DOCSLIB.ORG

Report on the Deliberation Results December 1, 2010 Evaluation And

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Report on the Deliberation Results December 1, 2010 Evaluation And Report on the Deliberation Results December 1, 2010 Evaluation and Licensing Division, Pharmaceutical and Food Safety Bureau Ministry of Health, Labour and Welfare [Brand name] Pradaxa Capsules 75 mg Pradaxa Capsules 110 mg (The proposed Japanese brand name will be changed.) [Non-proprietary name] Dabigatran Etexilate Methanesulfonate (JAN*) [Applicant] Nippon Boehringer Ingelheim Co., Ltd. [Date of application] March 4, 2010 [Results of deliberation] In the meeting held on November 24, 2010, the First Committee on New Drugs concluded that the product may be approved and that this result should be presented to the Pharmaceutical Affairs Department of the Pharmaceutical Affairs and Food Sanitation Council. The product is not classified as a biological product or a specified biological product, the re-examination period is 8 years, and neither the drug substance nor the drug product is classified as a poisonous drug or a powerful drug. *Japanese Accepted Name (modified INN) This English version of the Japanese review report is intended to be a reference material to provide convenience for users. In the event of inconsistency between the Japanese original and this English translation, the former shall prevail. The PMDA will not be responsible for any consequence resulting from the use of this English version Review Report November 16, 2010 Pharmaceuticals and Medical Devices Agency, Japan The results of a regulatory review by the Pharmaceuticals and Medical Devices Agency on the following pharmaceutical product submitted for registration are as follows. [Brand name] Pradaxa Capsules 75 mg Pradaxa Capsules 110 mg (The proposed Japanese brand name will be changed.) [Non-proprietary name] Dabigatran Etexilate Methanesulfonate [Name of applicant] Nippon Boehringer Ingelheim Co., Ltd. [Date of application] March 4, 2010 [Dosage form/Strength] Hard capsules: Each capsule contains 75 mg or 110 mg of Dabigatran Etexilate Methanesulfonate [Application classification] Prescription drug (1) Drug with a new active ingredient [Chemical structure] CH3 CH3 O N O N O N N H NH O N 2 O N CH 3 . CH3SO3H Molecular formula: C34H41N7O5·CH4O3S Molecular weight: 723.86 Chemical name: Ethyl 3-({[2-({[4-(amino{[(hexyloxy)carbonyl]imino}methyl)phenyl]amino} methyl)-1-methyl-1H-benzoimidazol-5-yl]carbonyl}(pyridin-2-yl)amino)prop anoate monomethanesulfonate [Items warranting special mention] None [Reviewing office] Office of New Drug II This English version of the Japanese review report is intended to be a reference material to provide convenience for users. In the event of inconsistency between the Japanese original and this English translation, the former shall prevail. The PMDA will not be responsible for any consequence resulting from the use of this English version Review Results November 16, 2010 [Brand name] Pradaxa Capsules 75 mg Pradaxa Capsules 110 mg (The proposed Japanese brand name will be changed.) [Non-proprietary name] Dabigatran Etexilate Methanesulfonate [Name of applicant] Nippon Boehringer Ingelheim Co., Ltd. [Date of application] March 4, 2010 [Results of review] Based on the submitted data, it is concluded that the efficacy of Pradaxa Capsules 75 mg and Pradaxa Capsules 110 mg in reducing the risk of ischaemic stroke and systemic embolism in patients with non- valvular atrial fibrillation has been demonstrated and their safety is acceptable in view of their observed benefits. Through the post-marketing surveillance, it is considered important to collect the safety information including bleeding risk in patients who receive concomitant antiplatelet therapy, elderly patients, and patients with renal impairment; safety information regarding gastrointestinal disorder or gastrointestinal haemorrhage; and safety information on concomitant drugs that are considered to affect the plasma concentration of dabigatran etexilate, the safety at each dose, and onset of myocardial infarction. As a result of its regulatory review, the Pharmaceuticals and Medical Device Agency has concluded that Pradaxa Capsules 75 mg and Pradaxa Capsules 110 mg may be approved for the following indication, and dosage and administration. [Indication] Reduction in the risk of ischaemic stroke and systemic embolism in patients with non-valvular atrial fibrillation [Dosage and administration] The usual adult dosage is 150 mg (two 75 mg capsules) of dabigatran etexilate administered orally twice daily. The dose should be reduced to 110 mg of dabigatran etexilate (one 110 mg capsule) twice daily, as needed. 3 Review Report (1) October 25, 2010 I. Product Submitted for Registration [Brand name] Pradaxa Capsules 75 mg Pradaxa Capsules 110 mg (The proposed Japanese brand name will be changed.) [Non-proprietary name] Dabigatran Etexilate Methanesulfonate [Name of applicant] Nippon Boehringer Ingelheim Co., Ltd. [Date of application] March 4, 2010 [Dosage form/Strength] Hard capsules: Each capsule contains 75 mg or 110 mg of Dabigatran Etexilate Methanesulfonate [Proposed indication] Reduction in the risk of stroke and systemic embolism in patients with atrial fibrillation [Proposed dosage and administration] The usual adult dosage is 150 mg (two 75 mg capsules) of Dabigatran Etexilate administered orally twice daily. [Items warranting special mention] None II. Summary of the Submitted Data and Outline of the Review by the Pharmaceuticals and Medical Devices Agency A summary of the data submitted in the application and an outline of the review by the Pharmaceuticals and Medical Devices Agency (PMDA) are as shown below. 1. Origin or history of discovery and usage conditions in foreign countries etc. Dabigatran Etexilate (dabigatran etexilate) Methanesulfonate is an oral pro-drug of a non-peptide, direct thrombin inhibitor developed by Boehringer Ingelheim International GmbH, Germany. Dabigatran etexilate methanesulfonate does not exhibit antithrombin activity, but is converted by esterase to dabigatran that is the active substance when absorbed from the gastrointestinal tract. Dabigatran inhibits thrombogenicity by selectively and reversibly inhibiting thrombin, an important enzyme in the blood coagulation cascade. Large-scale, multiregional clinical studies were conducted in foreign countries, and a marketing application for dabigatran was submitted in December 2009 in both the United States and Europe for the indication of reducing the risk of stroke and systemic embolism in patients with atrial fibrillation. On October 19, 2010, dabigatran gained its first approval in the US for the indication of “reducing the risk of stroke in patients with non-valvular atrial fibrillation.” On the other hand, dabigatran was approved for the indication of “primary prevention of venous thromboembolic events in adult patients who have undergone total hip 4 replacement surgery or total knee replacement surgery” in Europe in March 2008, and since then, it has been approved for the same indication in 74 countries as of May 2010. In Japan, the drug development was started by Nippon Boehringer Ingelheim Co., Ltd. in 20**. A marketing application has been submitted based on the data from clinical studies in Japan and the above mentioned multiregional clinical studies involving Japanese. 2. Data relating to quality 2.A Summary of the submitted data Pradaxa capsules 75 mg and Pradaxa capsules 110 mg (hereinafter collectively called “the proposed product”) are hard capsules containing 86.48 and 126.83 mg, respectively, of dabigatran etexilate methanesulfonate (with a molecular formula of C34H41N7O5·CH4O3S, and a molecular weight of 723.86) (they are equivalent to 75 and 110 mg of dabigatran etexilate, respectively). 2.A.(1) Drug substance 2.A.(1).1) Characterization (a) Structure The chemical structure of the drug substance has been confirmed by elementary analysis, mass spectrometry, ultraviolet and visible absorption spectrum, infrared spectrophotometry (IR), hydrogen nuclear magnetic resonance spectrometry (1H-NMR), and carbon nuclear magnetic resonance spectrometry. (b) General properties The general properties of the drug substance, including description, melting point, dissociation constant (pKa), partition coefficient, hygroscopicity, solubility, and crystalline polymorphism, have been determined. It is a yellow-white to yellow crystalline powder with a melting point around 180C. ******** ************************************************************************************** ************************************************************************************** ************************************************************************************** *************************************************************************** It was freely soluble in methanol, soluble in N,N-Dimethylacetamide, sparingly soluble in ethanol (99.9) and practically insoluble in water. Polymorphism was observed and two different crystalline forms (crystalline form I and II) were identified. 2.A.(1).2) Manufacturing process The drug substance is manufactured by the manufacturing process A or B. Manufacturing process A Step 1:******************************************************************************** ************************************************************************************** ************************************************************************************** ************************************************************************************** 5 ************************************************************************************** **************************************************************************************
Load more

Recommended publications
  • Dabigatran, Rivaroxaban, and Warfarin in the Oldest Adults With
    CLINICAL INVESTIGATION Dabigatran, Rivaroxaban, and Warfarin in the Oldest Adults with Atrial Fibrillation in Taiwan Chao-Lun Lai, MD, PhD,*†‡§ Ho-Min Chen, MS,† Min-Tsun Liao, MD,* and Ting-Tse Lin, MD* mortality and cardiovascular mortality than those who OBJECTIVES: To compare the effectiveness and safety of used warfarin. Reduced-dose dabigatran was also associ- reduced-dose dabigatran, reduced-dose rivaroxaban, and warfa- ated with lower risk of intracranial hemorrhage than war- rin in individuals aged 85 and older with atrial fibrillation (AF). farin. J Am AmGeriatr GeriatrSoc Soc66:1567–1574, 2018. 2018. DESIGN: Retrospective cohort study. SETTING: Taiwan National Health Insurance claims database, 20112015. Key words: dabigatran; rivaroxaban; warfarin; effec- PARTICIPANTS: Individuals with AF aged 85 and older tiveness; safety; octogenarian (mean 88.6) with incident use of oral anticoagulants between June 1, 2012 and May 31, 2015 (N54,722; dabi- gatran 110 mg, n51,489; rivaroxaban 15 mg/10 mg, n51,736; warfarin, n51,497). MEASUREMENTS: Clinical outcomes included all-cause death, cardiovascular death, ischemic stroke, acute myocardial he risk of ischemic stroke is 5 times as high in individ- infarction, arterial embolism or thrombosis, intracranial hem- T uals with atrial fibrillation (AF) than in those with- orrhage, and gastrointestinal hemorrhage needing transfusion. out.1 Warfarin, the classic vitamin K antagonist, can reduce 2 Propensity score–matched analysis was performed, and the the risk of ischemic stroke by approximately 60%, but the marginal proportional hazards model was used to estimate the narrow therapeutic window and risk of bleeding complica- relative risk of various clinical outcomes in a matched tions associated with warfarin therapy have led to its being 1 dabigatran-warfarin cohort (n51,180 in each group) and a underused.
    [Show full text]
  • DOACS COMPARISON and Faqs
    NOACS/DOACS*: PRACTICAL ISSUES AND FREQUENTLY-ASKED QUESTIONS OBJECTIVES: • To summarize characteristics of the direct oral anticoagulants (DOACs) currently available in Canada. • To address common practical issues related to DOAC use. • To address frequently asked questions regarding DOACs. BACKGROUND: The DOACs, which consist of apixaban, dabigatran, edoxaban, and rivaroxaban are used for the prevention and treatment of venous thromboembolism (VTE) and for stroke prevention in atrial fibrillation (AF). Practical advantages of DOACs over warfarin include fixed once- or twice-daily oral dosing without the need for coagulation test monitoring, relatively fewer known drug interactions and no known food interactions. Like warfarin, DOACs increase the risk for bleeding and should be administered under close clinical monitoring. Practical issues regarding the everyday use of DOACs will be addressed in this guide. PRACTICAL AND LIFESTYLE ISSUES: Can DOACs be taken with meals? Rivaroxaban should be taken with meals to enhance absorption; the tablet can be crushed and taken with soft foods such as applesauce. Apixaban, dabigatran, edoxaban can be taken with or without meals. However, taking dabigatran with meals can reduce dyspepsia. Dabigatran capsules should not be opened, broken or chewed before swallowing. Are there any foods or beverages that need to be avoided with DOACs? Unlike with warfarin, there are no known food interactions with DOACs, so there are no food restrictions when taking these medications. In addition, there is no evidence that drinking grapefruit juice affects the effectiveness or safety of DOACs. In general, it is acceptable for patients taking a DOAC to drink alcoholic beverages in moderation (e.g. a glass of wine with a meal) as it is for patients on warfarin.
    [Show full text]
  • Atrial Fibrillation
    CONFIDENTIAL NATIONAL INSTITUTE FOR HEALTH AND CLINICAL EXCELLENCE Premeeting briefing Dabigatran for the prevention of stroke and systemic embolism in atrial fibrillation This briefing presents the key issues arising from the manufacturer’s submission, Evidence Review Group (ERG) report and statements made by consultees and their nominated clinical specialists and patient experts. Please note that this briefing is a summary of the information available and should be read with the full supporting documents. The manufacturer was asked to…. provide justification for reducing the dabigatran treatment dose from 150 mg to 110 mg at 80 years of age comment on the impact of being unable to utilise P-glycoprotein inhibitors on the use of dabigatran and the management of atrial fibrillation provide a justification for choosing the mixed treatment comparison (MTC) (SAS) for the base case instead of the results from the MTC (WinBUGs) provide a comparison of the different hazard ratios from the MTC (SAS), MTC (WinBUGS) analyses and the direct pairwise results and justify any discrepancies justify the exclusion of trials with zero event arms from the MTC provide a revised model with the ability to choose any of the included treatments (dabigatran or warfarin) as either a first-line or a second-line treatment option provide base-case cost-effectiveness results comparing dabigatran 110 mg and 150 mg when used as either first-line treatment or as a second-line treatment following warfarin analyse and provide base-case cost-effectiveness comparing the results of the following treatment sequences: dabigatran → warfarin → aspirin → no treatment and warfarin → aspirin → no treatment.
    [Show full text]
  • Laboratory Monitoring of Direct Oral Anticoagulants (Doacs)
    biomedicines Review Laboratory Monitoring of Direct Oral Anticoagulants (DOACs) Claire Dunois HYPHEN BioMed, Sysmex Group, 95000 Neuville sur Oise, France; [email protected] Abstract: The introduction of direct oral anticoagulants (DOACs), such as dabigatran, rivaroxaban, apixaban, edoxaban, and betrixaban, provides safe and effective alternative to previous anticoagulant therapies. DOACs directly, selectively, and reversibly inhibit factors IIa or Xa. The coagulation effect follows the plasma concentration–time profile of the respective anticoagulant. The short half-life of a DOAC constrains the daily oral intake. Because DOACs have predictable pharmacokinetic and pharmacodynamic responses at a fixed dose, they do not require monitoring. However in specific clinical situations and for particular patient populations, testing may be helpful for patient management. The effect of DOACs on the screening coagulation assays such as prothrombin time (PT), activated partial thromboplastin time (APTT), and thrombin time (TT) is directly linked to reagent composition, and clotting time can be different from reagent to reagent, depending on the DOAC’s reagent sensitivity. Liquid chromatography–mass spectrometry (LC-MS/MS) is considered the gold standard method for DOAC measurement, but it is time consuming and requires expensive equipment. The general consensus for the assessment of a DOAC is clotting or chromogenic assays using specific standard calibrators and controls. This review provides a short summary of DOAC properties and an update on laboratory methods for measuring DOACs. Keywords: DOAC; monitoring; screening assays; quantitative assays Citation: Dunois, C. Laboratory Monitoring of Direct Oral Anticoagulants (DOACs). 1. Introduction Biomedicines 2021, 9, 445. https:// Direct oral anticoagulants (DOACs) constitute first-line therapy used for many throm- doi.org/10.3390/biomedicines9050445 boembolic indications, such as prevention and treatment of venous thromboembolism (VTE) and stroke prevention in atrial fibrillation (AF) [1,2].
    [Show full text]
  • Anticoagulant Pradaxa (Dabigatran Etexilate Mesylate) Savaysa (Edoxaban) Xarelto 2.5Mg (Rivaroxaban) Effective 01/01/2021
    Anticoagulant Pradaxa (dabigatran etexilate mesylate) Savaysa (edoxaban) Xarelto 2.5mg (rivaroxaban) Effective 01/01/2021 ☒ MassHealth Plan ☒ ☐Commercial/Exchange Prior Authorization Program Type ☒ Quantity Limit ☒ Pharmacy Benefit Benefit ☐ Step Therapy ☐ Medical Benefit (NLX) Specialty N/A Limitations Specialty Medications All Plans Phone: 866-814-5506 Fax: 866-249-6155 Non-Specialty Medications Contact MassHealth Phone: 877-433-7643 Fax: 866-255-7569 Information Commercial Phone: 800-294-5979 Fax: 888-836-0730 Exchange Phone: 855-582-2022 Fax: 855-245-2134 Medical Specialty Medications (NLX) All Plans Phone: 844-345-2803 Fax: 844-851-0882 Exceptions N/A Overview Xarelto and Savaysa are factor Xa inhibitors which inhibit platelet activation and fibrin clot formation. Pradaxa is a thrombin inhibitor which blocks free and fibrin bound thrombin. These medications are indicated for: . Treatment of deep venous thrombosis (DVT) and pulmonary embolism (PE) – Pradaxa and Savaysa . Prevention of stroke and systemic embolism in patients with nonvalvular atrial fibrillation. – Pradaxa, Xarelto, and Savaysa . Prophylaxis of DVT and/or PE in patients who have undergone total hip arthroplasty. - Xarelto and Pradaxa . Prophylaxis of venous thromboembolism (VTE) – Xarelto . Reduction in the risk of recurrence of deep vein thrombosis (DVT) and pulmonary embolism (PE) – Xarelto . Reduction of risk of major cardiovascular (CV) events (CV death, myocardial infarction, and stroke) in patients with coronary artery disease (chronic) or peripheral artery disease. - Xarelto No PA PA required Pradaxa® (dabigatran etexilate mesylate 110 mg) ≤ 70 Pradaxa® (dabigatran etexilate mesylate 75 mg, 150 capsules/365 days mg) Pradaxa® (dabigatran etexilate mesylate 110 mg) > 70 Eliquis® (apixaban) PD capsules/365 days ® ® Xarelto (rivaroxaban 10 mg, 15 mg, 20 mg, starter pack) Savaysa (edoxaban) ® Xarelto (rivaroxaban 2.5 mg tablet) PD Preferred Drug.
    [Show full text]
  • Estonian Statistics on Medicines 2016 1/41
    Estonian Statistics on Medicines 2016 ATC code ATC group / Active substance (rout of admin.) Quantity sold Unit DDD Unit DDD/1000/ day A ALIMENTARY TRACT AND METABOLISM 167,8985 A01 STOMATOLOGICAL PREPARATIONS 0,0738 A01A STOMATOLOGICAL PREPARATIONS 0,0738 A01AB Antiinfectives and antiseptics for local oral treatment 0,0738 A01AB09 Miconazole (O) 7088 g 0,2 g 0,0738 A01AB12 Hexetidine (O) 1951200 ml A01AB81 Neomycin+ Benzocaine (dental) 30200 pieces A01AB82 Demeclocycline+ Triamcinolone (dental) 680 g A01AC Corticosteroids for local oral treatment A01AC81 Dexamethasone+ Thymol (dental) 3094 ml A01AD Other agents for local oral treatment A01AD80 Lidocaine+ Cetylpyridinium chloride (gingival) 227150 g A01AD81 Lidocaine+ Cetrimide (O) 30900 g A01AD82 Choline salicylate (O) 864720 pieces A01AD83 Lidocaine+ Chamomille extract (O) 370080 g A01AD90 Lidocaine+ Paraformaldehyde (dental) 405 g A02 DRUGS FOR ACID RELATED DISORDERS 47,1312 A02A ANTACIDS 1,0133 Combinations and complexes of aluminium, calcium and A02AD 1,0133 magnesium compounds A02AD81 Aluminium hydroxide+ Magnesium hydroxide (O) 811120 pieces 10 pieces 0,1689 A02AD81 Aluminium hydroxide+ Magnesium hydroxide (O) 3101974 ml 50 ml 0,1292 A02AD83 Calcium carbonate+ Magnesium carbonate (O) 3434232 pieces 10 pieces 0,7152 DRUGS FOR PEPTIC ULCER AND GASTRO- A02B 46,1179 OESOPHAGEAL REFLUX DISEASE (GORD) A02BA H2-receptor antagonists 2,3855 A02BA02 Ranitidine (O) 340327,5 g 0,3 g 2,3624 A02BA02 Ranitidine (P) 3318,25 g 0,3 g 0,0230 A02BC Proton pump inhibitors 43,7324 A02BC01 Omeprazole
    [Show full text]
  • Center for Drug Evaluation and Research Application
    CENTER FOR DRUG EVALUATION AND RESEARCH APPLICATION NUMBER: 22-512 PHARMACOLOGY REVIEW(S) Tertiary Pharmacology Review By: Paul C. Brown, Ph.D., ODE Associate Director for Pharmacology and Toxicology OND IO NDA: 22-307 Submission date: 4/19/2010 Drug: Pradaxa™ (Dabigatran etexilate mesylate) Sponsor: Boehringer Ingelheim Pharma GmbH & Co. KG Indication: Prevention of stroke and systemic embolism in patients with atrial fibrillation Reviewing Division: Division of Cardiovascular and Renal Products Comments: The pharm/tox reviewer and supervisor found the nonclinical information submitted for dabigatran to be sufficient to support the proposed use. The reviewer proposes pregnancy category C for the labeling. Dabigatran induced some reproductive toxicity in rats manifest as a decreased number of implantations, decreased number of viable fetuses, increase in the resorption rate, increase in post-implantation loss, and an increase in the number of dead offspring when given at doses of 70 mg/kg (about 2.6 to 3 times the MRHD of 300 mg/day on a mg/m2 basis). Dabigatran also induced some fetal structural variations but did not induce fetal malformations in rats or rabbits. Dabigatran was evaluated for carcinogenicity in 2-year rat and mouse studies. The Executive Carcinogenicity Assessment Committee concluded that these studies were adequate and there were no drug-related tumors in either study. Conclusions: I concur with the Division pharm/tox conclusion that the nonclinical data support approval of this NDA. No additional nonclinical studies are recommended at this time. The proposed Established Pharmacologic Class for dabigatran is "direct thrombin inhibitor". This is appropriate because it is consistent with other moieties of this class.
    [Show full text]
  • Periprocedural Management of Patients on Dabigatran Etexilate
    Periprocedural Management of Patients on Dabigatran lation tests are not necessary to monitor the effect of dabigatran. Etexilate Treatment However, there is a need to quantitate the intensity of anticoagulation Dabigatran etexilate is a direct thrombin inhibitor that was initially activity of dabigatran in such settings. Other tests such as the throm- introduced for oral anticoagulation for the prevention or treatment of bin time, activated partial thromboplastin time (aPTT), and ecarin venous thrombosis.1 After the recently concluded phase III trial Ran- clotting time have been reported to correlate with dabigatran serum domized Evaluation of Long-Term Anticoagulation Therapy,2 dab- concentration.3 4 igatran has been approved by the US Food and Drug Administration The Interventional Management of Stroke (IMS) III trial pro- as a potential replacement for warfarin in patients with nonvalvular posed that administration of tissue plasminogen activator or endo- atrial fibrillation to reduce the risk of stroke and systemic embolism. vascular intervention could be considered in patients at 48 hours after Dabigatran was administered, in a blinded fashion, in capsules con- last intake of dabigatran, or within 48 hours of the last intake and with taining either 110 or 150 mg of the drug, to be taken twice daily. normal aPTT in the same way as heparin. Because no guidelines exist With the anticipated increase in dabigatran use, neurointerven- on how to monitor the therapeutic activity effect of dabigatran accu- tionalists will face the challenge of making treatment decisions in rately, emergent neurointerventional procedures in dabigatran- patients on dabigatran. Patients with therapeutic levels of dabigatran treated patients should be approached cautiously.
    [Show full text]
  • PRADAXA Safely and Effectively
    HIGHLIGHTS OF PRESCRIBING INFORMATION ----------------------DOSAGE AND ADMINISTRATION----------------------­ These highlights do not include all the information needed to use Non-valvular Atrial Fibrillation: PRADAXA safely and effectively. See full prescribing information for o For patients with CrCl >30 mL/min: 150 mg orally, twice daily (2.1) PRADAXA. o For patients with CrCl 15-30 mL/min: 75 mg orally, twice daily (2.1) Treatment of DVT and PE: PRADAXA® (dabigatran etexilate mesylate) capsules, for oral use o For patients with CrCl >30 mL/min: 150 mg orally, twice daily after Initial U.S. Approval: 2010 5-10 days of parenteral anticoagulation (2.1) Reduction in the Risk of Recurrence of DVT and PE: WARNING: (A) PREMATURE DISCONTINUATION OF PRADAXA o For patients with CrCl >30 mL/min: 150 mg orally, twice daily after INCREASES THE RISK OF THROMBOTIC EVENTS, and previous treatment (2.1) (B) SPINAL/EPIDURAL HEMATOMA Prophylaxis of DVT and PE Following Hip Replacement Surgery: See full prescribing information for complete boxed warning o For patients with CrCl >30 mL/min: 110 mg orally first day, then 220 mg once daily (2.1) (A) PREMATURE DISCONTINUATION OF PRADAXA INCREASES Review recommendations for converting to or from other oral or parenteral THE RISK OF THROMBOTIC EVENTS: Premature discontinuation of anticoagulants (2.4, 2.5) any oral anticoagulant, including PRADAXA, increases the risk of Temporarily discontinue PRADAXA before invasive or surgical thrombotic events. To reduce this risk, consider coverage with another procedures when possible, then restart promptly (2.6) anticoagulant if PRADAXA is discontinued for a reason other than pathological bleeding or completion of a course of therapy (2.4, 2.5, 2.6, ---------------------DOSAGE FORMS AND STRENGTHS---------------------­ 5.1).
    [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]
  • PDF Download
    Review Article 201 How Do I Reverse Oral and Parenteral Anticoagulants? Wie Reversiere ich die Wirkung von Oralen und Parenteralen Antikoagulanzien? Jürgen Koscielny1 Edita Rutkauskaite1 Christoph Sucker2 Christian von Heymann3 1 Charité, Universitätsmedizin Berlin, Gerinnungsambulanz mit Address for correspondence Jürgen Koscielny, Charité, Hämophiliezentrum im Ambulanten, Gesundheitszentrum (AGZ), Universitätsmedizin Berlin, Gerinnungsambulanz mit Berlin, Germany HämophiliezentrumimAmbulantenGesundheitszentrum(AGZ), 2 Gerinnungszentrum Berlin Dr. Sucker, Berlin, Germany Berlin, Germany (e-mail: [email protected]). 3 Klinik für Anästhesie, Intensivmedizin, Notfallmedizin und Schmerztherapie, Vivantes Klinikum, Im Friedrichshain, Berlin, Germany Hämostaseologie 2020;40:201–213. Abstract An understanding of reversal strategies alone is important to safely and effectively care for patients in cases of bleeding or invasive procedures. The recent diversification in the number of licensed anticoagulants makes an understanding of drug-specific reversal strategies essential. Intravenous or oral vitamin K can reverse the effect of vitamin K antagonists (VKAs) within 12 to 48 hours and is indicated for any bleeding or an international normalized ratio >10 or 4.5 to 10 in patients with additional risk factors for bleeding. Furthermore, an additional administration of prothrombin complex concentrate (PCC) may be necessary in cases of major bleeding related to VKA. Protamine (chloride or sulfate) fully reverses the effect of unfractionated heparin and partially in low-molecular-weight heparin. Idarucizumab has been approved for dabigatran reversal, whereas andexanet alfa is approved for the reversal of some oral factor Xa inhibitors (apixaban, rivaroxaban). PCC seems to enhance the haemo- static potential for the reversal of the effect of FXa-inhibitors. So far, there are promising but only limited data on the efficacy of this approach available.
    [Show full text]
  • Non-Interventional (Ni) Study Protocol
    Apixaban B0661069 NON-INTERVENTIONAL STUDY PROTOCOL Update 1, 08 January 2016 NON-INTERVENTIONAL (NI) STUDY PROTOCOL Post Author isation Safet y St udi es (PA SS) infor mation Title CARBOS – Comparative risk of major bleeding with new oral anticoagulants (NOACs) and Phenprocoumon in patients with atrial fibrillation: a retrospective claims database study in Germany Protocol number B0661069 Protocol version identifier Update 1.0 Date of last version of protocol 08 January 2016 EU Post Authorisation Study (PAS) ENCEPP/SDPP/11313 register number Active substance Apixaban (B01AF02) Phenprocoumon (B01AA04) Rivaroxaban (B01AX06; B01AF01) Dabigatran (B01AX06) Product reference EU/1/11/691/006 EU/1/11/691/007 EU/1/11/691/008 EU/1/11/691/009 EU/1/11/691/010 EU/1/11/691/011 Pfizer Confidential Page 1 of 112 Apixaban B0661069 NON-INTERVENTIONAL STUDY PROTOCOL Update 1, 08 January 2016 EU/1/11/691/012 EU/1/11/691/014 Procedure number Not Available Marketing Authorisation Holder (MAH) Pfizer Pharma GmbH Joint PASS No Research question and objectives The aim of this study is to investigate whether there are differences in the occurrence of major bleeding events in patients with NVAF and prescribed oral anticoagulation therapies in a real-world setting. It will be investigated whether the occurrence of major bleeding events in NVAF patients under anticoagulant therapy differs between patients treated with VKA (e.g. Phenprocoumon) and patients treated with Apixaban, Dabigatran or Rivaroxaban respectively. Country of study Germany Author Fabian Volz Pfizer
    [Show full text]