Case Report Voriconazole in the Management of Invasive Aspergillosis in Two Patients with Acute Myeloid Leukemia Undergoing Stem Cell Transplantation

Total Page:16

File Type:pdf, Size:1020Kb

Case Report Voriconazole in the Management of Invasive Aspergillosis in Two Patients with Acute Myeloid Leukemia Undergoing Stem Cell Transplantation Bone Marrow Transplantation (2002) 30, 967–970 2002 Nature Publishing Group All rights reserved 0268–3369/02 $25.00 www.nature.com/bmt Case report Voriconazole in the management of invasive aspergillosis in two patients with acute myeloid leukemia undergoing stem cell transplantation D Mattei1, N Mordini1, C Lo Nigro1, D Ghirardo2, MT Ferrua3, M Osenda3, A Gallamini1, A Bacigalupo4 and C Viscoli5 1Hematology Department, S Croce Hospital, Cuneo, Italy; 2Radiology Department, S Croce Hospital, Cuneo, Italy; 3Laboratory Department, S Croce Hospital, Cuneo, Italy; 4Hematology Department, S Martino Hospital, Genoa, Italy; and 5National Cancer Institute, Genoa, Italy Summary: have also suggested the possible efficacy of oral itracona- zole (ITR) and liposomal amphotericin B (L AmB) for this The management of invasive aspergillosis in patients indication.9–11 In any case, even with prophylaxis, the with hematological malignancies remains controversial. relapse rate remains very high (33%), with a mortality rate A major problem is how to manage patients who had among relapsed patients of 88%.12 Therefore, there is a invasive aspergillosis during remission induction and clear need for new strategies for patients undergoing SCT consolidation therapy and then undergo SCT. Indeed who have a history of IA. Voriconazole (VOR) is a new in these patients the mortality rate related to invasive triazole derivative with potent, broad spectrum activity aspergillosis recurrence remains unacceptably high. We against the fungi responsible for opportunistic infections in report two cases of patients who underwent remission immunocompromised patients.13 The clinical efficacy, induction for AML, developed invasive aspergillosis safety and tolerance of VOR have been recently confirmed during antifungal prophylaxis with itraconazole, failed in two large clinical trials in patients with IA.14,15 amphotericin B deoxycholate and liposomal ampho- tericin B treatment, were successfully treated with vor- iconazole and eventually underwent SCT with voricona- Patients and methods zole prophylaxis without reactivation of invasive Patient 1 aspergillosis. Bone Marrow Transplantation (2002) 30, 967–970. In July 2000, a 44-year-old male with M4 AML received doi:10.1038/sj.bmt.1703763 induction therapy with hydroxyurea, daunorubicin (DNR), Keywords: acute myeloid leukemia; invasive aspergillo- etoposide (VP16) and cytarabine (Ara-C). Throughout ther- sis; voriconazole; stem cell transplantation apy, he received antifungal prophylaxis with ITR oral sol- ution (300 mg once daily) and was monitored with twice weekly serum ELISA tests for galactomannan (GAL) (BioRad Laboratories, Marnes La Coquette, France) and Invasive aspergillosis (IA) is an important cause of mor- weekly chest computer tomographic (CT) scans for the bidity in patients with AML, being reported in a proportion early detection of IA. On 10 July 2000, since the GAL 1,2 of patients ranging from 5 to 29%. Despite the avail- test had been positive in two consecutive samples, ITR was ability of new diagnostic procedures potentially able to replaced with D AmB (1 mg/kg/day for 21 days, followed 3,4 allow early treatment, the mortality rate remains unac- by L AmB 5 mg/kg/day for renal intolerance). Pulmonary 2,5–6 ceptably high (50–70%). Patients who survive the acute CT scans were sequentially performed: the first was nega- phase are usually successfully managed, due to antifungal tive despite the positive GAL test, but the second revealed treatment and bone marrow recovery. However, the causa- a right apical subpleuric nodule, that subsequently tive agent may remain in the infected tissues and can increased in size and then cavitated. Fine needle lung 7 reactivate following further courses of chemotherapy. biopsy under CT guidance was performed and culture grew Although no large scale prospective study has ever been Aspergillus species, confirming the diagnosis. The patient performed, there is some evidence that intravenous ampho- did not achieve remission and remained on L AmB, with tericin B deoxycholate (D AmB) may be effective as sec- partial clinical response, until September 2000. At this time, 8 ondary prophylaxis in SCT recipients. Scattered reports during salvage anti-leukemic therapy with DNR, high dose Ara-C, and VP16, he had relapsing fever and a new lesion Correspondence: Dr D Mattei, Divisione di Ematologia, Ospedale S Croce, in the right pulmonary apex was detected (Figure 1). L Via Michele Coppino 26, 12100 Cuneo, Italy AmB was discontinued for clinical evidence of failure and Received 13 March 2002; accepted 10 August 2002 VOR was started, first intravenously (6 mg/kg twice daily Voriconazole in the management of invasive aspergillosis D Mattei et al 968 Patient 2 In September 2000, a 57-year-old male with M2 AML received remission induction therapy with the same regi- men as described above. He was given the same antifungal prophylaxis and entered the same program of sequential GAL and CT scan monitoring of IA. On 26 September 2000 he started empirical antifungal therapy (first D AmB at 1 mg/kg/day, and then L AmB at 5 mg/kg/day) for per- sistent fever not responding to broad-spectrum antibiotics. Despite this treatment, on 27 September he suddenly presented with severe chest pain and hemoptisis. A chest CT scan showed bilateral nodular lesions (that eventually underwent cavitation) and, on the same day, the GAL ELISA turned out to be positive. A fine needle lung biopsy was attempted but failed for technical reasons. The patient showed partial response to L AmB, with defervescence but Figure 1 Patient 1: Chest CT scan before voriconazole treatment. no improvement in, and even slight enlargement of the pul- monary lesions (Figure 3). For this reason, on 24 October on day 1, then 4 mg/kg twice daily thereafter) and then L AmB was replaced with VOR (i.v. and then orally) at orally (150 mg twice daily). In October 2000, while in par- standard dosage, with clear improvement of the pulmonary tial remission, he underwent related HLA-identical BMT lesions. Following complete leukemia remission after conditioning with TBI 333 cGy once daily on days 1 (November 2000), the patient underwent consolidation to 3 (total dose 999 cGy) and cyclophosphamide (CTX) 60 therapy with ARA-C, DNR and filgrastim, with successful mg/kg once daily i.v. on days 6 and 7 (total dose 120 harvest of PBSC. He was then autografted in January 2001 mg/kg). GVHD prophylaxis consisted of cyclosporin A and after conditioning with busulfan (4 mg/kg p.o. in divided methotrexate. The overall clinical course was uneventful doses daily for 4 days to a total dose 16 mg/kg) and CTX with regard to infectious complications. VOR was adminis- (60 mg/kg once daily i.v. on days 5 and 6 for a total dose tered for a total of 45 days and discontinued at the begin- of 120 mg/kg). Since the CT scan still revealed bilateral ning of November 2000. At this point, the pulmonary CT cavitating lesions, VOR was continued until 13 February, scan was negative for any new lesions, with only one first intravenously and then orally. Throughout prophylaxis, residual micronodule at the right apex (Figure 2). Unfortu- the patient did not experience any major infectious compli- nately, in February 2001 the patient experienced AML cation, the GAL ELISA assays remained negative and the relapse. After additional chemotherapy (two courses of chest CT scan did not reveal any new lesions (Figure 4). fludarabine, Ara-C and mitoxantrone), in April 2001 he The patient is alive and free of both leukemia and IA 1 underwent a second related HLA-identical PBSCT without year after PBSCT. conditioning. New pulmonary lesions were detected on CT scanning, with borderline positive GAL antigenemia. For this reason, on 25 April VOR was restarted and continued Discussion until 28 June 2001. The patient died of refractory leukemia on 20 July 2001, without laboratory, clinical or radiological Patients with a history of IA appear to be at high risk of evidence of relapsed IA. reactivation when undergoing further chemotherapy. This is probably due to the fact that fungal organisms remain Figure 2 Patient 1: Chest CT scan after voriconazole treatment. Figure 3 Patient 2: Chest CT scan before voriconazole treatment. Bone Marrow Transplantation Voriconazole in the management of invasive aspergillosis D Mattei et al 969 Indeed, in both cases VOR was well tolerated, with no vis- ual hallucinations and only mild and transient WHO grade II hepatotoxicity in patient 1. This report confirms that IA occurring during the management of AML is not a contra- indication to intensive chemotherapy and allogeneic or autologous SCT. If strict diagnostic monitoring is applied and antifungal treatment is promptly initiated, patients can survive the acute phase. Then, if an effective and well-toler- ated antifungal treatment is administered pre-emptively for a prolonged period of time, relapse can be successfully pre- vented. Acknowledgements Voriconazole was supplied as compassionate treatment by Pfizer Central Research, Sandwich, UK. Figure 4 Patient 2: Chest CT scan after voriconazole treatment. viable in these lesions.16 Whether or not the risk of relapse References depends on the persistence of lesions is a matter of contro- versy. According to Martino et al,16 the risk is lower in 1 Denning DW. Invasive aspergillosis. Clin Infect Dis 1998; 26: the presence of a complete radiological response, while for 781–805. Offner et al,12 patients may relapse even in the absence of 2 Bow EJ, Loewen R, Cheang MS, Schacter B. Invasive fungal residual lesions. What is universally agreed is that a history disease in adults undergoing remission-induction therapy for acute myeloid leukemia: the pathogenetic role of the antileu- of IA is not an absolute contraindication to further chemo- 10,17–18 kemic regimen. Clin Infect Dis 1995; 21: 361–369. therapy and SCT. Ideally, patients needing further 3 Maertens J, Verhaegen J, Lagrou K et al.
Recommended publications
  • 012402 Voriconazole Compared with Liposomal Amphotericin B
    The New England Journal of Medicine Copyright © 2002 by the Massachusetts Medical Society VOLUME 346 J ANUARY 24, 2002 NUMBER 4 VORICONAZOLE COMPARED WITH LIPOSOMAL AMPHOTERICIN B FOR EMPIRICAL ANTIFUNGAL THERAPY IN PATIENTS WITH NEUTROPENIA AND PERSISTENT FEVER THOMAS J. WALSH, M.D., PETER PAPPAS, M.D., DREW J. WINSTON, M.D., HILLARD M. LAZARUS, M.D., FINN PETERSEN, M.D., JOHN RAFFALLI, M.D., SAUL YANOVICH, M.D., PATRICK STIFF, M.D., RICHARD GREENBERG, M.D., GERALD DONOWITZ, M.D., AND JEANETTE LEE, PH.D., FOR THE NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES MYCOSES STUDY GROUP* ABSTRACT NVASIVE fungal infections are important caus- Background Patients with neutropenia and per- es of morbidity and mortality among patients sistent fever are often treated empirically with am- receiving cancer chemotherapy or undergoing photericin B or liposomal amphotericin B to prevent bone marrow or stem-cell transplantation.1-3 invasive fungal infections. Antifungal triazoles offer IOver the past two decades, empirical antifungal ther- a potentially safer and effective alternative. apy with conventional amphotericin B or liposomal Methods In a randomized, international, multi- amphotericin B has become the standard of care in center trial, we compared voriconazole, a new sec- reducing invasive fungal infections in patients with ond-generation triazole, with liposomal amphoteri- neutropenia and persistent fever.4-9 Amphotericin B, cin B for empirical antifungal therapy. however, is associated with significant dose-limiting Results A total of
    [Show full text]
  • Voriconazole
    Drug and Biologic Coverage Policy Effective Date ............................................ 6/1/2020 Next Review Date… ..................................... 6/1/2021 Coverage Policy Number .................................. 4004 Voriconazole Table of Contents Related Coverage Resources Coverage Policy ................................................... 1 FDA Approved Indications ................................... 2 Recommended Dosing ........................................ 2 General Background ............................................ 2 Coding/Billing Information .................................... 4 References .......................................................... 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
    [Show full text]
  • Susceptibility of Filamentous Fungi to Voriconazole in Malaysia Tested by Sensititre Yeastone and CLSI Microdilution Methods
    Susceptibility of Filamentous Fungi to Voriconazole in Malaysia Tested by Sensititre YeastOne and CLSI Microdilution Methods Xue Ting Tan ( [email protected] ) National Institute of Health, Malaysia Stephanie Jane Ginsapu National Institute of Health, Malaysia Fairuz binti Amran National Institute of Health, Malaysia Salina binti Mohamed Sukur National Institute of Health, Malaysia Surianti binti Shukor National Institute of Health, Malaysia Research Article Keywords: Voriconazole, Sensititre, CLSI, Mould Posted Date: February 12th, 2021 DOI: https://doi.org/10.21203/rs.3.rs-199013/v1 License: This work is licensed under a Creative Commons Attribution 4.0 International License. Read Full License Page 1/15 Abstract Background: Voriconazole is a trizaole antifungal to treat fungal infection. In this study, the susceptibility pattern of voriconazole against lamentous fungi was studied using Sensititre® YeastOne and Clinical & Laboratory Standards Institute (CLSI) M38 broth microdilution method. Methods: The suspected cultures of Aspergillus niger, A. avus, A. fumigatus, A. versicolor, A. sydowii, A. calidoutus, A. creber, A. ochraceopetaliformis, A. tamarii, Fusarium solani, F. longipes, F. falciferus, F. keratoplasticum, Rhizopus oryzae, R. delemar, R. arrhizus, Mucor sp., Poitrasia circinans, Syncephalastrum racemosum and Sporothrix schenckii were received from hospitals. Their identication had been conrmed in our lab and susceptibility tests were performed using Sensititre® YeastOne and CLSI M38 broth microdilution method. The signicant differences between two methods were calculated using Wilcoxon Sign Rank test. Results: Mean of the minimum inhibitory concentrations (MIC) for Aspergillus spp. and Fusarium were within 0.25 μg/mL-2.00 μg/mL by two methods except A. calidoutus, F. solani and F. keratoplasticum.
    [Show full text]
  • Itraconazole (Sporonox ) & Voriconazole (Vfend )
    Itraconazole (Sporonox) & Voriconazole (Vfend) These are broad spectrum, anti-fungal agents that can be taken orally. They are very expensive approx $800- $1100/month). Although both these prescription medications are FDA approved for the treatment of mold or fungal infections, they do not have a specific indication for the treatment of fungal rhinosinusitis. Molds appear to be present in everyone's nasal and sinus passageways but in some individuals, the molds appear to cause disease. The explanation for this is unknown (See What is Rhinosinusitis?). As such, Insurers resist covering them for treatment of rhinosinusitis associated with the presence of molds. Itraconazole • Your liver enzymes will be monitored by periodically by blood tests. • Take your Itraconazole dose at the same time everyday. • Take your medication after a full meal. • Antacids can reduce absorption of this medication and if need be they should be taken at least 1 hour before or 2 hours after taking Itraconazole. • If you are taking stomach medication, make sure you drink cola beverage with the Itraconazole to help it become absorbed. • Report any signs or symptoms of unusual fatigue, anorexia, nausea and/or vomiting, jaundice (yellowing skin), dark urine, or pale stools. • Other potential side effects include elevated liver enzymes, gastrointestinal disorders, rash, hypertension, orthostatic hypertension, headache, malaise, myalgia, vasculitis, edema, and vertigo. • Contact your practitioner BEFORE beginning any new medications while taking Itraconazole. • Women should use effective measures to PREVENT pregnancy during and up to 2 months after finishing itraconazole. • Itraconazole should not be taken with a class of cholesterol-lowering drugs known as statins, unless your physicians has specifically told you to do so.
    [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]
  • VORICONAZOLE Persists, Consult Your Doctor
    may come back. If the infection worsens or should avoid driving, using machinery or VORICONAZOLE persists, consult your doctor. doing something that may be dangerous if your vision is impaired. Notify your doctor if Other NAMES: Vfend What should you do if you FORGET a your vision changes or if bright lights are dose? bothersome. WHY is this drug prescribed? If you miss a dose voriconazole, take it as What other PRECAUTIONS should you Voriconazole is an antifungal drug. It is used soon as possible. However, if it is time for follow while using this drug? to treat a variety of fungal infections (candida, your next dose, do not double the dose, just aspergillosis) in the mouth (like thrush), carry on with your regular schedule. Before starting voriconazole, please inform esophagus, lungs, blood and in other areas. your doctor if you have ever developed an What ADVERSE EFFECTS can this drug allergy to voriconazole or to similar drugs HOW should this drug be taken? cause? What should you do about them? [ketoconazole (Nizoral ), fluconazole (Diflucan ), itraconazole (Sporanox ). Also Voriconazole is available as 50 mg and 200 Voriconazole may cause some stomach notify your doctor if you have kidney, liver or mg tablets. During the first days of therapy, it upset, nausea, vomiting and loss of vision problems. can also be given by intravenous (I.V.: in the appetite . Some other potential adverse veins) injections. The intravenous injections effects are abdominal pain, diarrhea, and Certain drugs can increase or decrease the will be given over a 1 to 2 hour period, likely headache .
    [Show full text]
  • Voriconazole—A New Therapeutic Agent with an Extended Spectrum of Antifungal Activity J
    View metadata, citation and similar papers at core.ac.uk brought to you by CORE provided by Elsevier - Publisher Connector Voriconazole—a new therapeutic agent with an extended spectrum of antifungal activity J. P. Donnelly1 and B. E. De Pauw2 1Department of Haematology and 2Department of Blood Transfusion and Transplant Immunology, University Medical Center St Radboud, Nijmegen, the Netherlands ABSTRACT Voriconazole is a new antifungal agent that can be given orally and intravenously. It has proven efficacy for treating candidosis and invasive aspergillosis as well as other mould infections, such as those caused by Fusarium and Scedosporium spp. The drug is generally well tolerated. Keywords Voriconazole, antifungal treatment, invasive fungal infection Clin Microbiol Infect 2004; 10 (Suppl. 1): 107–117 INTRODUCTION Voriconazole was discovered in the late 1980s. The discovery process was started with the idea of developing an antifungal agent with a spec- trum of activity beyond that of fluconazole. Like fluconazole, voriconazole belongs to the triazole class of drugs (Fig. 1). It is relatively insoluble in water, so the intravenous formulation contains voriconazole in a sulphobutylether b-cyclodextrin (SBECD) solute to allow for parenteral adminis- Fig. 1. Structural relationship between voriconazole and tration. fluconazole. The clinical development programme included the largest-ever randomised controlled trial in the 250-fold more active against the fungal demethy- treatment of invasive aspergillosis. The findings lase enzyme than against mammalian P450- of this trial demonstrate the significantly superior dependent steroid hormone biosynthesis efficacy of a clinical regimen that starts with [1]. voriconazole, over standard therapy starting with amphotericin B deoxycholate. SPECTRUM OF ACTIVITY MECHANISM OF ACTION Voriconazole exhibits broad-spectrum activity at concentrations of £ 1mg⁄ L against the more Voriconazole selectively inhibits the fungal cyto- common fungal pathogens such as Candida spp.
    [Show full text]
  • Vfend, INN-Voriconazole
    SCIENTIFIC DISCUSSION This module reflects the initial scientific discussion for the approval of Vfend. For information on changes after approval please refer to module 8B. 1. Introduction This centralised procedure concerns Vfend film-coated tablets and powder for solution for infusion (10 mg/ml after reconstitution) with the new active antimycotic substance voriconazole. This new systemic antimycotic agent is a triazole derivative. N N N CH3 F OH F N N F voriconazole A new excipient sulphobutylether beta-cyclodextrin sodium (SBECD) is used in the parenteral formulation to enhance the solubility of voriconazole. Voriconazole is complexed with SBECD and the concentration of SBECD in the reconstituted voriconazole solution for injection is 160 mg/ml The approved indications include: • Treatment of invasive aspergillosis • Treatment of candidemia in non-neutropenic patients. • Treatment of fluconazole-resistant serious invasive Candida infections (including C. krusei) • Treatment of serious fungal infections caused by Scedosporium spp. and Fusarium spp. Posology: Intravenous Oral Patients 40 kg and above Patients less than 40 kg Loading Dose 6 mg/kg every 12 hours 400 mg every 12 hours 200 mg every 12 hours Regimen (for the first 24 hours) (for the first 24 hours) (for the first 24 hours) (first 24 hours) Maintenance Dose 4 mg/kg twice daily 200 mg twice daily 100 mg twice daily (after first 24 hours) Voriconazole is a novel triazole antifungal agent shown to have in vitro activity against Aspergillus and Candida species. Voriconazole represents a therapeutic alternative especially with regard to amphotericin B characterised by a nephrotoxicity of concern in clinical practice. 1/28 EMEA 2005 2.
    [Show full text]
  • Amphotericin B Amphocil
    Public Assessment Report for paediatric studies submitted in accordance with Article 45 of Regulation (EC) No1901/2006, as amended Amphotericin B Amphocil Abelcet DE/W/009/pdWS/001 Rapporteur: Germany Finalisation procedure (day 120): 24.11.2017 Amphotericin B DE/W/009/pdWS/001 Seite 1 TABLE OF CONTENTS I. Executive Summary ....................................................................................................... 4 II. RecommendatioN .......................................................................................................... 4 III. INTRODUCTION ............................................................................................................. 6 IV. SCIENTIFIC DISCUSSION .............................................................................................. 7 IV.1 Information on the pharmaceutical formulation used in the clinical studies .............. 7 IV.2 Non-clinical aspects ................................................................................................................... 9 IV.3 Clinical aspects .......................................................................................................................... 10 V. MEMBER STATES Overall Conclusion AND RECOMMENDATION ........................... 31 VI. List of Medicinal products and marketing authorisation holders involved ............. 33 Amphotericin B DE/W/009/pdWS/001 Page 2/33 ADMINISTRATIVE INFORMATION Invented name of the medicinal See section VI product(s): INN (or common name) of the active Amphotericin B substance(s):
    [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]
  • 1. NAME of the MEDICINAL PRODUCT Voriconazole Pfizer 50
    1. NAME OF THE MEDICINAL PRODUCT Voriconazole Pfizer 50 mg film-coated tablets Voriconazole Pfizer 200 mg film-coated tablets 2. QUALITATIVE AND QUANTITATIVE COMPOSITION Each tablet contains 50 or 200 mg voriconazole. Excipient with known effect Voriconazole Pfizer 50 mg film-coated tablets Each tablet contains 63.42 mg lactose monohydrate. Voriconazole Pfizer 200 mg film-coated tablets Each tablet contains 253.675 mg lactose monohydrate. For the full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Voriconazole Pfizer 50 mg film coated tablets. White to off-white, round tablet, debossed “Pfizer” on one side and “VOR50”on the reverse. Voriconazole Pfizer 200 mg film-coated tablets White to off-white, capsule-shaped tablet, debossed “Pfizer” on one side and “VOR200”on the reverse. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications Voriconazole Pfizer, is a broad-spectrum, triazole antifungal agent and is indicated in adults and children aged 2 years and above as follows: Treatment of invasive aspergillosis. Treatment of candidaemia in non-neutropenic patients. Treatment of fluconazole-resistant serious invasive Candida infections (including C. krusei). Treatment of serious fungal infections caused by Scedosporium spp. and Fusarium spp. Voriconazole Pfizer should be administered primarily to patients with progressive, possibly life-threatening infections. Prophylaxis of invasive fungal infections in high risk allogeneic hematopoietic stem cell transplant (HSCT) recipients. 1 4.2 Posology and method of administration Posology Electrolyte disturbances such as hypokalaemia, hypomagnesaemia and hypocalcaemia should be monitored and corrected, if necessary, prior to initiation and during voriconazole therapy (see section 4.4). Voriconazole Pfizer is also available as 200 mg powder for solution for infusion and 40 mg/ml powder for oral suspension.
    [Show full text]
  • Treatment of Fungal Infections in Adult Pulmonary and Critical Care Patients
    American Thoracic Society Documents An Official American Thoracic Society Statement: Treatment of Fungal Infections in Adult Pulmonary and Critical Care Patients Andrew H. Limper, Kenneth S. Knox, George A. Sarosi, Neil M. Ampel, John E. Bennett, Antonino Catanzaro, Scott F. Davies, William E. Dismukes, Chadi A. Hage, Kieren A. Marr, Christopher H. Mody, John R. Perfect, and David A. Stevens, on behalf of the American Thoracic Society Fungal Working Group THIS OFFICIAL STATEMENT OF THE AMERICAN THORACIC SOCIETY (ATS) WAS APPROVED BY THE ATS BOARD OF DIRECTORS, MAY 2010 CONTENTS immune-compromised and critically ill patients, including crypto- coccosis, aspergillosis, candidiasis, and Pneumocystis pneumonia; Introduction and rare and emerging fungal infections. Methods Antifungal Agents: General Considerations Keywords: fungal pneumonia; amphotericin; triazole antifungal; Polyenes echinocandin Triazoles Echinocandins The incidence, diagnosis, and clinical severity of pulmonary Treatment of Fungal Infections fungal infections have dramatically increased in recent years in Histoplasmosis response to a number of factors. Growing numbers of immune- Sporotrichosis compromised patients with malignancy, hematologic disease, Blastomycosis and HIV, as well as those receiving immunosupressive drug Coccidioidomycosis regimens for the management of organ transplantation or Paracoccidioidomycosis autoimmune inflammatory conditions, have significantly con- Cryptococcosis tributed to an increase in the incidence of these infections. Aspergillosis Definitive
    [Show full text]