DOCSLIB.ORG

Adverse Drug Reactions Associated with the Use of Nsaids: a Case

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Adverse Drug Reactions Associated with the Use of Nsaids: a Case doi: 10.1111/j.1472-8206.2011.00991.x ORIGINAL Adverse drug reactions associated with the ARTICLE use of NSAIDs: a case/noncase analysis of gy spontaneous reports from the French lo pharmacovigilance database 2002–2006 o Maryse Lapeyre-Mestrea,b,c*, Sabrina Grolleaua,b, c Jean-Louis Montastruc a,b,c, Association Franc¸aise des Centres Re´gionaux a de Pharmacovigilance (CRPV)a a m Service de Pharmacologie Clinique, Centre Midi-Pyre´ne´es de Pharmacovigilance, de Pharmacoe´pide´miologie et d’Information sur le Me´dicament, Hoˆpitaux de Toulouse, Toulouse, France r bFaculte´ de Me´decine, Universite´ Paul Sabatier, Universite´ de Toulouse, Toulouse, France a cUnite´ mixte INSERM 1027, Equipe de Pharmacoe´pide´miologie, Toulouse, Toulouse, France h P Keywords ABSTRACT adverse drug reactions, gastrointestinal system, To evaluate the safety profile of eight oral nonsteroidal anti-inflammatory drugs liver, (NSAIDs) available in France, using data reported through the French pharmaco- NSAID(s), vigilance system. Data (from 2002 to 2006) were analysed for aceclofenac, seriousness, diclofenac, ketoprofen, meloxicam, naproxen, nimesulide, piroxicam and tenoxicam, Clinical skin focusing on the reported rates of serious adverse drug reactions (ADRs) in the following system organ classes: gastrointestinal, hepatic, cutaneous, renal and Received 8 October 2010; cardiovascular. A total of 42 389 serious ADR reports were identified, and 38 506 revised 27 June 2011; were included in a case/noncase analysis. Ketoprofen was associated with the highest ntal & accepted 11 August 2011 cumulative reported rate of serious ADRs (0.78 cases per million defined daily doses), e followed by diclofenac (0.58), nimesulide (0.52), naproxen (0.50), piroxicam (0.47), tenoxicam (0.42), meloxicam (0.41) and aceclofenac (0.30). The most frequently *Correspondence and reprints: maryse.lapeyre-mestre@ reported serious ADRs were cutaneous, followed by gastrointestinal, hepatic, renal univ-tlse3.fr and rarely, cardiovascular events. In the case/noncase analysis, ketoprofen, piroxicam and naproxen were associated with the highest risk of serious gastroin- testinal ADRs (odds ratios [ORs] of 6.87, 6.54 and 5.07, respectively). Nimesulide Fundam and aceclofenac were associated with the highest risk of liver ADRs (adjusted ORs of 4.53 and 3.67, respectively), as was meloxicam for cutaneous ADRs (adjusted OR of 3.15) and tenoxicam for renal ADRs (adjusted OR of 3.17). The most frequent serious ADRs reported with the selected oral NSAIDs are cutaneous, followed by gastro- intestinal, hepatic and renal events. The highest risks for serious gastrointestinal, hepatic, cutaneous and renal adverse events were linked, respectively, with ketoprofen, nimesulide, meloxicam and tenoxicam compared with the other NSAIDs. possess different chemical and clinical profiles but INTRODUCTION essentially exert the same therapeutic properties and Nonsteroidal anti-inflammatory drugs (NSAIDs) are are associated with similar adverse effects. Gastrointes- widely used to treat a large number of common acute tinal injuries, which range from dyspepsia to fatal upper and chronic inflammatory conditions. These drugs gastrointestinal tract bleeding and perforation, are ª 2011 The Authors Fundamental and Clinical Pharmacology ª 2011 Socie´ te´ Franc¸aise de Pharmacologie et de The´ rapeutique Fundamental & Clinical Pharmacology 27 (2013) 223–230 223 224 M. Lapeyre-Mestre et al. among the most common adverse drug reactions (ADRs) corticosteroids, aspirin or anticoagulants, serious com- associated with the use of NSAID [1–3]. Other important orbidity or a history of upper gastrointestinal events ADRs include skin reactions, renal complications, aller- [10]. gic reactions, alteration in hepatic enzyme levels and, The aim of this pharmacoepidemiological study was to rarely, hepatopathies [4–7]. Hepatic ADRs associated compare the safety profile of eight-first-generation NSA- with NSAIDs are quite uncommon when compared with IDs available in France, by assessing the reporting of other pharmacological classes such as antibiotics [6,8]. serious ADRs in several system organ classes [SOCs] from Epidemiological studies have reported the incidence of data in the French pharmacovigilance system from 2002 acute liver injury to be 1–9 cases per 100 000 NSAID to 2006. users [6,7]. As recommended by the European Medicine Agency METHODS (EMA) [9], NSAIDs should be prescribed at the lowest effective dose and for the shortest time necessary to This study analysed serious ADRs spontaneously re- control symptoms. Moreover, other factors such as the ported to the French pharmacovigilance system between overall safety profile of each compound (e.g. potential 1st January 2002 and 31st December 2006 for NSAIDs gastrointestinal and other concerns) and individual risk available in France. It has been compulsory since 1995 factors must be considered for improved patient man- for all prescribers in France to report any ADR defined as agement [10]. ‘serious’ and/or ‘unexpected’ [16]. ‘Serious’ ADRs are Differences in safety profiles between NSAIDs are a key defined as those being fatal, life-threatening, causing discriminator for choosing between one NSAID and hospitalization, resulting in persistent or significant another, and not all NSAIDs have the same level of risk disability or incapacity, requiring intervention to prevent for inducing gastrointestinal ADRs. First-generation permanent damage or causing a congenital anomaly NSAIDs are nonselective and block the activity of both [16]. This study focused on serious ADRs associated with COX-1 and COX-2. Second-generation agents, the COX-2 gastrointestinal, hepatic, cutaneous, renal and cardio- inhibitors, were developed with the aim of reducing the vascular systems. incidence of gastrointestinal adverse effects by sparing Serious ADRs of interest were identified from specific the gastrointestinal protective functions of COX-1 while codes of the World Health Organisation Adverse Reac- still inhibiting inflammation [11,12]. However, it was tions Terminology (WHO-ART) classification of selected clear reasonably soon after their commercialization that organ class disorders (Table I). the use of these COX-2 inhibitors (i.e. rofecoxib and valdecoxib) was associated with an increase in cardio- Study design vascular risk, leading to their withdrawal from the The data collected were analysed for the reporting of market [13,14]. These events led to a revision of the serious ADRs in the population treated with the selected overall safety profile of all NSAIDs, particularly in regard NSAIDs and to calculate the odd ratios (ORs) of the to their renal and cardiovascular risk profile. Moreover, association of these ADRs with the NSAIDs in this a number of studies evaluating the gastrointestinal population, using a case/noncase analysis. tolerability of COX-2 inhibitors did not demonstrate a For the estimation of ADR reporting, data were lower risk of upper or lower gastrointestinal events analysed and compared for eight oral formulations of [15,16]. NSAIDs: aceclofenac, diclofenac, ketoprofen, meloxicam, Several factors influence a patient’s risk of developing naproxen, nimesulide, piroxicam and tenoxicam. different ADRs while receiving NSAIDs; for example, Case/noncase analysis has been widely used in the elderly patients or those with cardiovascular disorders, last decade in several spontaneous reporting data- chronic renal disease, rheumatoid arthritis or chronic bases, including the French pharmacovigilance database obstructive pulmonary disease are at greater risk of [17,18]. For example, this analytical method was applied cardiovascular ADRs [15]. Gastrointestinal ADRs are to data from the French and Spanish pharmacovigilance important indicators when evaluating the overall risk national databases to compare the risk of hepatic profile of NSAIDs because of the risk of gastrointestinal damage with the administration of different NSAIDs bleeding and perforation. Risk factors for gastrointestinal [19]. In this method, ‘cases’ are the ADRs of interest and complications, according to the National Institute for the ‘noncase’ control group corresponds to all other Clinical Excellence, include age over 65 years, the use of ADRs recorded in the database. The principle is to ª 2011 The Authors Fundamental and Clinical Pharmacology ª 2011 Socie´ te´ Franc¸aise de Pharmacologie et de The´ rapeutique Fundamental & Clinical Pharmacology 27 (2013) 223–230 Adverse drug reactions related to oral NSAIDs’ use 225 Table I World health organisation adverse reactions terminology (WHO-ART) codes for selected system organ class (SOC) disorders. WHO-ART codes SOC disorder 0700 Liver and biliary system disorders (hepatic failure or necrosis, abnormal hepatic functions, hepatitis, cholestasis, increase in liver enzymes) 0600 Gastrointestinal system disorders (ulcer, gastritis, gastrointestinal haemorrhage, intestinal perforation…) 0100 Skin and appendages disorders (dermatitis, eruption, toxic epidermic necrosis, drug-related eruption, Lyell and Stevens–Johnson syndrome…) 1300 Urinary system disorders (nephritis, renal failure, decrease in renal clearance, tubular nephropathy…) 1020 Myo-, endo-, pericardial and valve disorders (angor, myocardial infarction, coronary thrombosis, coronary arteriosclerosis) 1040 Vascular (extracardiac) disorders (cerebral infarction, embolism; arterial, peripheral embolism/ischaemia; arterial, carotid, cerebral, upper limb thrombosis…) 1810 Body as a whole – general disorders (ischaemic necrosis)
Load more

Recommended publications
  • Nimesulide: Patients Still Exposed to a Risk of Severe Hepatitis
    Translated from Rev Prescrire January 2011; 31 (327): 22-23 Nimesulide: patients still exposed to a risk of severe hepatitis Abstract imesulide, a nonsteroidal anti- Severe liver damage at standard N inflammatory drug (NSAID), has doses, especially in young women. In Nimesulide, a nonsteroidal anti- been on the French market since 2007, the Italian Medicines Agency inflammatory drug (NSAID) that has 1998 (1). It is neither more effective nor released Italian pharmacovigilance data been marketed in France since 1998, is better tolerated than many other showing that hepatic adverse effects rep- neither more effective nor better tol- NSAIDs, and has been shown to cause resented 13.8% of reports implicating erated than other NSAIDs. potentially life-threatening liver da- nimesulide, compared to only 1.4% for mage (1-5). ibuprofen and 2.8% for diclofenac (3). Many reports and reviews published What is known concerning the hepatic The CHMP report published in 2008 by drug regulatory agencies in Spain, adverse effects of nimesulide in early included similar findings. Among the Ireland and Italy have warned of the 2011? 574 reports implicating nimesulide record- hepatic adverse effects of nimesulide. ed in the European EudraVigilance phar- In early 2008, 17 cases of nimesulide- An increasing number of reports of macovigilance database, the proportion of induced liver damage requiring trans- liver damage. Soon after it was first mar- hepatic disorders (cholestasis, jaundice, plantation had been reported in Ire- keted, cases of hepatitis were attributed liver failure, and hepatitis) was higher land, Italy, Spain, Finland and France. to nimesulide, including a case of fulmi- than with cox-2 inhibitors.
    [Show full text]
  • White Paper on Nimesulide Pharmacologic Category
    White paper on Nimesulide Pharmacologic Category : Analgesic, Nonsteroidal Anti-inflammatory Drug; Nonsteroidal Anti-inflammatory Drug (NSAID) Indications: Fever, Pain & Inflammation Duration: Can be safely prescribed upto 15 days. Adults: Oral: 100 mg twice daily. Children below 12 years: Not to be used. Product Availability: Product available in various countries; not currently available in the U.S. Dosage Forms: Tablet: 100 mg 1. Nimesulide has preferential selectivity for COX-2 over COX-1 in vivo at full therapeutic doses and induces less gastrointestinal damage than that seen with naproxen in the short term. [ Uptodate: Gut. 2001;48(3):339.] 2. Atopy is a risk factor for non-steroidal anti-inflammatory drug sensitivity. The prevalence of atopy is increased in challenge-proven NSAID-intolerant patients. The atopic condition may represent an important risk factor for developing reactions to these drugs. Paracetamol and nimesulide are relatively safe alternative choices in those patients. [ Uptodate: Ann Allergy Asthma Immunol. 2000;84(1):101.] 3. Topical NSAIDs that are effective for chronic musculoskeletal pain in adults include diclofenac, ketoprofen (level 1 [likely reliable] evidence), ibuprofen, felbinac, and nimesulide (level 2 [mid-level] evidence) [DynaMed] 4. nimesulide may be associated with better efficacy than diclofenac for acute gout (level 2 [mid-level] evidence) [Ter Arkh 2007;79(5):35 ] 5. Nimesulide is safe in Crohn's disease [DynaMed: Clin Gastroenterol Hepatol 2006 Feb;4(2):196] 6. It is safe in ulcerative colitis { DynaMed Clin Gastroenterol Hepatol 2006 Feb;4(2):196, commentary can be found in Clin Gastroenterol Hepatol 2006 Feb;4(2):157] 7. Many PUBMED studies are available about its efficacy in primary dysmennhorea, acute dental pain, respiratory inflammatory conditions etc.
    [Show full text]
  • Aceclofenac As a Potential Threat to Critically Endangered Vultures in India: a Review Author(S): Pradeep Sharma Source: Journal of Raptor Research, 46(3):314-318
    Aceclofenac as a Potential Threat to Critically Endangered Vultures in India: A Review Author(s): Pradeep Sharma Source: Journal of Raptor Research, 46(3):314-318. 2012. Published By: The Raptor Research Foundation DOI: http://dx.doi.org/10.3356/JRR-11-66.1 URL: http://www.bioone.org/doi/full/10.3356/JRR-11-66.1 BioOne (www.bioone.org) is a nonprofit, online aggregation of core research in the biological, ecological, and environmental sciences. BioOne provides a sustainable online platform for over 170 journals and books published by nonprofit societies, associations, museums, institutions, and presses. Your use of this PDF, the BioOne Web site, and all posted and associated content indicates your acceptance of BioOne’s Terms of Use, available at www.bioone.org/ page/terms_of_use. Usage of BioOne content is strictly limited to personal, educational, and non- commercial use. Commercial inquiries or rights and permissions requests should be directed to the individual publisher as copyright holder. BioOne sees sustainable scholarly publishing as an inherently collaborative enterprise connecting authors, nonprofit publishers, academic institutions, research libraries, and research funders in the common goal of maximizing access to critical research. SHORT COMMUNICATIONS J. Raptor Res. 46(3):314–318 E 2012 The Raptor Research Foundation, Inc. ACECLOFENAC AS A POTENTIAL THREAT TO CRITICALLY ENDANGERED VULTURES IN INDIA:AREVIEW PRADEEP SHARMA1 Department of Veterinary Microbiology and Biotechnology, Rajasthan University of Veterinary and Animal Science, Bikaner 334001, Rajasthan, India KEY WORDS: Vultures; Gyps; aceclofenac; diclofenac; India; cations in humans (Kay and Alldred 2003) and marked South Asia; toxicity. analgesic, antiarthritic and antipyretic properties.
    [Show full text]
  • Rationale of Aceclofenac in Management of Pyrexia in Paediatric Practice
    ISSN: 2574-1241 Volume 5- Issue 4: 2018 DOI: 10.26717/BJSTR.2018.11.002112 Avinash Shankar. Biomed J Sci & Tech Res Research Article Open Access Rationale of Aceclofenac in Management of Pyrexia in Paediatric Practice Avinash Shankar*1, Amresh Shankar2 and Anuradha Shankar3 1Postgraduate in Endocrinology & Metabolism (AIIMS Delhi), Chairman National Institute of Health & Research Warisaliganj (Nawada), India 2Aarogyam Punarjeevan Ram Bhawan, India 3Centre for Indigenous Medicine & Research Senior Research Fellow Regional Institute of Ayurveda, India Received: : November 19, 2018; Published: : November 28, 2018 *Corresponding author: Avinash Shankar, Postgraduate in Endocrinology & Metabolism (AIIMS Delhi) Chairman National Institute of Health & Research Warisaliganj (Nawada) Bihar, India Abstract Pyrexia, a complex physiological response triggered by infection or aseptic stimuli causes increase in Prostaglandin E2(PGE2)concentration children with pyrexia of varied origin and to calm the temperature at optimal level various therapeutics are in vogue but attendance of children with antipyreticsin brain and adversity later firing presenting rate of neuronesas morbidity of thermoregulatoryand mortality necessiated centre i.e.an evaluationHypothalamus. of presenting Majority hazardsattendance with at consuming paediatrician antipyretics. chamber are of Objective of Study: Analyse the rationality of Aceclofenac paracetamol combination, as antipyretics in paediatric practice. Material & Methods: Analysis of datasheet of patients admitted with antipyretics adversity at Centre For Children Disease & Research. Result: Children consuming Aceclofenac Sodium Paracetamol presented with grave status of prolonged hypothermia, CNS disturbances like Dizziness, Convulsion, coma in addition to more pronounced other presentation like persistant vomiting, haematemesis, blood dyscariasis, rash, albuminuria than other. Conclusion: Acceclofenac sodium Paracetamol combination must be restricted for paediatrics use considering its dreaded outcome.
    [Show full text]
  • Comparison of Efficacy of Diclofenac Versus Aceclofenac
    The Internet Journal of Orthopedic Surgery ISPUB.COM Volume 19 Number 2 Comparison of Efficacy of Diclofenac versus Aceclofenac in Post Operative Pain in Lower limb fractures: a Double blind, Randomized Study V Sharma, B Awasthi, S Rana, S Sharma Citation V Sharma, B Awasthi, S Rana, S Sharma. Comparison of Efficacy of Diclofenac versus Aceclofenac in Post Operative Pain in Lower limb fractures: a Double blind, Randomized Study. The Internet Journal of Orthopedic Surgery. 2012 Volume 19 Number 2. Abstract INTRODUCTION: Providing effective postoperative analgesia is a significant challenge in patients undergoing orthopedic surgery. Non steroidal anti-inflammatory group of drugs is used mostly to achieve it. This clinical study was done to investigate efficacy of Injectable Aceclofenac over inj. Diclofenac in patients with severe postoperative pain in lower limb fractures. METHODS: 100 patients (aged 18-60 yr) of lower limb fractures were enrolled as per inclusion criteria . They were randomly assigned to Group A or Group B (50 patients each ) .Severe pain was postoperative pain 7 or >7 on Numerical Rating Scale. For postoperative analgesia, in Group A Inj. Aceclofenac ( 12 hourly) and in Group B Inj. Diclofenac (8 hourly) was given . To abort pain in case of no relief Inj. Tramadol was given. Decrease in Numerical Rating Scale score in either the group and associated adverse effects were noted . Patients’ overall subjective response to therapy was rated as poor , fair , good or excellent . RESULTS: After treatment at 10 min. only the mean pain score had 47.8% fall in Group A and 40.3% in Group B.
    [Show full text]
  • Effects of the European Restrictive Actions Concerning Nimesulide Prescription
    ANN IST SUPER SANITÀ 2010 | VOL. 46, NO. 2: 153-157 153 DOI: 10.4415/ANN_10_02_08 ES Effects of the European restrictive actions I concerning nimesulide prescription: a simulation study on hepatopathies ETHODOLOG M and gastrointestinal bleedings in Italy ND A Mauro Venegoni(a), Roberto Da Cas(b), Francesca Menniti-Ippolito(b) and Giuseppe Traversa(b) RCH A (a)Centro Regionale di Farmacovigilanza, Regione Lombardia, Milan, Italy (b) ESE Centro Nazionale di Epidemiologia, Sorveglianza e Promozione della Salute, R Istituto Superiore di Sanità, Rome, Italy Summary. In 2002 and 2007 the European Medicines Agency (EMA) examined the signals of a greater risk of hepatopathies related to nimesulide use. In 2007 restrictive actions were adopted in Europe. Moreover, EMA initiated a new referral in February 2010. The objective of this paper is to evaluate the effects of the 2007 regulatory measures concerning nimesulide and to estimate the potential effect of further actions. Specifically, we carried out a simulation on the expected number of hospitalisations for hepatopathies and upper gastrointestinal bleedings (UGIBs) in Italy before and after the regulatory measures (2006 vs. 2009), taking into account the shifting of nimesulide prescriptions on other non steroidal anti-inflammatory drugs (NSAIDs). The expected figures of hospitalisation for hepatopathies and UGIBs for all NSAIDs were calculated on the basis of risk estimates reported in two epidemiological studies. The result of the simulation suggests that the im- plementation of the restrictive actions might prevent 79 events of liver injuries, but might increase UGIBs by 859 events. The simulation helped to clarify the effects on hepatopathies and UGIBs as a consequence of nimesulide restriction of use.
    [Show full text]
  • S1 Table. List of Medications Analyzed in Present Study Drug
    S1 Table. List of medications analyzed in present study Drug class Drugs Propofol, ketamine, etomidate, Barbiturate (1) (thiopental) Benzodiazepines (28) (midazolam, lorazepam, clonazepam, diazepam, chlordiazepoxide, oxazepam, potassium Sedatives clorazepate, bromazepam, clobazam, alprazolam, pinazepam, (32 drugs) nordazepam, fludiazepam, ethyl loflazepate, etizolam, clotiazepam, tofisopam, flurazepam, flunitrazepam, estazolam, triazolam, lormetazepam, temazepam, brotizolam, quazepam, loprazolam, zopiclone, zolpidem) Fentanyl, alfentanil, sufentanil, remifentanil, morphine, Opioid analgesics hydromorphone, nicomorphine, oxycodone, tramadol, (10 drugs) pethidine Acetaminophen, Non-steroidal anti-inflammatory drugs (36) (celecoxib, polmacoxib, etoricoxib, nimesulide, aceclofenac, acemetacin, amfenac, cinnoxicam, dexibuprofen, diclofenac, emorfazone, Non-opioid analgesics etodolac, fenoprofen, flufenamic acid, flurbiprofen, ibuprofen, (44 drugs) ketoprofen, ketorolac, lornoxicam, loxoprofen, mefenamiate, meloxicam, nabumetone, naproxen, oxaprozin, piroxicam, pranoprofen, proglumetacin, sulindac, talniflumate, tenoxicam, tiaprofenic acid, zaltoprofen, morniflumate, pelubiprofen, indomethacin), Anticonvulsants (7) (gabapentin, pregabalin, lamotrigine, levetiracetam, carbamazepine, valproic acid, lacosamide) Vecuronium, rocuronium bromide, cisatracurium, atracurium, Neuromuscular hexafluronium, pipecuronium bromide, doxacurium chloride, blocking agents fazadinium bromide, mivacurium chloride, (12 drugs) pancuronium, gallamine, succinylcholine
    [Show full text]
  • Anti-Proliferative Effects of Piroxicam and Nimesulide on A431 Human
    Int J Cancer Manag. 2017 April; 10(4):e7565. doi: 10.5812/ijcm.7565. Published online 2017 April 22. Research Article Anti-Proliferative Effects of Piroxicam and Nimesulide on A431 Human Squamous Carcinoma Cell Line Faezeh Khodaie,1 Yalda Khazaei-Poul,1 and Taraneh Moini-Zanjani1,* 1Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, IR Iran *Corresponding author: Taraneh Moini-Zanjani, Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Koodakyar Street, Daneshjoo boulevard, Velenjak, Tehran, IR Iran. Tel/Fax: +98-21-22439969, Tel: +98-9123497094, E-mail: [email protected] Received 2016 June 15; Accepted 2017 March 08. Abstract Background: Skin cancer is one of the most common types of cancer worldwide and non-steroidal anti-inflammatory drugs (NSAIDs) have been proposed for prevention and treatment of a variety of cancers. Objectives: In this study we aimed to evaluate the cytotoxic effects of piroxicam (a non-selective cyclooxygenase (COX) inhibitor) and nimesulide (a highly selective COX-2 inhibitor) on A431 human squamous carcinoma cell line. Methods: Squamous carcinoma cell line (A431) was cultured in RPMI medium containing 10% FBS and penicillin-streptomycin at 37°C and 5% CO2. Cells were treated with different concentrations of piroxicam and nimesulide (100 - 1000 µmol/L) for 24, 48 and 72 hours (h). Anti-proliferative effects were determined using MTT colorimetric assay. Results: Piroxicam and nimesulide reduced cell viability in a time and concentration dependent manner. The most cytotoxic effect was produced in 72 hours incubation time. The IC50 value of nimesulide was significantly lower than piroxicam in 24 and 72 hours, but not in 48 hours treatment duration.
    [Show full text]
  • Indomethacin in Pregnancy: Applications and Safety
    Original Article 175 Indomethacin in Pregnancy: Applications and Safety Gael Abou-Ghannam, M.D. 1 Ihab M. Usta, M.D. 1 Anwar H. Nassar, M.D. 1 1 Department of Obstetrics and Gynecology, American University of Address for correspondence and reprint requests Anwar H. Nassar, Beirut Medical Center, Hamra, Beirut, Lebanon M.D., American University of Beirut Medical Center, P.O. Box 113-6044/B36, Hamra 110 32090, Beirut, Lebanon (e-mail: [email protected]). Am J Perinatol 2012;29:175–186. Abstract Preterm labor (PTL) is a major cause of neonatal morbidity and mortality worldwide. Among the available tocolytics, indomethacin, a prostaglandin synthetase inhibitor, has been in use since the 1970s. Recent studies have suggested that prostaglandin synthetase inhibitors are superior to other tocolytics in delaying delivery for 48 hours and 7 days. However, increased neonatal complications including oligohydramnios, Keywords renal failure, necrotizing enterocolitis, intraventricular hemorrhage, and closure of the ► indomethacin patent ductus arteriosus have been reported with the use of indomethacin. Indometh- ► tocolysis acin has been also used in women with short cervices as well as in those with idiopathic ► preterm labor polyhydramnios. This article describes the mechanism of action of indomethacin and its ► short cervix clinical applications as a tocolytic agent in women with PTL and cerclage and its use in ► polyhydramnios the context of polyhydramnios. The fetal and neonatal side effects of this drug are also ► fetal side effects summarized and guidelines for its use are proposed. Preterm labor (PTL) is a major cause of neonatal morbidity in women with PTL and cerclage and its use in the context of and mortality worldwide.1 Care of premature infants has polyhydramnios.
    [Show full text]
  • The Importance of COX-2 Inhibition for Aspirin Induced Asthma
    S54 Thorax 2000;55 (Suppl 2):S54–S56 Thorax: first published as 10.1136/thorax.55.suppl_2.S54 on 1 October 2000. Downloaded from The importance of COX-2 inhibition for aspirin induced asthma Alan Bennett There have been recent reviews of aspirin “specific” is used here to denote that the activ- induced asthma (AIA),12 the use of the ity is (usually) much greater against COX-2 COX-2 preferential inhibitor nimesulide in than against COX-1. Two drugs with a asthmatic patients intolerant to non-steroidal “preferential” status are nimesulide and mel- anti-inflammatory drugs (NSAIDs),3 and of oxicam, whereas two drugs that probably nimesulide in general.45 This paper discusses deserve the title “specific” are rofecoxib and the importance of inhibiting prostaglandin E2 celecoxib. (PGE2) synthesis in AIA, and the relative Nimesulide (4-nitro-2-phenoxymethane- safety of NSAIDs that preferentially inhibit sulphonanilide) is particularly important in COX-2. AIA because several studies have shown that it Aspirin and other NSAIDs cause broncho- is tolerated by most patients with the disorder constriction in about 10% of asthmatic to about the same extent as paracetamol. This subjects but NSAIDs relieve asthma in about sulphonanilide NSAID, which is eVective in 0.3%.2 This variability helps to show the com- treating a wide spectrum of inflammatory and plexity of the problem. Prostaglandins in painful conditions,7 was first marketed in 1985 human lung are formed by various tissues and and 10 years later it was found to be a cells, including bronchial muscle, epithelium, preferential inhibitor of COX-2.89Because it is and inflammatory cells,12 so the inhibition of not marketed in the USA, Japan, or the UK, prostaglandin formation can have numerous nimesulide is not well known in some parts of eVects.
    [Show full text]
  • Nimesulide for Painful Osteoarthritis
    For reprint orders, please contact: DRUG EVALUATION [email protected] Nimesulide for painful osteoarthritis Mauro Bianchi Osteoarthritis is one of the most common joint disorders in the world. It is costly and a major University of Milan, School of cause of pain and disability, especially in the elderly. The severity of pain often calls for Medicine, Department of Pharmacology, Via Vanvitelli, treatment with nonsteroidal anti-inflammatory drugs. Worldwide experience with nimesulide 32, 20129 Milano, Italy shows that this nonsteroidal anti-inflammatory drug has a number of pharmacological Tel.: +39 025 031 6930; properties that may make it favorable in the treatment of joint diseases. In recent years, Fax: +39 025 031 6949; several controlled studies have been carried out in order to investigate its analgesic effects in [email protected] patients with OA. The objective of this article is to review some of the features of osteoarthritis and to identify the role of nimesulide as a drug particularly tailored for the treatment of painful osteoarthritis. Osteoarthritis (OA) is one of the most common Rheumatism (EULAR) [4] and the American Col- forms of musculoskeletal disorder encountered lege of Rheumatology (ACR) Recommendations worldwide, particularly in Western populations. [11]. However, the severity of pain often requires A recent WHO report on the global burden of treatment with nonsteroidal antiinflammatory disease indicates that OA is likely to become one drugs (NSAIDs), which are the drugs preferred by of the most important causes of disability in many patients with OA [12]. Indeed, NSAIDs are both women and men [1]. The prevalence of OA the drug most commonly used by many doctors increases with age, affecting a large proportion of for the management of pain in OA patients, in elderly people [2].
    [Show full text]
  • Celofen® Aceclofenac
    Only for the use of Medical Professionals Celofen® Aceclofenac Presentation Celofen® 100mg Tablets: Round, light pink colored film coated tablet, one side embossed with 'ACI' and other side with a break line. Each tablet contains 100mg Aceclofenac BP. Description Celofen® is a non-steroidal agent with anti-inflammatory and analgesic properties. Its mechanism of action is largely based on inhibition of prostaglandin synthesis. Celofen® is a potent inhibitor of the enzyme cyclooxygenase, which is involved in the production of prostaglandins. Indications & uses Celofen® is indicated in relieving pain and inflammation in osteoarthritis, rheumatoid arthritis and ankylosing spondylitis. Dosage & administration Adults: The maximum recommended dose is 200mg daily, taken as two separate 100mg doses, one tablet in the morning and one in the evening. Children: There is no clinical data on the use of Aceclofenac in children. Elderly: The pharmacokinetics of Aceclofenac are not altered in elderly patients, therefore it is not considered necessary to modify the dose and dose frequency. Renal insufficiency: There is no evidence that the dosage of Aceclofenac needs to be modified in patients with mild renal impairment. Hepatic insufficiency: The dose of Aceclofenac should be reduced in patients with hepatic impairment. An initial daily dose of 100mg should be administered. Contraindications, warnings, etc. Contraindications: Aceclofenac is contraindicated in patients previously sensitive to Aceclofenac or aspirin or other NSAIDs. It should not be administered to patients with active or suspected peptic ulcer or gastrointestinal bleeding and moderate to severe renal impairment. Precautions: Aceclofenac should be administered with caution to patients with symptoms indicative of gastrointestinal disorders, with a history of peptic ulceration, ulcerative colitis, Crohn's disease, hepatic porphyria, and coagulation disorders.
    [Show full text]