DOCSLIB.ORG

New Restrictions on Celecoxib (Celebrex) Use and the Withdrawal of Valdecoxib (Bextra)

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text

Load more

Early release, published at www.cmaj.ca on April 15, 2005. Subject to revision. HEALTH AND DRUG ALERTS P RACTICE New restrictions on celecoxib (Celebrex) use and the withdrawal of valdecoxib (Bextra) Early release, published at www.cmaj.ca on Apr. 15, 2005. Subject to revision. Reason for posting: Coxibs, v. 0.5%; risk ratio 3.7, 95% CI the class of NSAIDs that selec- 1.0–13.5).2 Amid concerns about Table 1: The degree of inhibition of COX-2 relative tively inhibit cyclooxygenase 2 reports of severe cutaneous reac- to COX-1 for various NSAIDs (COX-2), were designed to re- tions (Stevens–Johnson syn- NSAID type COX-2 selectivity* duce joint pain and inflamma- drome, erythema multiforme, tion without causing the gastric toxic epidermal necrolysis) COX-2 selective inhibitors epithelial adverse effects typical among patients taking valde- Rofecoxib 80 of nonselective NSAIDs. Rofe- coxib,5 the drug was removed Etodolac 23 coxib (Vioxx) was withdrawn from the market. Meloxicam 11 from the market in September Celecoxib 9 2004 over concerns about car- What to do: COX-2 inhibitors Nonselective NSAIDs diovascular adverse effects, and appear to increase the risk of car- Diclofenac 4 key safety trials involving cele- diovascular adverse events in a Sulindac 3 coxib (Celebrex)1 and valdecoxib dose-related fashion, and all pa- Piroxicam 2 (Bextra)2 have recently been tients should be informed of this. Ibuprofen 0.4 published. Health Canada now Calculating the patient’s baseline Naproxen 0.3 recommends new restrictions on risk of cardiovascular disease Indomethacin 0.2 celecoxib use, and valdecoxib (e.g., with Framingham risk cal- Ketorolac 0.003 has been taken off the market.3 culators) may be wise, and cele- Note: COX = cyclooxygenase. The US Food and Drug Ad- coxib should not be prescribed to *The 80% inhibitory concentration ratios of COX-2 relative to COX-1 in ministration has gone further, patients with cardiovascular dis- human whole blood assays.6 directing that all prescription ease or diabetes or those at in- and over-the-counter NSAIDs creased risk of cardiovascular include specific information re- events. Celecoxib should be used References 1. Solomon SD, McMurray JJ, Pfeffer garding potential cardiovascular, in the lowest effective doses for MA, Wittes J, Fowler R, Finn P, et al. gastrointestinal and other risks.4 short periods (weeks) only. A Cardiovascular risk associated with risk–benefit discussion is neces- celecoxib in a clinical trial for col- orectal adenoma prevention. N Engl J The drugs: The results of re- sary for those requiring the drug Med 2005;352:1071-80. cent trials have raised concerns for a longer period. Of note, pa- 2. Nussmeier NA, Whelton AA, Brown 1 MT, Langford RM, Hoeft A, Parlow that coxib use increases the risk tients in the APC study who JL, et al. Complications of the Cox-2 of cardiovascular adverse events. used celecoxib for 3 years at a inhibitors parecoxib and valdecoxib In the APC study, a trial on col- dose double that recommended after cardiac surgery. N Engl J Med 2005;352:1081-91. orectal adenoma prevention, for osteoarthritis had an increase 3. Health Canada. Advisory: Health 2035 patients were randomly as- in absolute risk of cardiovascular Canada has asked Pfizer to suspend signed to celecoxib 200 mg events of about 1.3% (number sales of its drug Bextra and informs Canadians of new restrictions on the twice daily or 400 mg twice needed to harm of 77). use of Celebrex. 07 Apr 2005. Available daily or placebo. After about 3 The only NSAID known to at: www.hc-sc.gc.ca/english/protection /warnings/2005/2005_17.html (ac- years, cardiovascular events reduce primary and secondary cessed 2005 Apr 12). (death from cardiovascular cardiovascular events is ASA. The 4. US Food and Drug Administration. causes, myocardial infarction, absolute risk of other NSAIDs is FDA Public Health Advisory: FDA an- nounces important changes and addi- stroke, heart failure) had oc- unclear. Appreciating the relative tional warnings for COX-2 selective curred in 1% of patients receiv- degree of COX-2 selectivity of and non-selective non-steroidal anti-in- ing placebo, 2.3% of the group some commonly used NSAIDs flammatory drugs (NSAIDs). Available at: www.fda.gov/cder/drug/advisory taking 200 mg celecoxib (hazard (Table 1) may be useful. Alterna- /COX2.htm (accessed 2005 Apr 13). ratio [HR] 2.3, 95% confidence tive pharmacologic and nonphar- 5. Health Canada. Health Canada en- dorsed important safety information interval [CI] 0.9–5.5), and 3.4% macologic approaches to pain on BEXTRA (valdecoxib) tablets [let- (HR 3.4, 95% CI 1.4–7.8) of the management should be reviewed ter]. Dec. 10, 2004. Available at: group taking 400 mg.1 and strongly considered. www.hc-sc.gc.ca/hpfb-dgpsa/tpd-dpt /bextra2_hpc_e.html (accessed 2005 In a trial involving 1671 pa- Apr 14). tients who underwent coronary 6. Warner TD, Giuliano F, Vojnovic I, Jill Cotter artery bypass grafting, cardiovas- Bukasa A, Mitchell JA, Vane JR. Resident Nonsteroid drug selectivities for cy- cular events were more frequent Department of Family Medicine clo-oxygenase-1 rather than cyclo- among those taking valdecoxib University of Ottawa oxygenase-2 are associated with hu- man gastrointestinal toxicity: a full and parecoxib for pain than Eric Wooltorton in-vitro analysis. Proc Natl Acad Sci DOI:10.1503/cmaj.050456 among those taking placebo (2% CMAJ USA 1999;96:7563-8. CMAJ • MAY 10, 2005; 172 (10) 1299 © 2005 CMA Media Inc. or its licensors.
Recommended publications
  • Emerging Drug List PARECOXIB SODIUM

    Emerging Drug List PARECOXIB SODIUM

    Emerging Drug List PARECOXIB SODIUM NO. 10 MAY 2001 Generic (Trade Name): Parecoxib sodium Manufacturer: Pharmacia & Upjohn Inc. Indication: For peri-operative pain relief Current Regulatory Parecoxib is currently under review at Health Canada and the Food and Drug Status: Administration in the U.S. They are expecting approval in the fourth quarter of 2001. It is not marketed in any country at this time Description: Parecoxib is the first parenteral cyclooxygenase-2 (COX-2) selective inhibitor to be developed. It is a water-soluble prodrug that is rapidly hydrolyzed to valdecoxib (the active COX-2 inhibitor). Valdecoxib's affinity for COX-2 versus COX-1 is 90 times greater than celecoxib and 34,000 times greater than ketorolac. Once injected, peak concentrations of valdecoxib are attained in 10 to 20 minutes. Valdecoxib has a half-life of eight to 10 hours. Current Treatment: Currently, the only other nonsteroidal anti-inflammatory agent that is available as an injection is ketorolac. Ketorolac is used in some centres for peri-operative pain management, however opioids are the main class of agents used for this indication. Ketorolac has been associated with a relatively high incidence of gastrointestinal (GI) side effects, including severe cases of hemorrhage. Cost: There is no information available on the cost of parecoxib. Evidence: Parecoxib has been compared to ketorolac and morphine in clinical trials. Parecoxib at a dose of 20 and 40 mg/day IV, were compared to ketorolac, 30 mg/day IV and morphine, 4 mg/day or placebo in 202 women undergoing hysterectomy. Both doses of parecoxib were comparable to ketorolac for relieving postoperative pain.
  • Efficacy and Safety of Celecoxib

    Efficacy and Safety of Celecoxib

    ORIGINAL PAPER Nagoya J. Med. Sci. 77. 81 ~ 93, 2015 EFFICACY AND SAFETY OF CELECOXIB COMPARED WITH PLACEBO AND ETODOLAC FOR ACUTE POSTOPERATIVE PAIN: A MULTICENTER, DOUBLE-BLIND, RANDOMIZED, PARALLEL-GROUP, CONTROLLED TRIAL NAOKI ISHIGURO1, MD, PhD; AKIO HANAOKA2, MS; TOSHIYUKI OKADA2, MS; and MASANORI ITO3, PhD 1Department of Orthopedic Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan 2Clinical Development 1, Astellas Pharma Inc., Tokyo, Japan 3Global Data Science, Astellas Pharma Global Development Inc., Northbrook, IL, US ABSTRACT Celecoxib is a nonsteroidal anti-inflammatory drug (selective cyclooxygenase-2 inhibitor) that is widely used. The efficacy and safety of celecoxib for treatment of acute postoperative pain were evaluated in Japanese patients. The objective was to assess whether celecoxib showed superiority over placebo treatment and non-inferiority versus etodolac (another selective cyclooxygenase-2 inhibitor) that has been widely used for the management of acute pain. A multicenter, double-blind, randomized, parallel-group, controlled study was performed, in which 616 patients with postoperative pain received celecoxib, etodolac, or placebo. Their impressions of study drug efficacy (overall assessment) and pain intensity were evaluated. Based on each patient’s overall assessment of pain, the efficacy rate was 63.7% in the placebo group, 76.2% in the celecoxib group, and 68.0% in the etodolac group, with these results demonstrating superiority of celecoxib to placebo and noninferiority versus etodolac. The efficacy rate was significantly higher in the celecoxib group than in the etodolac group. There were no adverse events specific to celecoxib, and the safety of celecoxib was similar to that of placebo. Celecoxib was superior to etodolac for controlling acute postoperative pain.
  • Development and Validation of an Ultra Performance Liquid

    Development and Validation of an Ultra Performance Liquid

    DOI: 10.4274/tjps.76588 Turk J Pharm Sci 2017;14(1):1-8 ORIGINAL ARTICLE Development and Validation of an Ultra Performance Liquid Chromatography Method for the Determination of Dexketoprofen Trometamol, Salicylic Acid and Diclofenac Sodium Deksketoprofen Trometamol, Salisilik Asit ve Diklofenak Sodyum Etkin Maddeleri için Ultra Performanslı Sıvı Kromatografisi Yönteminin Geliştirilmesi ve Validasyonu Sibel İLBASMIŞ TAMER Gazi University, Faculty of Pharmacy, Department of Pharmaceutical Technology, Ankara, Turkey ABSTRACT Objectives: A simple, fast, accurate and precise method has been developed for the determination of dexketoprofen trometamol (DKP), salicylic acid (SA) and diclofenac sodium (DIC) in the drug solutions using ultra high performance liquid chromatography (UPLC). Materials and Methods: UPLC method is highly reliable and sensitive method to quantify the amount of the active ingredient and the method is validated according to ICH guidelines. Results: The developed method is found to be precise, accurate, specific and selective. The method was also found to be linear and reproducible. The value of limit of dedection (LOD) of DKP, SA, DIC were found 0.00325 µg/mL, 0.0027 µg/mL and 0.0304 µg/mL, respectively. The limit of quantitation (LOQ) of DKP, SA and DIC were found 0.00985 µg/mL, 0.0081 µg/mL and 0.0920 µg/mL, respectively. Conclusion: Proposed methods can be successfully applicable to the pharmaceutical preparation containing the above mentioned drugs (dexketoprofen trometamol, salicylic acid and diclofenac sodium). Even very small amounts of active substance can be analyzed and validations can be performed easily. Key words: Dexketoprofen trometamol, salicylic acid, diclofenac sodium, UPLC, validation ÖZ Amaç: Deksketoprofen trometamol (DKP), salisilik asit (SA) ve diklofenak sodyumun (DIC) ilaç çözeltisindeki analizi için ultra yüksek basınçlı sıvı kromatografisi (UPLC) kullanılarak basit, hızlı, doğru ve kesin bir yöntem geliştirilmiştir.
  • (Ketorolac Tromethamine Tablets) Rx Only WARNING TORADOL

    (Ketorolac Tromethamine Tablets) Rx Only WARNING TORADOL

    TORADOL ORAL (ketorolac tromethamine tablets) Rx only WARNING TORADOLORAL (ketorolac tromethamine), a nonsteroidal anti-inflammatory drug (NSAID), is indicated for the short-term (up to 5 days in adults), management of moderately severe acute pain that requires analgesia at the opioid level and only as continuation treatment following IV or IM dosing of ketorolac tromethamine, if necessary. The total combined duration of use of TORADOLORAL and ketorolac tromethamine should not exceed 5 days. TORADOLORAL is not indicated for use in pediatric patients and it is NOT indicated for minor or chronic painful conditions. Increasing the dose of TORADOLORAL beyond a daily maximum of 40 mg in adults will not provide better efficacy but will increase the risk of developing serious adverse events. GASTROINTESTINAL RISK Ketorolac tromethamine, including TORADOL can cause peptic ulcers, gastrointestinal bleeding and/or perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Therefore, TORADOL is CONTRAINDICATED in patients with active peptic ulcer disease, in patients with recent gastrointestinal bleeding or perforation, and in patients with a history of peptic ulcer disease or gastrointestinal bleeding. Elderly patients are at greater risk for serious gastrointestinal events (see WARNINGS). CARDIOVASCULAR RISK NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk (see WARNINGS and CLINICAL STUDIES). TORADOL is CONTRAINDICATED for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).
  • Celecoxib but Not Rofecoxib Inhibits the Growth of Transformed Cells in Vitro

    Celecoxib but Not Rofecoxib Inhibits the Growth of Transformed Cells in Vitro

    Vol. 10, 267–271, January 1, 2004 Clinical Cancer Research 267 Celecoxib But Not Rofecoxib Inhibits the Growth of Transformed Cells in Vitro Diana Kazanov,1 Hadas Dvory-Sobol,1,3 Conclusions: Celecoxib may prove to be a very efficient Marjorie Pick,2 Eliezer Liberman,1,3 component in the prevention and treatment of gastrointes- Ludmila Strier,1 Efrat Choen-Noyman,1,3 tinal tumors because it inhibits the growth of cancerous cells without affecting the growth of normal cells. Varda Deutsch,2,3 Talya Kunik,1 and Nadir Arber1,3 Departments of 1Cancer Prevention and 2Hematology, Tel Aviv INTRODUCTION Medical Center, and 3Sackler Faculty of Medicine, Tel Aviv Colorectal cancer (CRC), with an estimated lifetime risk of University, Tel Aviv, Israel 5–6%, is a major health concern in the Western world (1, 2). The goal of achieving effective cancer prevention is driven by ABSTRACT the prediction that cancer will become the leading cause of death (surpassing heart disease) during this decade, with an estimated Purpose: Nonsteroidal anti-inflammatory drugs reduce 1,000,000 new cases and Ͼ500,000 deaths/year, worldwide the risk of colorectal cancer. The cyclooxygenase (COX) (1–3). Despite continuing advances in diagnosis and therapy, pathway of arachidonic acid metabolism is an important long-term survival has not improved significantly over the last target for nonsteroidal anti-inflammatory drugs. Increased four decades. Nearly 50% of all CRC patients will eventually expression of COX-2 was recently shown to be an important die of their disease (1, 2). step in the multistep process of colorectal cancer carcino- The association between nonsteroidal anti-inflammatory genesis.
  • CELECOXIB Information That Patients Need to Know About Their Medication

    CELECOXIB Information That Patients Need to Know About Their Medication

    CELECOXIB Information That Patients Need to Know About Their Medication Kelsey L. Fletcher, BS Medical Student Wake Forest School of Medicine Winston-Salem, North Carolina Mary Lynn McPherson, PharmD, BCPS, CPE Professor and Vice Chair Department of Pharmacy Practice and Science University of Maryland, School of Pharmacy Baltimore, Maryland pain, cough or respiratory infections. Celecoxib may cause What is celecoxib? or worsen high blood pressure. Celecoxib (pronounced se le KOKS ib) is a nonsteroidal While taking celecoxib you should avoid drinking alco- anti-inflammatory drug (NSAID) that has been prescribed hol because it may increase your risk of stomach bleeding. by your doctor to relieve or prevent your pain. Celecoxib You should also avoid using celecoxib in combination with is available as an oral tablet. Another name you may see on other NSAIDs such as ibuprofen (Motrin, Advil), naproxen the prescription label is Celebrex. (Aleve), diclofenac (Arthrotec, Cambia, Cataflam, Voltaren) and others. Ask your doctor or pharmacist before taking What is it used for? other cold, allergy or pain medications, as they may contain Celecoxib is used for the management of acute pain in adults, medications similar to celecoxib. pain associated with menstrual cramps, and to treat the pain Celecoxib should not be used if you have a history of of arthritis including: allergic reaction to aspirin, sulfa drugs or other NSAIDs. If • Osteoarthritis taken for long periods of time, celecoxib can cause increased • Rheumatoid arthritis risk of cardiovascular events such as stroke and heart attack. • Juvenile rheumatoid arthritis in children over two Celecoxib may also have serious effects on the stomach and • Ankylosing spondylosis intestines, including bleeding and ulcers.
  • Cross-Reactivity to Acetaminophen and Celecoxib According to The

    Cross-Reactivity to Acetaminophen and Celecoxib According to The

    Original Article Allergy Asthma Immunol Res. 2014 March;6(2):156-162. http://dx.doi.org/10.4168/aair.2014.6.2.156 pISSN 2092-7355 • eISSN 2092-7363 Cross-reactivity to Acetaminophen and Celecoxib According to the Type of Nonsteroidal Anti-inflammatory Drug Hypersensitivity Yoon-Jeong Kim,1,2 Kyung-Hwan Lim,1,2 Mi-Young Kim,1,2 Eun-Jung Jo,1,2,3 Suh-Young Lee,1,2 Seung-Eun Lee,1,2,3 Min-Suk Yang,1,2,4 Woo-Jung Song,1,2 Hye-Ryun Kang,1,2 Heung-Woo Park,1,2 Yoon-Seok Chang,1,2,3 Sang-Heon Cho,1,2 Kyung-Up Min,1,2 Sae-Hoon Kim1,2,3,* 1Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea 2Institute of Allergy and Clinical Immunology, Seoul National University Medical Research Center, Seoul, Korea 3Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea 4Department of Internal Medicine, Seoul National University Boramae Medical Center, Seoul, Korea This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. Purpose: Identification of tolerable alternative analgesics is crucial for management in nonsteroidal anti-inflammatory drug (NSAID)-sensitive pa- tients. We investigated cross-reactivity of acetaminophen and celecoxib according to the type of aspirin/NSAID hypersensitivity and aimed to deter- mine the risk factors for cross-intolerance. Methods: We retrospectively reviewed the medical records of patients intolerant to aspirin and NSAIDs who had undergone an acetaminophen and/or celecoxib oral provocation test.
  • Non Steroidal Anti-Inflammatory Drugs

    Non Steroidal Anti-Inflammatory Drugs

    Non Steroidal Anti‐inflammatory Drugs (NSAIDs) 4 signs of inflammation • Redness ‐ due to local vessel dilatation • Heat ‐ due to local vessel dilatation • Swelling – due to influx of plasma proteins and phagocytic cells into the tissue spaces • Pain – due to local release of enzymes and increased tissue pressure NSAIDs • Cause relief of pain ‐. analgesic • Suppress the signs and symptoms of inflammation. • Exert antipyretic action. • Useful in pain related to inflammation. Esp for superficial/integumental pain . Classification of NSAIDs • Salicylates: aspirin, Sodium salicylate & diflunisal. • Propionic acid derivatives: ibuprofen, ketoprofen, naproxen. • Aryl acetic acid derivatives: diclofenac, ketorolac • Indole derivatives: indomethacin, sulindac • Alkanones: Nabumetone. • Oxicams: piroxicam, tenoxicam Classification of NSAIDs ….. • Anthranilic acid derivatives (fenamates): mefenamic acid and flufenamic acid. • Pyrazolone derivatives: phenylbutazone, oxyphenbutazone, azapropazone (apazone) & dipyrone (novalgine). • Aniline derivatives (analgesic only): paracetamol. Clinical Classif. • Non selective Irreversible COX inhibitors • Non slective Reversible COX inhibitors • Preferential COX 2 inhibitors • 10‐20 fold cox 2 selective • meloxicam, etodolac, nabumetone • Selective COX 2 inhibitors • > 50 fold COX ‐2 selective • Celecoxib, Etoricoxib, Rofecoxib, Valdecoxib • COX 3 Inhibitor? PCM Cyclooxygenase‐1 (COX‐1): -constitutively expressed in wide variety of cells all over the body. -"housekeeping enzyme" -ex. gastric cytoprotection, hemostasis Cyclooxygenase‐2 (COX‐2): -inducible enzyme -dramatically up-regulated during inflammation (10-18X) -constitutive : maintains renal blood flow and renal electrolyte homeostasis Salicylates Acetyl salicylic acid (aspirin). Kinetics: • Well absorbed from the stomach, more from upper small intestine. • Distributed all over the body, 50‐80% bound to plasma protein (albumin). • Metabolized to acetic acid and salicylates (active metabolite). • Salicylate is conjugated with glucuronic acid and glycine. • Excreted by the kidney.
  • Metabolic Profiling of Murine Plasma Reveals an Unexpected Biomarker In

    Metabolic Profiling of Murine Plasma Reveals an Unexpected Biomarker In

    Metabolic profiling of murine plasma reveals an unexpected biomarker in rofecoxib-mediated cardiovascular events Jun-Yan Liua, Ning Lib, Jun Yanga, Nan Lic, Hong Qiub, Ding Aia,c, Nipavan Chiamvimonvatb, Yi Zhuc, and Bruce D. Hammocka,1 aDepartment of Entomology and University of California-Davis Cancer Center and bDivision of Cardiovascular Medicine, University of California, Davis, CA 95616; and cDepartment of Physiology, Beijing University, Beijing 100083, People’s Republic of China Contributed by Bruce D. Hammock, August 6, 2010 (sent for review June 16, 2010) Chronic administration of high levels of selective COX-2 inhibitors infarction (MI), hypertension, and heart failure has also been ob- (coxibs), particularly rofecoxib, valdecoxib, and parecoxib, increases served to be associated with the administration of the nonaspirin risk for cardiovascular disease. Understanding the possibly multiple conventional NSAIDs, including but not limited to diclofenac, mechanisms underlying these adverse cardiovascular events is critical ibuprofen, naproxen, and indomethacin (8–12). In addition, there for evaluating the risks and benefits of coxibs and for development of could be rofecoxib-specific events such as the facile formation of safer coxibs. The current understanding of these mechanisms is likely a cardiotoxic maleic anhydride derivative from rofecoxib that may incomplete. Using a metabolomics approach, we demonstrate that contribute to its adverse effects (13). This hypothesis fails to ex- oral administration of rofecoxib for 3 mo results in a greater than 120- plain the increased risk in the cardiovascular system from other fold higher blood level of 20-hydroxyeicosatetraenoic acid (20-HETE), nonaspirin NSAIDs. Thus, current mechanisms provide an in- fi which correlates with a signi cantly shorter tail bleeding time in complete explanation for cardiovascular problems associated with a murine model.
  • Celecoxib) Capsules the Risk Is Greater in Patients with a Prior History of Ulcer Disease Or Initial U.S

    Celecoxib) Capsules the Risk Is Greater in Patients with a Prior History of Ulcer Disease Or Initial U.S

    HIGHLIGHTS OF PRESCRIBING INFORMATION ------------------------WARNINGS AND PRECAUTIONS------------------------- • Serious and potentially fatal cardiovascular (CV) thrombotic events, These highlights do not include all the information needed to use myocardial infarction, and stroke. Patients with known CV CELEBREX safely and effectively. See full prescribing information disease/risk factors may be at greater risk (5.1, 14.7, 17.2). for CELEBREX. • Serious gastrointestinal (GI) adverse events, which can be fatal. ® CELEBREX (celecoxib) capsules The risk is greater in patients with a prior history of ulcer disease or Initial U.S. Approval: 1998 GI bleeding, and in patients at high risk for GI events, especially the elderly. CELEBREX should be used with caution in these patients WARNING: CARDIOVASCULAR AND GASTROINTESTINAL RISKS (5.4, 8.5, 14.7, 17.3). See full prescribing information for complete boxed warning • Elevated liver enzymes and, rarely, severe hepatic reactions. Cardiovascular Risk Discontinue use of CELEBREX immediately if abnormal liver • CELEBREX, may cause an increased risk of serious enzymes persist or worsen (5.5, 17.4). cardiovascular thrombotic events, myocardial infarction, and • New onset or worsening of hypertension. Blood pressure should stroke, which can be fatal. All NSAIDs may have a similar risk. be monitored closely during treatment with CELEBREX This risk may increase with duration of use. Patients with (5.2, 7.4, 17.2). cardiovascular disease or risk factors for cardiovascular • disease may be at greater risk. (5.1,14.7) Fluid retention and edema. CELEBREX should be used with caution • CELEBREX is contraindicated for the treatment of peri-operative in patients with fluid retention or heart failure (5.3, 17.6).
  • Bextra, INN-Valdecoxib

    Bextra, INN-Valdecoxib

    ANNEX I SUMMARY OF PRODUCT CHARACTERISTICS 1 1. NAME OF THE MEDICINAL PRODUCT Bextra 10 mg film-coated tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each film-coated tablet contains 10 mg valdecoxib. For excipients, see section 6.1. 3. PHARMACEUTICAL FORM Film-coated tablets White, capsule-shaped, debossed ‘10’ on one side and ‘7815’ on the other. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Symptomatic relief in the treatment of osteoarthritis or rheumatoid arthritis. Treatment of primary dysmenorrhoea. 4.2 Posology and method of administration Bextra is administered orally. Bextra may be taken with or without food (see section 5.2). Osteoarthritis and rheumatoid arthritis: The recommended dose is 10 mg once daily. Some patients may receive additional benefit from 20 mg once daily. The maximum recommended dose is 20 mg once daily. Treatment of primary dysmenorrhoea: The recommended dose for symptomatic relief is 40 mg once daily as required. On the first day of treatment, an additional 40 mg dose may be taken if needed. Thereafter, the maximum recommended dose is 40 mg once daily. Elderly: For elderly patients (≥ 65 years), in particular those of less than 50 kg body weight, initiate therapy at the lowest recommended dose for osteoarthritis and rheumatoid arthritis (10 mg once daily) (see section 5.2). Hepatic Impairment: No dosage adjustment is generally necessary in patients with mild hepatic impairment (Child-Pugh score 5-6). In patients with moderate hepatic impairment (Child-Pugh score 7- 9 ) treatment should be initiated with caution. The lowest recommended dose should be used for osteoarthritis and rheumatoid arthritis (10 mg once daily) and the dosage should not exceed 20 mg for primary dysmenorrhoea.
  • Aspirin and Other Anti-Inflammatory Drugs

    Aspirin and Other Anti-Inflammatory Drugs

    Thorax 2000;55 (Suppl 2):S3–S9 S3 Aspirin and other anti-inflammatory drugs Thorax: first published as 10.1136/thorax.55.suppl_2.S3 on 1 October 2000. Downloaded from Sir John Vane Historical introduction inhibiting COX, thereby reducing prosta- Salicylic acid, the active substance in plants glandin formation, providing a unifying expla- used for thousands of years as medicaments, nation for their therapeutic actions and their was synthesised by Kolbe in Germany in 1874. side eVects. This also firmly established certain MacLagan1 and Stricker2 showed that it was prostaglandins as important mediators of eVective in rheumatic fever. A few years later inflammatory disease (see reviews by Vane and sodium salicylate was also in use as a treatment Botting7 and Vane et al8). COX first cyclises for chronic rheumatoid arthritis and gout as arachidonic acid to form prostaglandin (PG) well as an antiseptic compound. G2 and the peroxidase part of the enzyme then Felix HoVman was a young chemist working reduces PGG2 to PGH2. at Bayer. Legend has it that his father, who was taking salicylic acid to treat his arthritis, Discovery of COX-2 complained to his son about its bitter taste. Over the next 20 years several groups postu- Felix responded by adding an acetyl group to lated the existence of isoforms of COX. Then salicylic acid to make acetylsalicylic acid. Rosen et al,9 studying COX in epithelial cells Heinrich Dreser, the Company’s head of phar- from the trachea, found an increase in activity macology, showed it to be analgesic, anti- of COX during prolonged cell culture.