DOCSLIB.ORG

Esomeprazole: a New Proton Pump Inhibitor for NSAID-Associated Peptic Ulcers and Dyspepsia

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Esomeprazole: a New Proton Pump Inhibitor for NSAID-Associated Peptic Ulcers and Dyspepsia DRUG PROFILE Esomeprazole: a new proton pump inhibitor for NSAID-associated peptic ulcers and dyspepsia Grace Lai-Hung Wong Ulcer and ulcer symptoms related to the use of non-steroidal anti-inflammatory drugs & Joseph JY Sung† (NSAIDs) and aspirin constitute a major global health issue. Despite various attempts to †Author for correspondence prevent and heal injuries inflicted by NSAIDs and aspirin, acid suppression remains one of The Prince of Wales Hospital, Department of Medicine and the cornerstones in the management of NSAID-associated ulcers. Esomeprazole, the Therapeutics, 9/F, S-optical isomer (enantiomer) of omeprazole, suppresses gastric acid secretion by 30–32 Ngan Shing Road, inhibiting the parietal cell membrane enzyme H+/K+-ATPase. With improved bioavailability, Shatin, NT, Hong Kong SAR due to reduced first-pass metabolism in the liver, esomeprazole promises to be more Tel.: +852 2632 3132 potent in acid suppression in the stomach. Similar to omeprazole, the safety profile of Fax: +852 2645 1699 esomeprazole has been well established. Clinical studies comparing esomeprazole with [email protected] other proton pump inhibitors (PPIs) in the healing of NSAID-related ulcer are few. Recent multicenter randomized studies demonstrated that esomeprazole significantly improves dyspeptic symptoms in patients taking nonselective NSAIDs and specific cyclooxygenase-2 inhibitors. Esomeprazole also protects the stomach from aspirin-induced ulcer bleeding. Safety profiles of esomeprazole appear promising. Non-steroidal anti-inflammatory drugs both basal and stimulated acid secretion. PPIs are (NSAIDs) are the most commonly used medica- most effective against meal-induced gastric acid tions for chronic pain and arthritis due to their secretion [3]. Omeprazole, the first drug in this efficacy in pain control. However, it is well rec- class, was introduced in 1988. Since then, three ognized that NSAIDs cause various gastrointes- other PPIs have been introduced: lansoprazole tinal (GI) conditions including dyspepsia, (1995), rabeprazole (1999) and pantoprazole peptic ulcer disease and its complications (2000). In 2001, esomeprazole was introduced as (bleeding and perforation), and small bowel the S-optical isomer of the racemic molecule of stricture. These complications have a huge omeprazole. All PPIs share a common structural impact on healthcare system around the world. motif but vary in their substitutions. PPIs have In the USA alone, the use of NSAIDs causes revolutionized the management of acute upper more than 100,000 hospitalizations and 17,000 gastrointestinal bleeding (GIB), as adequate acid deaths annually [1]. The risk is substantially suppression improves the success of endoscopic higher among the elderly population and those hemostasis, and reduces the need of surgery [4]. with concomitant medical illnesses. This article focuses on the existing literature of As mucosal injury induced by NSAIDs is an esomeprazole and it’s effects in preventing and acid-dependent process, effective acid suppres- healing of NSAID-induced GI mucosal injury. sion is one of the ways to prevent NSAID-associ- ated ulcer formation and complications. Proton Chemistry pump inhibitors (PPIs) are a group of acid-sup- Omeprazole is a racemate with a sulfur atom pressing agents that act by binding covalently to which acts as a chiral center for the compound. Keywords: aspirin, duodenal the amino acid cysteine 813 residue present at It contains two optical isomers, S- and R-ome- ulcer, esomeprazole, gastric their primary binding site on the H+/K+-ATPase, prazole. Conversion of the two enantiomers to ulcer, gastrointestinal also known as the ‘proton pump’, on the luminal the active form, the achiral sulfenamide, occurs bleeding, Helicobacter pylori, histamine-2 receptor surface of gastric parietal cells [2]. This results in via an acid-dependent chemical reaction at the antagonists, NSAID, peptic irreversible inhibition of acid secretion by the gas- luminal surface of the parietal cells and at the ulcer disease, proton pump tric H+/K+-ATPase. Only after recruiting newly same rate for both enantiomers. inhibitors synthesized proton pump molecules from the Esomeprazole is the S-isomer (enantiomer) of Golgi apparatus of the cell will acid secretion omeprazole, and the first PPI to be developed as gradually resume [3]. As PPIs block the final step an optical isomer. Similar to other PPIs, esome- in the pathway to gastric acid secretion arising prazole suppresses gastric acid secretion by inhib- Future Drugs Ltd from various stimuli, they are effective against iting the parietal cell membrane enzyme 10.1586/14750708.3.2.227 © 2006 Future Drugs Ltd ISSN 1475-0708 Therapy (2006) 3(2), 227–236 227 DRUG PROFILE – Wong & Sung Figure 1. Molecular structure of omepraozle: (S)-5-methoxy-2-([(4-methoxy-3,5- dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole and its two optical isomers, the S-isomer (esomeprazole) and the R-isomer of omeprazole. CH3O H3C CH3 N N S O N CH3O Omeprazole S-isomer R-isomer CH3O CH3O H3C CH3 H3C CH3 N N N S N S O O NH NH CH3O CH3O Esomeprazole H+/K+-ATPase. Esomeprazole is rapidly sulfenamide analog, in the acidic environment of degraded in acidic media but is stable under the gastric parietal cell. It effectively blocks acid alkaline conditions just as all other PPIs are. secretion by irreversibly binding to and inhibit- Each capsule of esomeprazole magnesium con- ing the enzyme H+/K+-ATPase that resides on tains enteric-coated granules to prevent the luminal surface of the parietal cell mem- esomeprazole degradation by gastric acidity. brane, resulting in disulfide bond formation Esomeprazole, chemical name: (S)-5-meth- with cysteine 813 located within the α-subunit oxy-2-([(4-methoxy-3,5-dimethyl-2-pyridinyl) of the enzyme (Figure 2). This is the residue that is methyl]sulfinyl)-1H-benzimidazole, (Figure 1) is intimately involved in H+ transport. All PPIs are a weak base. It is converted to its active form, a weak protonatable pyridines, with a pKa 4.0 for 228 Therapy (2006) 3(2) Esomeprazole – DRUG PROFILE Figure 2. Rearrangement of esomeprazole. OCH3 OCH3 OCH3 H3C CH3 H3C CH3 H3C CH3 H+ N N H+/K+- ATPase N Slow S Cys813 S H S O N N N N N S N OCH OCH3 3 OCH3 Esomeprazole Sulfenamide analog Esomeprazole rearranges (in the presence of acid) to a sulfenamide analog, which irreversibly binds to and inhibits the enzyme H+/K+- ATPase that resides on the luminal surface of the parietal cell membrane, resulting in disulfide bond formation with cysteine 813 located within the α-subunit of the enzyme. omeprazole, esomeprazole and lansoprazole, 3.9 by both CYP2C19 (73%) and CYP3A4 (27%). for pantoprazole and 5.0 for rabeprazole. The rate As a result of this difference in liver metabo- of conversion varies among the compounds and is lism of the drug, intrinsic clearance of R-iso- inversely proportional to their pKa: that is, mer is three times faster than the S-isomer, rabeprazole > omeprazole/esomeprazole = lansop- hence a higher plasma concentration of the razole > pantoprazole. As a result, they accumulate later. In contrast, esomeprazole has reduced specifically and selectively in the secretory canalic- first-pass metabolism and slower clearance. ulus, the highly acidic space, of the parietal cell [3]. Pharmacokinetic studies show that esome- Within that space, PPIs undergo an acid catalyzed prazole has a significantly higher area under conversion to become a reactive species, the curve (AUC) value and longer half-life than thiophilic sulfenamide, which are permanent both the R-isomer and racemic omeprazole, cations. resulting in a 10–20% increase in the acid-sup- pressing effect of the drug [6]. The half-life of Pharmacology elimination is 1–1.5 h, and the time to reach Esomeprazole has a different pharmacody- peak plasma drug level after oral administration namic and pharmacokinetic profile from its is 1.5 h. Although altered P450 metabolism parent compound, omeprazole. It is designed appears beneficial as it achieves a higher plasma to improve bioavailability of the drug with levels of esomeprazole, when the CYP2C19 more consistent pharmacokinetics and hence pathway becomes saturated, the isoenzyme may better acid control. After ingestion, both the S- become a major target for interactions with and R-isomers of omeprazole are absorbed other drugs, including warfarin, diazepam and through the intestine and passed through the phenytoin. CYP3A4-mediated metabolism may liver (first-pass metabolism) and transformed also be activated under such conditions and into the active compound which is delivered hence become the principal route of drug elim- back to the stomach as two inactive metabo- ination. Furthermore, induction of CYP450A, lites, the 5-hydroxy and sulfone forms of the another P450 isoenzyme, may occur in compounds [5]. Unlike the R-isomer which is CYP2C19-deficient or saturated individuals, predominantly metabolized by CYP2C19 making them susceptible to interference with (98%), S-isomer (esomeprazole) is metabolized theophylline metabolism [5]. www.future-drugs.com 229 DRUG PROFILE – Wong & Sung Absorption of esomeprazole is decreased by 40 mg was significantly more effective than lan- 43–53% when taken with food. As the amount soprazole 30 mg for controlling intragastric of H+/K+-ATPase present in the parietal cell is acidity, with a difference in percentage of time greatest after prolonged fasting, PPIs are best where gastric pH was above 4 of 5.5% (95% administered before meals. In most individuals, confidence interval
Load more

Recommended publications
  • Nexium Control, Esomeprazole
    27 June 2013 EMA/498929/2013 Committee for Medicinal Products for Human Use (CHMP) Assessment report Nexium Control International non-proprietary name: esomeprazole Procedure No. EMEA/H/C/002618 Note Assessment report as adopted by the CHMP with all information of a commercially confidential nature deleted. 7 Westferry Circus ● Canary Wharf ● London E14 4HB ● United Kingdom Telephone +44 (0)20 7418 8400 Facsimile +44 (0)20 7418 8613 E -mail [email protected] Website www.ema.europa.eu An agency of the European Union © European Medicines Agency, 2013. Reproduction is authorised provided the source is acknowledged. Product information Marketing authorisation application Name of the medicinal product: Nexium Control Applicant: AstraZeneca AB Building 411A, Floor 4 S - 151 85 Södertälje SWEDEN Active substance: esomeprazole (as magnesium trihydrate) International Nonproprietary Name/Common Name: esomeprazole Pharmaco-therapeutic group Proton pump inhibitors (ATC Code): (A02BC05) Therapeutic indication: Nexium Control is indicated for the short-term treatment of reflux symptoms (e.g. heartburn and acid regurgitation) in adults. Pharmaceutical form: Gastro-resistant tablet Strength: 20 mg Route of administration: Oral use Packaging: blister (PVC/PVDC) Package sizes: 7 tablets and 14 tablets Assessment report EMA/498929/2013 Page 2/70 Table of contents 1. Background information on the procedure .............................................. 6 1.1. Submission of the dossier .....................................................................................
    [Show full text]
  • Dr. Reddy's – Recall of Ranitidine
    Dr. Reddy’s – Recall of ranitidine • On October 23, 2019, Dr. Reddy’s announced the voluntary, consumer-level recall of prescription ranitidine due to potential contamination with N-nitrosodimethylamine (NDMA). • Dr. Reddy’s initially announced retail level recalls for prescription and OTC ranitidine in early October; however, the recall of prescription ranitidine products has been escalated to the consumer level. The recall of OTC ranitidine remains at the retail level. Prescription Ranitidine Capsules Recalled by Dr. Reddy’s Product Description NDC# Ranitidine 150 mg capsules, 60 count bottle 55111-129-60 Ranitidine 150 mg capsules, 500 count bottle 55111-129-05 Ranitidine 300 mg capsules, 30 count bottle 55111-130-30 Ranitidine 300 mg capsules, 100 count bottle 55111-130-01 • Refer to the Dr. Reddy’s announcement for a complete list of the OTC recalled ranitidine products. • Other manufacturers, including Apotex, Perrigo and Sanofi have recently announced retail level recalls of their OTC ranitidine products. • In September, Sandoz issued a consumer level recall of prescription ranitidine products. • These recalls follow a recent FDA statement about NDMA impurities detected in ranitidine medicines. • NDMA is classified as a probable human carcinogen based on results from laboratory tests. NDMA is a known environmental contaminant and found in water and foods, including meats, dairy products, and vegetables. • Ranitidine is an OTC and prescription drug. Ranitidine is an H2 (histamine-2) blocker, which decreases the amount of acid created by the stomach. OTC ranitidine is approved to prevent and relieve heartburn associated with acid ingestion and sour stomach. • Prescription ranitidine is approved for multiple indications, including treatment and prevention of ulcers of the stomach and intestines and treatment of gastroesophageal reflux disease.
    [Show full text]
  • Label Phase of the Study
    HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include all the information needed to use ------------------------WARNINGS AND PRECAUTIONS----------------­ NEXIUM safely and effectively. See full prescribing information for • Symptomatic response does not preclude the presence of gastric NEXIUM. malignancy (5.1) • Atrophic gastritis has been noted with long-term omeprazole therapy NEXIUM (esomeprazole magnesium) Delayed-Release Capsules, for Oral (5.2) Use • PPI therapy may be associated with increased risk of Clostridium NEXIUM (esomeprazole magnesium) For Delayed-Release Oral difficile associated diarrhea. (5.3) Suspension • Bone Fracture: Long-term and multiple daily dose PPI therapy may be Initial U.S. Approval: 1989 (omeprazole) associated with an increased risk for osteoporosis-related fractures of the hip, wrist or spine. (5.4) -----------------------RECENT MAJOR CHANGES-----------------------­ • Hypomagnesemia has been reported rarely with prolonged treatment Warnings and Precautions, Clostridium difficile associated 09/2012 with PPIs (5.5) diarrhea (5.3) • Avoid concomitant use of NEXIUM with St John’s Wort or rifampin Warnings and Precautions, Concomitant use of NEXIUM with due to the potential reduction in esomeprazole levels (5.6) (7.3) Methotrexate (5.10) 01/2012 • Interactions with diagnostic investigations for Neuroendocrine Tumors: Increases in intragastric pH may result in hypergastrinemia and -----------------------INDICATIONS AND USAGE-----------------------­ enterochromaffin-like cell hyperplasia and
    [Show full text]
  • Proton Pump Inhibitors Aciphex
    PHARMACY PRE-AUTHORIZATION CRITERIA DRUG (S) Proton Pump Inhibitors Aciphex (Brand name) Dexilant Nexium/esomeprazole (RX Version) Omeprazole-bicarbonate Prevacid (Brand name) Prilosec (Brand name) Protonix (Brand name) Zegerid (RX Version and Brand name) POLICY # 14157 INDICATIONS These agents are approved for the treatment of duodenal ulcers, gastroesophageal reflux disease (GERD), Zollinger Ellison syndrome and H. pylori eradication. CRITERIA DRUG FREEDOM DRUG LIST Step COMMERCIAL DRUG LIST Step Requirements Requirements Aciphex (brand All of these: All of these: name) • Nexium OTC • Nexium OTC • Prilosec OTC , omeprazole, • Prilosec OTC , omeprazole, or Zegerid OTC or Zegerid OTC • Prevacid 24HR OTC/ • Prevacid 24HR OTC/ lansoprazole lansoprazole • Protonix/pantoprazole • Protonix/pantoprazole Dexilant All of these: ALL of these: • Nexium OTC • Nexium OTC • Prilosec OTC , omeprazole, • Prilosec OTC , omeprazole, or Zegerid OTC or Zegerid OTC • Prevacid 24HR OTC/ • Prevacid 24HR OTC/ lansoprazole lansoprazole • Protonix/pantoprazole • Protonix/pantoprazole esomeprazole All of these: All of these: • Nexium OTC • Nexium OTC • Prilosec OTC , omeprazole, • Prilosec OTC , omeprazole, or Zegerid OTC or Zegerid OTC • Prevacid 24HR OTC/ • Prevacid 24HR OTC/ PHARMACY PRE-AUTHORIZATION CRITERIA lansoprazole lansoprazole • Protonix/pantoprazole • Protonix/pantoprazole lansoprazole PA Not Required PA Not Required Nexium (RX All of these: All of these: Version) • Nexium OTC • Nexium OTC • Prilosec OTC , omeprazole, • Prilosec OTC , omeprazole, or
    [Show full text]
  • PHRP March 2015
    March 2015; Vol. 25(2):e2521518 doi: http://dx.doi.org/10.17061/phrp2521518 www.phrp.com.au Research Manual versus automated coding of free-text self-reported medication data in the 45 and Up Study: a validation study Danijela Gnjidica,b,i, Sallie-Anne Pearsona,c, Sarah N Hilmerb,d, Jim Basilakise, Andrea L Schaffera, Fiona M Blythb,f,g and Emily Banksg,h, on behalf of the High Risk Prescribing Investigators a Faculty of Pharmacy, University of Sydney, NSW, Australia b Sydney Medical School, University of Sydney, NSW, Australia c Sydney School of Public Health, University of Sydney, NSW, Australia d Royal North Shore Hospital and Kolling Institute of Medical Research, Sydney, NSW, Australia e School of Computing, Engineering and Mathematics, University of Western Sydney, NSW, Australia f Centre for Education and Research on Ageing (CERA), Concord Hospital, Sydney, NSW, Australia g The Sax Institute, Sydney, NSW, Australia h National Centre for Epidemiology and Population Health, Australian National University, Canberra, ACT i Corresponding author: [email protected] Article history Abstract Publication date: March 2015 Background: Increasingly, automated methods are being used to code free- Citation: Gnjidic D, Pearson S, Hilmer S, text medication data, but evidence on the validity of these methods is limited. Basilakis J, Schaffer AL, Blyth FM, Banks E. To examine the accuracy of automated coding of previously keyed Manual versus automated coding of free-text Aim: in free-text medication data compared with manual coding of original self-reported medication data in the 45 and Up Study: a validation study. Public Health handwritten free-text responses (the ‘gold standard’).
    [Show full text]
  • Acid-Reducing Medications: Interactions with Harvoni and Epclusa
    November 2016 | www.hepatitis.va.gov Acid-Reducing Medications: Interactions with Harvoni® and Epclusa® Sofosbuvir/Velpatasvir = Epclusa® Ledipasvir/Sofosbuvir = Harvoni® • Acid-reducing medications can decrease the effectiveness of Harvoni® and Epclusa® and could prevent successful cure. • Let your provider know if you are taking any acid-reducing medications—either prescribed to you or purchased over the counter. Types of Acid-Reducing What to Do if What to Do if Medications Taking Epclusa® Taking Harvoni® Antacids Separate taking the antacid and Separate taking the antacid and Epclusa® by 4 hours Harvoni® by 4 hours Combinations of aluminum, magnesium, and calcium. Brand names include: Alka-Seltzer® Maalox® Mylanta® Rolaids® TUMS® H2 Blockers Do not take more than the Do not take more than the recommended doses recommended doses Cimetidine (Tagamet®) Famotidine (Pepcid®) May take together with Epclusa® May take together with Harvoni® Nizatidine (Axid®) or 12 hours apart or 12 hours apart Ranitidine (Zantac®) Proton Pump Inhibitors (PPI) It is best to avoid PPIs during treat- It is best to avoid PPIs during ment with Epclusa®. If there are no treatment with Harvoni®. If there Esomeprazole (Nexium®) alternatives, follow these instructions: are no alternatives, follow these Lansoprazole (Prevacid®) instructions: Omeprazole (Prilosec®) Take Epclusa® with food Pantoprazole (Protonix®) Take the proton pump inhibitor 4 Take Harvoni® and the proton Rabeprazole (Aciphex®) hours after taking Epclusa® pump inhibitor at the same time in the morning after fasting overnight Do not take the proton pump (on an empty stomach) inhibitor at the same time as Epclusa® Do not take proton pump Do not take proton pump inhibitors inhibitors at more than the at more than the recommended dose recommended dose U.S.
    [Show full text]
  • Medication Guide Esomeprazole Magnesium
    MEDICATION GUIDE ESOMEPRAZOLE MAGNESIUM DELAYED-RELEASE CAPSULES, USP (es″ oh mep′ ra zole mag nee′ zee um) 20 mg and 40 mg Read the Medication Guide that comes with esomeprazole magnesium delayed-release capsules before you start taking esomeprazole magnesium delayed-release capsules and each time you get a refill. There may be new information. This information does not take the place of talking with your doctor about your medical condition or your treatment. What is the most important information I should know about esomeprazole magnesium delayed-release capsules? Esomeprazole magnesium delayed-release capsules may help your acid-related symptoms, but you could still have serious stomach problems. Talk with your doctor. Esomeprazole magnesium delayed-release capsules can cause serious side effects, including: • Diarrhea. Esomeprazole magnesium delayed-release capsules may increase your risk of getting severe diarrhea. This diarrhea may be caused by an infection ( Clostridium difficile) in your intestines. • Call your doctor right away if you have watery stool, stomach pain, and fever that does not go away. • Bone fractures. People who take multiple daily doses of Proton Pump Inhibitor medicines for a long period of time (a year or longer) may have an increased risk of fractures of the hip, wrist, or spine. You should take esomeprazole magnesium delayed-release capsules exactly as prescribed, at the lowest dose possible for your treatment and for the shortest time needed. Talk to your doctor about your risk of bone fracture if you take esomeprazole magnesium delayed-release capsules. • Esomeprazole magnesium delayed-release capsules can have other serious side effects. See “What are the possible side effects of esomeprazole magnesium delayed-release capsules?” What are esomeprazole magnesium delayed-release capsules? Esomeprazole magnesium delayed-release capsules are a prescription medicine called a proton pump inhibitor (PPI).
    [Show full text]
  • Astrazeneca Plc
    6/15/2020 AstraZeneca - Wikipedia AstraZeneca AstraZeneca plc[3] is a British-Swedish multinational pharmaceutical and biopharmaceutical company with its global AstraZeneca plc headquarters in Cambridge, England.[4] Its R&D is concentrated in Cambridge, Gaithersburg, Maryland, and Mölndal in Sweden.[5] AstraZeneca has a portfolio of products for major disease areas including cancer, cardiovascular, gastrointestinal, infection, Type Public limited neuroscience, respiratory and inflammation.[6] company Traded as LSE: AZN (https:// The company was founded in 1999 through the merger of the www.londonstocke [7][8] Swedish Astra AB and the British Zeneca Group (itself formed xchange.com/exch by the demerger of the pharmaceutical operations of Imperial ange/searchengin Chemical Industries in 1993). Since the merger it has been among e/search.html?lang the world's largest pharmaceutical companies and has made =en&x=0&y=0&q= numerous corporate acquisitions, including Cambridge Antibody AZN) Technology (in 2006), MedImmune (in 2007), Spirogen (in 2013) NYSE: AZN (http and Definiens (by MedImmune in 2014). s://www.nyse.com/ quote/XNYS:AZN) AstraZeneca has a primary listing on the London Stock Exchange Nasdaq and is a constituent of the FTSE 100 Index. It has secondary listings Stockholm: AZN (ht on the New York Stock Exchange and the OMX exchange. tp://www.nasdaqom xnordic.com/aktier/ microsite?language Contents Id=1&Instrument=S SE3524) History FTSE 100 2000–06 Component 2007–12: The patent cliff and subsequent acquisitions ISIN GB0009895292 2013
    [Show full text]
  • Proton Pump Inhibitors
    Cigna National Formulary Coverage Policy Step Therapy Proton Pump Inhibitors Table of Contents Product Identifier(s) National Formulary Medical Necessity ................ 1 14530 Conditions Not Covered....................................... 2 Background .......................................................... 2 References .......................................................... 3 Revision History ................................................... 4 INSTRUCTIONS FOR USE The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer’s benefit plan document may contain a specific exclusion related to a topic addressed in a Coverage Policy. In the event of a conflict, a customer’s benefit plan document always supersedes the information in the Coverage Policies. In the absence of a controlling federal or state coverage mandate, benefits are ultimately determined by the terms of the applicable benefit plan document. Coverage determinations in each specific instance require consideration of 1) the terms of the applicable benefit plan document in effect on the date of service; 2) any applicable laws/regulations; 3) any relevant collateral source materials including Coverage Policies and; 4) the specific facts of the particular situation.
    [Show full text]
  • New and Future Drug Development for Gastroesophageal Reflux Disease
    J Neurogastroenterol Motil, Vol. 20 No. 1 January, 2014 pISSN: 2093-0879 eISSN: 2093-0887 http://dx.doi.org/10.5056/jnm.2014.20.1.6 JNM Journal of Neurogastroenterology and Motility Review New and Future Drug Development for Gastroesophageal Reflux Disease Carla Maradey-Romero and Ronnie Fass* The Esophageal and Swallowing Center, Division of Gastroenterology and Hepatology, MetroHealth Medical Center, Case Western Reserve University, Cleveland, Ohio, USA Medical therapy remains the most popular treatment for gastroesophageal reflux disease (GERD). Whilst interest in drug devel- opment for GERD has declined over the last few years primarily due to the conversion of most proton pump inhibitor (PPI)’s to generic and over the counter compounds, there are still numerous areas of unmet needs in GERD. Drug development has been focused on potent histamine type 2 receptor antagonist’s, extended release PPI’s, PPI combination, potassium-competitive acid blockers, transient lower esophageal sphincter relaxation reducers, prokinetics, mucosal protectants and esophageal pain modulators. It is likely that the aforementioned compounds will be niched for specific areas of unmet need in GERD, rather than compete with the presently available anti-reflux therapies. (J Neurogastroenterol Motil 2014;20:6-16) Key Words Erosive esophagitis; Gastroesophageal reflux; Heartburn; Proton pump inhibitors Most patients with GERD fall into 1 of 3 categories: non- erosive reflux disease (NERD), erosive esophagitis (EE), and Introduction Barrett’s esophagus (BE). The 2 main phenotypes of GERD, Gastroesophageal reflux disease (GERD) is a common con- NERD and EE, appear to have different pathophysiological and dition that develops when reflux of stomach contents cause trou- clinical characteristics.
    [Show full text]
  • Nda 20-839/S-044 Supplement Approval
    DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration Silver Spring MD 20993 NDA 20-839/S-044 SUPPLEMENT APPROVAL Sanofi-Aventis U.S. Inc. Attention: Colleen M. Davenport, Ph.D. Director, Drug Regulatory Affairs 11 Great Valley Parkway P.O. Box 3026 Malvern, PA 19355 Dear Dr. Davenport: Please refer to your supplemental new drug application dated November 2, 2009, received November 2, 2009, submitted under section 505(b) of the Federal Food, Drug, and Cosmetic Act (FDCA) for Plavix (clopidogrel bisulfate) 75 mg Tablets. This Changes Being Effected supplemental new drug application provides information regarding a potential drug interaction between clopidogrel and CYP2C19 inhibitors. The new label revisions are as follows: 1. The following text was added to the beginning of the WARNINGS section: Reduced effectiveness due to impaired CYP2C19 function: The inhibition of platelet aggregation by clopidogrel is entirely due to an active metabolite. Clopidogrel is metabolized to this active metabolite in part by CYP2C19. This metabolism can be impaired by genetic variations in CYP2C19 and by concomitant medications that interfere with CYP2C19. Avoid use of Plavix in patients with impaired CYP2C19 function due to known genetic variation or due to drugs that inhibit CYP2C19 activity. Genetic variations: Patients with genetically reduced CYP2C19 function have diminished antiplatelet responses and generally exhibit higher cardiovascular event rates following myocardial infarction than do patients with normal CYP2C19 function (see CLINICAL PHARMACOLOGY: Pharmacogenetics). Drug interactions: Co-administration of Plavix with omeprazole, a proton pump inhibitor that is an inhibitor of CYP2C19, reduces the pharmacological activity of Plavix if given concomitantly or if given 12 hours apart.
    [Show full text]
  • Estonian Statistics on Medicines 2013 1/44
    Estonian Statistics on Medicines 2013 DDD/1000/ ATC code ATC group / INN (rout of admin.) Quantity sold Unit DDD Unit day A ALIMENTARY TRACT AND METABOLISM 146,8152 A01 STOMATOLOGICAL PREPARATIONS 0,0760 A01A STOMATOLOGICAL PREPARATIONS 0,0760 A01AB Antiinfectives and antiseptics for local oral treatment 0,0760 A01AB09 Miconazole(O) 7139,2 g 0,2 g 0,0760 A01AB12 Hexetidine(O) 1541120 ml A01AB81 Neomycin+Benzocaine(C) 23900 pieces A01AC Corticosteroids for local oral treatment A01AC81 Dexamethasone+Thymol(dental) 2639 ml A01AD Other agents for local oral treatment A01AD80 Lidocaine+Cetylpyridinium chloride(gingival) 179340 g A01AD81 Lidocaine+Cetrimide(O) 23565 g A01AD82 Choline salicylate(O) 824240 pieces A01AD83 Lidocaine+Chamomille extract(O) 317140 g A01AD86 Lidocaine+Eugenol(gingival) 1128 g A02 DRUGS FOR ACID RELATED DISORDERS 35,6598 A02A ANTACIDS 0,9596 Combinations and complexes of aluminium, calcium and A02AD 0,9596 magnesium compounds A02AD81 Aluminium hydroxide+Magnesium hydroxide(O) 591680 pieces 10 pieces 0,1261 A02AD81 Aluminium hydroxide+Magnesium hydroxide(O) 1998558 ml 50 ml 0,0852 A02AD82 Aluminium aminoacetate+Magnesium oxide(O) 463540 pieces 10 pieces 0,0988 A02AD83 Calcium carbonate+Magnesium carbonate(O) 3049560 pieces 10 pieces 0,6497 A02AF Antacids with antiflatulents Aluminium hydroxide+Magnesium A02AF80 1000790 ml hydroxide+Simeticone(O) DRUGS FOR PEPTIC ULCER AND GASTRO- A02B 34,7001 OESOPHAGEAL REFLUX DISEASE (GORD) A02BA H2-receptor antagonists 3,5364 A02BA02 Ranitidine(O) 494352,3 g 0,3 g 3,5106 A02BA02 Ranitidine(P)
    [Show full text]