DOCSLIB.ORG

Flufenamic Acid in Rheumatoid Arthritis

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Flufenamic Acid in Rheumatoid Arthritis Ann Rheum Dis: first published as 10.1136/ard.26.1.43 on 1 January 1967. Downloaded from Ann. rheum. Dis. (1967), 26, 43 FLUFENAMIC ACID IN RHEUMATOID ARTHRITIS BY K. T. RAJAN, A. G. S. HILL, A. BARR, AND E. WHITWELL From the Oxford Regional Rheumatic Diseases Research Centre, and the Statistical Department, Oxford Regional Hospital Board This is a report of a clinical trial comparing number of joints involved, but aspirin appeared to the effects in patients with rheumatoid arthritis of an be more effective in reducing the erythrocyte sedi- anti-inflammatory drug, flufenamic acid, with the mentation rate (ESR). The same authors observed familiar anti-rheumatic drugs phenylbutazone and a steady fall in the average ESR in a group of soluble aspirin. patients treated with flufenamic acid for longer Flufenamic acid, N-(aaa-trifluoro-m-tolyl) an- periods, but this part of the trial was not controlled. thranilic acid, is a stable, weak carboxylic acid with In another trial, Fearnley and Masheter (1966) com- the formula shown in Fig. 1. pared prednisone (7 5 mg. daily) with flufenamic acid (600 mg. daily) in two groups of patients with COOH CF3 active rheumatoid arthritis. Prednisone proved copyright. N H/ NH more effective in reducing the number of joints involved and in increasing the strength of grip; it also markedly reduced the average ESR whereas flufena- Fig. 1.-Chemical formula of flufenamic acid. mic acid did not influence this measurement. It is a cream-coloured solid supplied in 200 mg. Barnardo, Currey, Mason, Fox, and Weatherall capsules. In experiments with guinea-pigs and rats its (1966) compared mefenamic acid and flufenamic acid with anti-inflammatory activity as determined by the aspirin and phenylbutazone in female out- http://ard.bmj.com/ ultra-violet erythema test has been shown by patients with rheumatoid arthritis; phenylbutazone Winder, Wax, Serrano, Jones, and McPhee (1963) to was preferred slightly but not significantly more often be approximately 1 *6 times that of phenylbutazone than any other drug and flufenamic acid was least and 16 times that of aspirin. It has a dose-graded popular, but again not significantly. The design of effect 3 * 6 times greater than phenylbutazone. Oral this trial provided for adjustment of dosage to the doses in excess of expected therapeutic levels are said need of individual patients and equipotent daily to be very well tolerated and diarrhoea has been the doses of the trial drugs were estimated as 2 - 4 g. for commonest adverse effect. In a double-blind con- aspirin, 0 * 33 g. for phenylbutazone, 1 * 7 g. for on September 24, 2021 by guest. Protected trolled trial comparing flufenamic acid with aspirin mefenamic acid, and 0-67 g. for flufenamic acid. in a small number of patients with rheumatoid arthritis, Coodley (1963) found that the former, in a Purpose of Present Trial total daily dosage of 300 mg., was superior in its In the trial now reported the ability of the three effect on strength of grip and other parameters. The drugs, flufenamic acid, phenylbutazone, and aspirin, total daily dose of aspirin, however, was only 1,800 to lessen pain provided the principal basis for com- mg. Higher daily doses of flufenamic acid (600 mg.) parison. The trial was so designed as to allow it to were found by Young (1963) to have an effect equal be concluded as soon as a statistically significant to that of oxyphenbutazone (400 mg.). More difference had been established or a sufficient number recently Simpson, Simpson, and Masheter (1966) of cases accumulated to show that no such difference completed a trial, of double-blind cross-over design, existed. It was accepted that the number of obser- comparing flufenamic acid (600 mg.) with aspirin vations might not suffice for a significant difference (2,700 mg.). Little difference was noted between to emerge between the effects of the drugs on the the effect of the two drugs on strength of grip or other parameters which were to be measured. 43 Ann Rheum Dis: first published as 10.1136/ard.26.1.43 on 1 January 1967. Downloaded from 44 ANNALS OF THE RHEUMATIC DISEASES Methods Results Patients admitted to the trial all satisfied the criteria of (a) Subjective Response.-The sequential charts the American Rheumatism Association (Ropes, Bennett, (Fig. 2a, b and c, opposite) show the three two-way Cobb, Jacox, and Jessar, 1958) for a diagnosis of definite comparisons between the drugs used in the trial, based rheumatoid arthritis. All had pain in one or more joints and none had a history of any adverse reaction to aspirin on the patients' own assessment of the severity of or phenylbutazone. On entry to the trial patients symptoms. No significant difference emerged in any already taking a corticosteroid continued this treatment comparison, though there was a tendency for without alteration of dose; otherwise only the trial drugs phenylbutazone to be preferred by more patients were administered. than either of the other two drugs. Formal analysis The trial, which was double-blind, lasted 6 weeks and (Table I) confirms that there was little to choose each drug was given for 2 weeks of this period. The between aspirin and flufenamic acid and that the lead sequence of drugs was varied according to a pre-deter- of phenylbutazone over each of the other drugs was mined random code and the total daily intake of each not significant (P > 0 1). drug, divided into three equal doses, was as follows: Flufenamic acid 600 mg. TABLE I Phenylbutazone 300 mg. COMPARISONS OF THE PATIENTS' PREFERENCE BETWEEN Aspirin 3.0 g. PAIRS OF DRUGS Three capsules were required for a single dose of aspirin Observed Expected No. but only one for the other two drugs. To avoid varying Preference No. of on Null x2 P(>) Patients Hypothesis the number of capsules forming a single dose patients were instructed to take a capsule from one bottle and two Abetter than B 14 13 RhbetterthanA 12 13 0*15 0*50 from a second. When aspirin was being administered the capsules in both bottles contained this drug but during TOTAL 26 26 an other periods those in the second bottle contained A better thanC 10 13 5 1*88 0 10 inert substance. All patients were seen at fortnightly CbetterthanA 17 13-5 intervals and were initially issued with numbered pre- TOTAL 27 27 copyright. bottles and instructions as to the number of packed B better than C 9 13 2*46 0*10 capsules to be taken. They were asked to return the CbetterthanB 17 13 bottles at the end of the for which had been fortnight they TOTAL 26 26 earmarked and any unused capsules were then counted. Only two patients returned capsules, numbering four and A = Flufenamic acid six respectively. At each visit a record was made of the B = Aspirin strength of grip measured in mm. Hg with a pneumatic C = Phenylbutazone bag inflated to 20 or 30 mm. Any adverse reactions were http://ard.bmj.com/ recorded and blood was taken for determination of the Less weight can be attached to the patients' ESR by Westergren's method. At the end of 4 and 6 overall preferences recorded at the end of the trial, weeks patients were asked to say whether their pain had since this involved the difficult task of casting back increased or decreased at the time of change-over of drugs. When the trial ended they were also asked to say over the whole period. In fact nine chose flufenamic whether they could identify any period as preferable to acid, seven aspirin, and eleven phenylbutazone. the others in terms of subjective relief. Wherever (b) Strength ofGrip.-The effect of the trial drugs possible all assessments were made by one observer. A sequential design was adopted for analysing subjec- on strength of grip was examined in a similar way to on September 24, 2021 by guest. Protected tive responses to the drugs, a separate chart being used that used in assessing the subjective response. for each of the possible three-way comparisons. The Separate analyses were also made for each pair of boundaries of these charts were drawn so that if one drugs given consecutively or separated by a period of treatment was preferred 35 per cent. more than another treatment with the third drug. No statistically there would be a 95 per cent. chance of detecting the significant difference emerged from any of these difference. Such a design allows a trial to be concluded analyses. There was a tendency for the grip to im- quickly if one treatment is overwhelmingly preferred to prove more during treatment with phenylbutazone, another. In the present instance a boundary on each results for each hand considered chart had been crossed by the time 27 patients had com- but the separately pleted the trial. Three patients failed to complete the were inconsistent in assigning the other two drugs to trial: one suffered an acute exacerbation of her arthritis second and third place. during the first week and had her treatment altered by her general practitioner, and the other two failed to attend (c) Erythrocyte Sedimentation Rate.-A similar for their fortnightly assessment. No patient had to stop analysis of the ESR again showed no statistically the trial because of an adverse reaction to any of the three significant difference, though there was a greater drugs. tendency for the rate to decrease during treatment Ann Rheum Dis: first published as 10.1136/ard.26.1.43 on 1 January 1967. Downloaded from FLUFENAMIC ACID 45 20 20 15 - Flufenamic acid preferred to phenylbutazone 5 ] Aspirin preferred to phenylbutozone 10 10 5 c u - 5 u4 -5 U.'- 5 XL - S - 10 -10 - I5 - 1 5- Phenylbutozone preferred to flufenamic acid Phenylbutazone preferred to aspirin Is /-% 2 (a) 2 - 20- - 20i x C) Fig.
Load more

Recommended publications
  • Colitis Caused by Non-Steroidal Anti-Inflammatory Drugs
    Postgrad Med J: first published as 10.1136/pgmj.62.730.773 on 1 August 1986. Downloaded from Postgraduate Medical Journal (1986) 62, 773-776 Colitis caused by non-steroidal anti-inflammatory drugs S. Ravi', A.C. Keat2 and E.C.B. Keat1 'Cuckfield Hospital, Cuckfield, West Sussex, and2Westminster Hospital, Horseferry Road, London SWIP2AP, UK. Summary: Four cases of acute proctocolitis associated with non-steroidal anti-inflammatory drug therapy are presented. The drugs implicated were flufenamic acid, mefenamic acid, naproxen and ibuprofen. After resolution of symptoms and signs of proctocolitis three of the four patients were subsequently rechallenged with the implicated drug: in each there was a rapid relapse. Introduction Ulcerative colitis is a disease of unknown aetiology Case reports with characteristic clinical features and a protracted course. A similar clinical picture, but running a shorter Case I and usually benign course, is occasionally seen follow- ing the administration of certain drugs. This was first A 77 year old woman was referred with intermittent noticed following the administration of antibiotics, bleeding per rectum for 6 months, associated for the often with pseudomembrane formation. Later, this last 2 months with bloody diarrhoea up to eight times was shown to be associated with infection by toxigenic daily. Previously, she had had troublesome symptoms Clostridium difficile. Until 1978, most cases were from osteoarthritis of her back and knees for which copyright. associated with treatment with clindamycin but since she had been prescribed flufenamic acid 200 mg thrice that time nearly all antibiotics have been implicated. daily. Her general health had remained good but she Other drugs capable of causing proctocolitis, though appeared pale and her haemoglobin was reduced to by different mechanisms, include phenindione (Keat & 8 g/dl.
    [Show full text]
  • Investigating the Influence of Polymers on Supersaturated
    Page 1 of 45 Molecular Pharmaceutics 1 2 3 4 5 6 7 Investigating the Influence of Polymers on 8 9 10 11 12 Supersaturated Flufenamic Acid Cocrystal Solutions 13 14 15 16 1 1 2 2 1 17 Minshan Guo , Ke Wang , Noel Hamill , Keith Lorimer and Mingzhong Li * 18 19 20 1School of pharmacy, De Montfort University, Leicester, UK 21 22 23 2Almac Science, Seagoe Industrial Estate, Craigavon, UK 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 ACS Paragon Plus Environment 1 Molecular Pharmaceutics Page 2 of 45 1 2 3 4 5 6 7 Table of contents graphic 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 ACS Paragon Plus Environment 2 Page 3 of 45 Molecular Pharmaceutics 1 2 3 Abstract 4 5 6 7 The development of enabling formulations is a key stage when demonstrating the effectiveness 8 9 10 of pharmaceutical cocrystals to maximize the oral bioavailability for poorly water soluble drugs. 11 12 Inhibition of drug crystallization from a supersaturated cocrystal solution through a fundamental 13 14 understanding of the nucleation and crystal growth is important. In this study, the influence of 15 16 17 the three polymers of polyethylene glycol (PEG), polyvinylpyrrolidone (PVP) and a copolymer 18 19 of N-vinly-2-pyrrodidone (60%) and vinyl acetate (40%) (PVP-VA) on the flufenamic acid 20 21 22 (FFA) crystallization from three different supersaturated solutions of the pure FFA and two 23 24 cocrystals of FFA-NIC CO and FFA-TP CO has been investigated by measuring nucleation 25 26 induction times and desupersaturation rates in the presence and absence of seed crystals.
    [Show full text]
  • Big Pain Assays Aren't a Big Pain with the Raptor Biphenyl LC Column
    Featured Application: 231 Pain Management and Drugs of Abuse Compounds in under 10 Minutes by LC-MS/MS Big Pain Assays Aren’t a Big Pain with the Raptor Biphenyl LC Column • 231 compounds, 40+ isobars, 10 drug classes, 22 ESI- compounds in 10 minutes with 1 column. • A Raptor SPP LC column with time-tested Restek Biphenyl selectivity is the most versatile, multiclass-capable LC column available. • Achieve excellent separation of critical isobars with no tailing peaks. • Run fast and reliable high-throughput LC-MS/MS analyses with increased sensitivity using simple mobile phases. The use of pain management drugs is steadily increasing. As a result, hospital and reference labs are seeing an increase in patient samples that must be screened for a wide variety of pain management drugs to prevent drug abuse and to ensure patient safety and adherence to their medication regimen. Thera- peutic drug monitoring can be challenging due to the low cutoff levels, potential matrix interferences, and isobaric drug compounds. To address these chal- lenges, many drug testing facilities are turning to liquid chromatography coupled with mass spectrometry (LC-MS/MS) for its increased speed, sensitivity, and specificity. As shown in the analysis below, Restek’s Raptor Biphenyl column is ideal for developing successful LC-MS/MS pain medication screening methodologies. With its exceptionally high retention and unique selectivity, 231 multiclass drug compounds and metabolites—including over 40 isobars—can be analyzed in just 10 minutes. In addition, separate panels have been optimized on the Raptor Biphenyl column specifically for opioids, antianxiety drugs, barbiturates, NSAIDs and analgesics, antidepressants, antiepileptics, antipsychotics, hallucinogens, and stimulants for use during confirmation and quantitative analyses.
    [Show full text]
  • Flufenamic Acid, Mefenamic Acid and Niflumic Acid Inhibit Single Nonselective Cation Channels in the Rat Exocrine Pancreas
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Volume 268, number 1, 79-82 FEBS 08679 July 1990 Flufenamic acid, mefenamic acid and niflumic acid inhibit single nonselective cation channels in the rat exocrine pancreas H. Gagelein*, D. Dahlem, H.C. Englert** and H.J. Lang** Max-Planck-Institutfir Biophysik, Kennedyallee 70, D-600 Frankfurt/Main 70, FRG Received 17 May 1990 The non-steroidal anti-inflammatory drugs, flufenamic acid, mefenamic acid and niflumic acid, block Ca2+-activated non-selective cation channels in inside-out patches from the basolateral membrane of rat exocrine pancreatic cells. Half-maximal inhibition was about 10 PM for flufenamic acid and mefenamic acid, whereas niflumic acid was less potent (IC,, about 50 PM). Indomethacin, aspirin, diltiazem and ibuprofen (100 /IM) had not effect. It is concluded that the inhibitory effect of flufenamate, mefenamate and niflumate is dependent on the specific structure, consisting of two phenyl rings linked by an amino bridge. Mefenamic acid; Flufenamic acid; Niflumic acid; Indomethacin; Non-selective cation channel; Rat exocrine pancreas 1. INTRODUCTION indomethacin, ibuprofen, diltiazem and acetylsalicylic acid (aspirin) were obtained from Sigma (Munich, FRG). The substances were dissolved in dimethylsulfoxide (DMSO, Merck, Darmstadt, FRG, Recently it was reported that the drug, 3 ’ ,5-dichloro- 0.1% of total volume) before addition to the measuring solution. diphenylamine-2-carboxylic acid (DCDPC), blocks DMSO alone had no effect on the single channel recordings. non-selective cation channels in the basolateral mem- 2.2. Methods brane of rat exocrine pancreatic cells [ 11.
    [Show full text]
  • Synthesis and Pharmacological Evaluation of Fenamate Analogues: 1,3,4-Oxadiazol-2-Ones and 1,3,4- Oxadiazole-2-Thiones
    Scientia Pharmaceutica (Sci. Pharm.) 71,331-356 (2003) O Osterreichische Apotheker-Verlagsgesellschaft m. b.H., Wien, Printed in Austria Synthesis and Pharmacological Evaluation of Fenamate Analogues: 1,3,4-Oxadiazol-2-ones and 1,3,4- Oxadiazole-2-thiones Aida A. ~l-~zzoun~'*,Yousreya A ~aklad',Herbert ~artsch~,~afaaA. 2aghary4, Waleed M. lbrahims, Mosaad S. ~oharned~. Pharmaceutical Sciences Dept. (Pharmaceutical Chemistry goup' and Pharmacology group2), National Research Center, Tahrir St. Dokki, Giza, Egypt. 3~nstitutflir Pharmazeutische Chemie, Pharrnazie Zentrum der Universitilt Wien. 4~harmaceuticalChemistry Dept. ,' Organic Chemistry Dept. , Helwan University , Faculty of Pharmacy, Ein Helwan Cairo, Egypt. Abstract A series of fenamate pyridyl or quinolinyl analogues of 1,3,4-oxadiazol-2-ones 5a-d and 6a-r, and 1,3,4-oxadiazole-2-thiones 5e-g and 6s-v, respectively, have been synthesized and evaluated for their analgesic (hot-plate) , antiinflammatory (carrageenin induced rat's paw edema) and ulcerogenic effects as well as plasma prostaglandin E2 (PGE2) level. The highest analgesic activity was achieved with compound 5a (0.5 ,0.6 ,0.7 mrnolkg b.wt.) in respect with mefenamic acid (0.4 mmollkg b.wt.). Compounds 6h, 61 and 5g showed 93, 88 and 84% inhibition, respectively on the carrageenan-induced rat's paw edema at dose level of O.lrnrnol/kg b.wt, compared with 58% inhibition of mefenamic acid (0.2mmoll kg b.wt.). Moreover, the highest inhibitory activity on plasma PGE2 level was displayed also with 6h, 61 and 5g (71, 70,68.5% respectively, 0.lmmolkg b.wt.) compared with indomethacin (60%, 0.01 mmolkg b.wt.) as a reference drug.
    [Show full text]
  • Comparative Study of the Efficacy of Flunixin, Ketoprofen and Phenylbutazone in Delman Horses with Mild Colic
    Sys Rev Pharm 2020; 11(5): 464 468 A multifaceted review journal in the field of pharmacy E-ISSN 0976-2779 P-ISSN 0975-8453 Comparative Study of the Efficacy of Flunixin, Ketoprofen and Phenylbutazone in Delman Horses with Mild Colic Agus Purnomo1, Arya Pradana Wicaksono2, Dodit Hendrawan2, Muhammad Thohawi Elziyad Purnama3* 1Department of Veterinary Surgery and Radiology, Faculty of Veterinary Medicine, Universitas Gadjah Mada, DI Yogyakarta, 55281, Indonesia 2Postgraduate Studies, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, 60115, Indonesia 3Department of Veterinary Anatomy, Faculty of Veterinary Medicine, Universitas Airlangga, Surabaya, 60115, Indonesia *Corresponding author E-mail: [email protected] Article History: Submitted: 26.02.2020 Revised: 16.04.2020 Accepted: 21.05.2020 ABSTRACT This study aimed to evaluate the efficacy of flunixin, ketoprofen and multiple range test. The results showed a significant alleviation in all phenylbutazone on serum biochemistry, plasma catecholamines and observed variables on Day 13, although the use of various NSAIDs serum cortisol in Delman horses with mild colic. During the study showed no significant difference. period, 32 horses were evaluated due to mild colic. Flunixin, Keywords: serum biochemical, catecholamine, cortisol, colic, NSAIDs ketoprofen, and phenylbutazone were administered intravenously at Correspondence: the recommended dose rates of 1.0; 2.2 and 4.4 mg/kg, respectively. Muhammad Thohawi Elziyad Purnama Administration of the NSAIDs commenced on Day 1 and continued Department of Veterinary Anatomy, Faculty of Veterinary Medicine, every 12 h for 12 days. Blood samples collected between days 2, 5, 9 Universitas Airlangga, Surabaya, 60115, Indonesia and 13 to evaluate AST, ALP, GGT, creatinine, urea, epinephrine, E-mail: [email protected] norepinephrine, and cortisol level.
    [Show full text]
  • Non-Steroidal Anti-Inflammatory Drugs (Nsaids)
    NON-STEROIDAL ANTI-INFLAMMATORY DRUGS ANALYSIS IN MILK BY QUECHERS AND LC-MS: LOW AND HIGH RESOLUTION DETECTION AND CONFIRMATION APPROACHES A. Rúbies1, L. Guo2, I. Beguiristain1, F. Centrich1, M. Granados2 1. Laboratori Agència de Salut Pública de Barcelona, 2. Departament de Química Analítica - Universitat de Barcelona. * INTRODUCTION NON-STEROIDAL ANTI-INFLAMATORY DRUGS (NSAIDs) Non-steroidal anti-inflammatory drugs (NSAIDs) are used as anti-inflammatory, analgesic and OXICAMS ANTHRANILIC ACID DERIVATIVES ACETIC ACID antipyretic drugs in medicine and veterinary. Their action mechanism is based on the blocking of PROPIONIC ACID DERIVATIVES DERIVATIVES the biosynthesis of prostaglandins. NSAIDs are highly effective and extensively used, but they have some adverse side effects, such as hepatotoxicity, renal disorders or allergic reactions. In the European Union, to assure food safety and protect consumers, maximum residue limits have been established for some authorised NSAIDs in food products. Therefore, high throughput and reliable analytical methodology is required for the effective control of NSAIDs in food from animal Flufenamic acid origin. Liquid chromatography (LC) coupled to mass spectrometry (MS) is currently the technique of choice in confirmatory analysis of NSAIDs residues. We present a new method for the determination of representative NSAIDs in milk based on QuEChERS methodology, LC-MS/MS and UHPLC-HRMS. Meloxicam Ketoprofen Diclofenac EU Maximum Residue Limits (MRLs) Recommended NSAIDs concentrations for NSAIDs in milk.
    [Show full text]
  • Choice of Drugs in the Treatment of Rheumatoid Arthritis
    RHEUMATOLOGY IN GENERAL PRACTICE 7 Those with predominant but never exclusive involvement of the terminal finger joint, usually associated with changes in the nail of the same finger; they are serologically negative. There may be a swollen finger with loss of the skin markings-a sort of dactylitis, again serologically negative. (2) Those with a much more severe process which produces loss of movement in the spine and changes in the sacroiliac joints much the same as those in ankylosing spondylitis; unlike ankylosing spondylitis, it produces severe deformity often with ankylosis in peripheral joints. Many of the finger joints become deformed and ankylosed. (3) Those cases indistinguishable from rheumatoid arthritis although the majority are sero-negative. The Stevens Johnson syndrome produces acute effusions, particularly in large joints. It is sometimes associated with the rash of erythema multiforme, always with ulceration in the mouth and genital tract; the mouth ulcers are accompanied by sloughing, unlike those of Beh9et's syndrome which we come to next. BehCet's syndrome, originally described as a combination of orogenital ulceration with relapsing iritis, is now expanded to include skin lesions, other eye lesions, lesions of the central nervous system, thrombophlebitis migrans, and arthropathy (occurring in 64 per cent). The onset is acute, often affecting only a single joint and settling without residual trouble. Choice of drugs in the treatment of rheumatoid arthritis Dr Dudley Hart, M.D., F.R.C.P. (Consultant physician, Westminster Hospital and Medical School) There are many potential drugs for the treatment of rheumatoid disease, but what are we treating in this disorder? Pain in rheumatoid arthritis is but one of the symp- toms.
    [Show full text]
  • 21225 Mirena Clinical PREA
    CLINICAL REVIEW Application Type NDA Application Number 21-225 (SE1- Applicant submission 027) Priority or Standard Priority Submit Date March 31, 2009 Received Date April 1, 2009 PDUFA Goal Date October 1, 2009 Division / Office Division of Reproductive and Urologic Products (DRUP) / Office of Drug Evaluation III (ODE III) Reviewer Name Gerald Willett M.D. Review Completion Date September 16, 2009 Established Name Levonorgestrel-releasing intrauterine system (LNG IUS) Trade Name Mirena® Therapeutic Class Progestin-containing intrauterine device Applicant Bayer HealthCare Pharmaceuticals Inc. Formulation Intrauterine device Dosing Regimen Insertion into the uterine cavity (5 year contraceptive efficacy) Indication Treatment of heavy menstrual bleeding for women who choose to use intrauterine contraception as their method of contraception Intended Population Women of childbearing age Template Version: March 6, 2009 Clinical Review Gerald Willett, M.D. NDA 21-225, SE1 Mirena® (levonorgestrel-releasing intrauterine system) Table of Contents 1 RECOMMENDATIONS/RISK BENEFIT ASSESSMENT....................................... 10 1.1 Recommendation on Regulatory Action ........................................................... 10 1.2 Risk Benefit Assessment.................................................................................. 10 1.3 Recommendations for Postmarket Risk Evaluation and Mitigation Strategies . 13 1.4 Recommendations for Postmarket Requirements and Commitments .............. 13 2 INTRODUCTION AND REGULATORY BACKGROUND .....................................
    [Show full text]
  • In 1977 a Conclusion of the National Association of State Racing Commissioners Veterinary-Chemist Advisory Board Concluded That
    Lawrence R. Soma, VMD, University of Pennsylvania, School of Veterinary Medicine. This review was undertaken at the request of the Racing Medication and Testing Consortium, Medication Advisory Committee. Review: The use of phenylbutazone in the horse This review presents a brief historical prospective of the genesis of regulated medication in the US racing industry of which the non-steroidal anti-inflammatory drug phenylbutazone (PBZ) is the focus. It presents some historical guide posts in the development of the current rules on the use on PBZ by racing jurisdictions in the US. Based on its prevalent use, PBZ still remains a focus of attention. The review examines the information presented in a number of different models used to determine the effects and duration of PBZ in the horse. They include naturally occurring lameness and reversible induced lameness models that directly examine the effects and duration of the administration of various doses of PBZ. The review also examines indirect plasma and tissue models studying the suppression of the release of arachidonic acid- derived mediators of inflammation. The majority of studies suggest an effect of PBZ at 24 hours at 4.4 mg/kg. This reflects and substantiates the opinion of many clinical veterinarians, many of whom will not perform a pre-purchase lameness examination unless the horse is shown to be free of NSAID. This remains the opinion of many Commission Veterinarians in that they wish to examine a horse pre-race without the possibility of a NSAID interfering with the examination and masking possible musculoskeletal conditions. Based on scientific studies, residual effects of PBZ remain at 24 hours following administration.
    [Show full text]
  • Guideline for Preoperative Medication Management
    Guideline: Preoperative Medication Management Guideline for Preoperative Medication Management Purpose of Guideline: To provide guidance to physicians, advanced practice providers (APPs), pharmacists, and nurses regarding medication management in the preoperative setting. Background: Appropriate perioperative medication management is essential to ensure positive surgical outcomes and prevent medication misadventures.1 Results from a prospective analysis of 1,025 patients admitted to a general surgical unit concluded that patients on at least one medication for a chronic disease are 2.7 times more likely to experience surgical complications compared with those not taking any medications. As the aging population requires more medication use and the availability of various nonprescription medications continues to increase, so does the risk of polypharmacy and the need for perioperative medication guidance.2 There are no well-designed trials to support evidence-based recommendations for perioperative medication management; however, general principles and best practice approaches are available. General considerations for perioperative medication management include a thorough medication history, understanding of the medication pharmacokinetics and potential for withdrawal symptoms, understanding the risks associated with the surgical procedure and the risks of medication discontinuation based on the intended indication. Clinical judgement must be exercised, especially if medication pharmacokinetics are not predictable or there are significant risks associated with inappropriate medication withdrawal (eg, tolerance) or continuation (eg, postsurgical infection).2 Clinical Assessment: Prior to instructing the patient on preoperative medication management, completion of a thorough medication history is recommended – including all information on prescription medications, over-the-counter medications, “as needed” medications, vitamins, supplements, and herbal medications. Allergies should also be verified and documented.
    [Show full text]
  • Nonsteroidal Anti-Inflammatory Agents Differ in Their Ability to Suppress
    Oncogene (2004) 23, 9247–9258 & 2004 Nature Publishing Group All rights reserved 0950-9232/04 $30.00 www.nature.com/onc Nonsteroidal anti-inflammatory agents differ in their ability to suppress NF-jB activation, inhibition of expression of cyclooxygenase-2 and cyclin D1, and abrogation of tumor cell proliferation Yasunari Takada1, Anjana Bhardwaj1, Pravin Potdar1 and Bharat B Aggarwal*,1 1Cytokine Research Laboratory, Department of Experimental Therapeutics, The University of Texas M.D. Anderson Cancer Center, Box 143, 1515 Holcombe Boulevard, Houston, TX 77030, USA Nonsteroidal anti-inflammatory drugs (NSAIDs) such as Introduction aspirin have been shown to suppress transcription factor NF-jB, which controls the expression of genes such as Owing to its analgesic and anti-inflammatory effects, cyclooxygenase (COX)-2 and cyclin D1, leading to aspirin (acetylsalicylic acid), first synthesized in 1897, inhibition of proliferation of tumor cells. There is no was approved for the treatment of rheumatoid arthritis systematic study as to how these drugs differ in their ability in 1899 (Botting, 1999). Since then several other to suppress NF-jB activation and NF-jB-regulated gene nonsteroidal anti-inflammatory drugs (NSAIDs) have expression or cell proliferation. In the present study, we been synthesized and approved for human use. The anti- investigated the effect of almost a dozen different commonly inflammatory and analgesic effects of NSAIDs have used NSAIDs on tumor necrosis factor (TNF)-induced NF- been shown to be due to their ability to inhibit the jB activation and NF-jB-regulated gene products, and on enzymatic activity of cyclooxygenases (COXs), which cell proliferation. Dexamethasone, an anti-inflammatory convert arachidonic acid to prostaglandins (PGs) (Vane, steroid, was included for comparison with NSAIDs.
    [Show full text]