ( see WARNINGS). Pediatric Use: Safety and effectiveness in patients below the age of 2 years have not been established. Topiramate is associated with metabolic acidosis. Chronic untreated metabolic acidosis in pediatric patients may cause osteomalacia (rickets) and may reduce growth rates. A reduction  in growth rate may eventually decrease the maximal height achieved. The effect of topiramate on growth and bone-related sequelae has not been systematically investigated (see Warnings). Under OVERDOSE: Topiramate overdose has resulted in severe metabolic acidosis (see WARNINGS). You can further our understanding of adverse events by reporting all cases to Ortho-McNeil at the contact numbers listed below or to the FDA MedWatch Program by phone (1-800 FDA 1088), by fax (1-800-FDA-0178, by mail (using postage paid form to MedWatch, FDA, 5600 Fishers Lane, Rockville, MD 20852-9787) or via www.accessdata.fda.gov/scripts//medwatch/. A copy of the full Prescribing Information is enclosed for your reference. If you have any questions regarding TOPOMAX tablets and TOPOMAX Sprinkle Caplets, please feel free to call Ortho-McNeil Medical Affairs Division at 1-800-682-6532 Sincerely, Joseph Hulihan, MD Group Director, CNS Research Ortho-McNeil Pharmaceutical, Inc. 1000 Route 202, PO Box 300 Raritan, NJ  08869-0602       908-218-6000 Telephone