DOCSLIB.ORG

Comparison of Isavuconazole and Other Azoles with Respect to Physicochemical and Patrice Larger Poster No

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Comparison of Isavuconazole and Other Azoles with Respect to Physicochemical and Patrice Larger Poster No Contact Information Comparison of Isavuconazole and Other Azoles with Respect to Physicochemical and Patrice Larger Poster No. Basilea Pharmaceutica International Ltd Pharmacokinetic Properties Affecting Tissue Penetration Grenzacherstrasse 487 P1734 PO Box 4005, Basel, Switzerland 1 1 1 Patrice Larger , Ulrike Wenzler and Anne Schmitt-Hoffmann Telephone: +41 61 606 1482 1Basilea Pharmaceutica International Ltd, Basel, Switzerland Email: [email protected] Introduction and Purpose Methods/Results Methods/Results Methods/Results • Isavuconazole is a broad-spectrum antifungal triazole administered as the water-soluble prodrug, isavuconazonium sulfate. • In a quantitative whole-body autoradiography (QWBA) study in healthy male Sprague-Dawley rats8, isavuconazole was: • Isavuconazonium sulfate has been approved by the U.S. Food and Drug Administration for the treatment of adults with invasive Comparison of physicochemical characteristics of isavuconazole and other azoles In vivo distribution characteristics of isavuconazole and other azoles aspergillosis (IA) and invasive mucormycosis, and by the European Commission for the treatment of adults with IA and those – Widely distributed in all tissues, within 0.5 h after a single dose IV bolus administration. with mucormycosis for whom amphotericin B is inappropriate.1,2 • Physicochemical properties: • Permeability and lipophilicity (LogD at • Polar surface area (PSA): • Pharmacokinetic properties and information regarding drug distribution of antifungal azoles from human and animal – Present in sanctuary sites, with concentrations higher than in blood, in absence of inflammation. pH 7.4*): studies: • A key determinant for clinically relevant efficacy of an antifungal drug is tissue penetration, which is dependent on its – Calculated in silico from – Calculated in • Brain (Cbrain:Cplasma = 1.86); Testes (Ctestes:Cplasma = 1.56); membrane permeability and is influenced by physicochemical parameters ( ).3 Calculated in GastroPlus v9.0.005 Figure 1 their respective structures. – MarvinSketch 5.4.0.1 – A literature search was conducted in EMBASE (Elsevier, Amsterdam, The Netherlands). Blood (Cblood:Cplasma = 1.07). using ADMET Predictor v7.2.0.0 – Structures were drawn in (ChemAxon, Budapest, • In a study of Wistar rats, after a single oral dose of either isavuconazonium sulfate (25 mg/kg Figure 1. Free drug concept and distribution: drug penetration and distribution in tissues (Simulations Plus, Lancaster, USA). • Search terms used (without further restriction): isavuconazole, voriconazole, itraconazole, posaconazole, Biovia Draw (Biovia, San Hungary). isavuconazole equivalent) or voriconazole (50 mg/kg), active drug concentrations were Permeability coefficient (P ) prediction fluconazole, pharmacology, pharmacokinetics, tissue, penetration, distribution, drug transporter, efflux pump, Diego, USA) and imported – eff measured in both brain and plasma using a validated liquid chromatography-mass spectrometry/ for intestinal permeability was used as a p-glycoprotein, and p-gp. as .mol files or .sdf files into mass spectrometry method.9 prediction software. general indicator of predicted • Articles and congress abstracts were considered. permeability. – Concentrations of both drugs in the brain paralleled those in plasma, with the maximum *Note: all azoles are very weak bases and are neutral at physiological concentration in brain approximately twice as high as that in plasma. pH (7–7.4); therefore, LogD = logP. 7.4 • Given the plasma half-life of 115 h in humans (Table 2), once-daily maintenance dosing of isavuconazole is expected to produce tissue levels that remain high and are more constant over Table 1. Physicochemical properties of antifungal azoles Table 2. Pharmacokinetic properties of antifungal azoles in humans time versus those achieved with twice-daily administration of voriconazole, which has a 6-h half-life. Pgp Molecular Polarity Permeability P-gp Plasma protein Lipophilicity t a V , L/kg Drug Molecular structure weighta PSAa,b P a,c Drug 1/2 Substrate binding, % ss Evidence of efficacy against CNS fungal infections LogD a,c eff (h) [Reference] (g/mol) (Å2) 7.4 (10-4 cm/s) [Reference] [Reference] Good tissue penetration in the brain is associated with positive treatment outcomes of Pe central nervous system (CNS) infection both in vivo and clinically. – Isavuconazole was effective in a non-clinical model of cryptococcal meningitis with good brain exposure measured in mice.10 Isavuconazole 437.5 88 3.6 4.0 Isavuconazole 110/115 No [4] 99.2–99.4 [5] 6 [5] – Clinical case reports support the clinical efficacy of isavuconazole for treatment of CNS fungal infections.11-13 C C C C b, plasma u, plasma u, tissue b, tissue • The Infectious Diseases Working Party (AGIHO) of the German Society of fu, plasma fu, tissue Haematology and Medical Oncology (DGHO) recommends isavuconazole for salvage treatment of CNS mucormycosis.14 Cplasma Ctissue Itraconazole 705.7 101 4.9 1.9 Itraconazole 34–42 Yes [6] 99.8 [3] 11 [3] C f f tissue u plasma u plasma Conclusions = Vss Vplasma tissue Cplasma fu tissue fu tissue • Isavuconazole has physicochemical properties that favour high permeability. Posaconazole 29/27 Yes [7] >98 [3] 7–25 [3] Cb, plasma, bound plasma concentration; Cb, tissue, bound tissue concentration; Cplasma, total plasma concentration; Ctissue, total tissue concentration; Cu, plasma, unbound plasma concentration; Posaconazole 700.8 112 4.4 1.9 Cu, tissue, unbound tissue concentration; fu, plasma, fraction unbound in plasma; fu, tissue, fraction unbound in tissue; Pe, permeability (passive diffusion across membranes); • Isavuconazole is not a substrate of efflux pumps, which can limit penetration to certain Pgp, P-glycoprotein (efflux pump transporter); V , plasma volume; V , apparent volume of distribution at steady state (PK parameter); V , tissue volume. plasma ss tissue tissues, including the brain. • Isavuconazole is extensively distributed in most organs and tissues, and it penetrates • Drug activity is dependent on free (unbound) drug concentration at the site of action (Cu, tissue). • Tissue penetration is dependent on membrane permeability. sanctuary-site organs, such as the brain and testes. • Taken together, these data suggest that isavuconazole could have clinical efficacy against – Physicochemical properties influence permeability. Voriconazole 349.3 76 2.1 4.5 Voriconazole 6 Nob 58 [3] 4.6 [3] • Lipophilicity increases permeability. fungal infections involving the CNS and other sanctuary sites. • Molecular weight and polarity decrease permeability. – Disease-specific alterations of membrane physiology (e.g., infections and inflammation) can alter permeability. References – Additional physiological factors can affect a drug’s ability to penetrate tissue, such as the tightness of the endothelium and 1. Astellas Pharma US Inc., CRESEMBA®. Cresemba (isavuconazonium sulfate) prescribing information. (Accessed 6 March, 2017 at http://www.accessdata.fda.gov/drugsatfda_docs/label/2015/207500Orig1s000lbl.pdf). the action of efflux pumps (e.g., P-glycoprotein [P-gp]), which actively transport the drug back to the plasma and can thus ® Fluconazole 306.3 81 0.8 4.1 Fluconazole 30 Nob 12 [3] 0.7 [3] 2. European Medicines Agency. CRESEMBA (isavuconazole). (Accessed 6 March, 2017 at http://www.ema.europa.eu/ema/index. decrease Cu, tissue. jsp?curl=pages/medicines/human/medicines/002734/human_med_001907.jsp&mid=WC0b01ac058001d124). 3. Felton T, et al. 2014. Clin Microbiol Rev. 27:68–88. 4. Yamazaki T, et al. 2017. Clin Pharmacol Drug Dev. 6:66–75. 5. Desai A, et al. 2016. Antimicrob Agents – Certain tissues (sanctuary sites, such as the brain or testes) combine a tight endothelium and high expression of efflux Chemother. 60:5483–5491. 6. Lestner J and Hope WW. 2013. Expert Opin Drug Metab Toxicol. 9:911–926. 7. Nagappan V and Deresinski pump transporters, which act as a significant barrier to drug penetration. S. 2007. Clin Infect Dis. 45:1610–1617. 8. Schmitt-Hoffmann A and Richter W. 22nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID); London, United Kingdom; 31 March, 2012; abstr. P863. 9. Schmitt-Hoffmann A, et al. IDWeek™ 2016; a b c aTerminal half-life derived from MHRC SPCs and were measured under specific conditions; itraconazole oral/IV with repeated dosing; posaconazole oral/IV 300 mg; • Tissue/plasma concentration ratio and volume of distribution are dependent on permeability and relative affinity (Figure 1). Predicted from structure with (MarvinSketch 5.4.0.1) or (ADMET Predictor v7.2.0.0). New Orleans, LA; 29 October, 2016; abstr. 1952. 10. Wiederhold NP, et al. 2016. Antimicrob Agents Chemother. 60:5600–5603. P , permeability coefficient; PSA, Polar Surface Area. isavuconazole oral/IV 400 mg; voriconazole oral 200 mg; fluconazole oral/IV. eff 11. Everson N, et al. 25th European Congress of Clinical Microbiology and Infectious Diseases (ECCMID); Copenhagen, Denmark; 25 April, b – At equilibrium, a drug freely permeates across membranes and Cu, tissue = Cu, plasma or AUCu, tissue = AUCu, plasma; therefore: No definite information found, not likely to be good substrates. 2015; abstr. P0231. 12. Peixoto D, et al. 2014. J Clin Microbiol. 52:1016–1019. 13. Thompson GR, 3rd, et al. 2016. Clin Infect Dis. MHRA SPC, Medicines & Healthcare products Regulatory Agency Summary of Product Characteristics; P-gp, P-glycoprotein; t1/2, terminal half-life; Vss, volume of distribution at 63:356–362. 14. Schmidt-Hieber M, et al. 2016. Ann Oncol.
Load more

Recommended publications
  • Comparative Evaluation of Isavuconazonium Sulfate
    Van Matre et al. Ann Clin Microbiol Antimicrob (2019) 18:13 https://doi.org/10.1186/s12941-019-0311-3 Annals of Clinical Microbiology and Antimicrobials RESEARCH Open Access Comparative evaluation of isavuconazonium sulfate, voriconazole, and posaconazole for the management of invasive fungal infections in an academic medical center Edward T. Van Matre1 , Shelby L. Evans2, Scott W. Mueller3, Robert MacLaren3, Douglas N. Fish3 and Tyree H. Kiser3,4* Abstract Background: Invasive fungal infections are a major cause of morbidity and mortality. Newer antifungals may provide similar efcacy with improved safety compared to older more established treatments. This study aimed to compare clinically relevant safety and efcacy outcomes in real world patients treated with isavuconazole, voriconazole, or posaconazole. Methods: This single center retrospective matched cohort study evaluated adults between January 2015 and Decem- ber 2017. The primary outcome was a composite safety analysis of antifungal related QTc prolongation, elevated liver function tests (> 5 times ULN), or any documented adverse drug event. Key secondary outcomes included: individual safety events, 30-day readmissions, magnitude of drug interactions with immunosuppressive therapy, and overall cost. Results: A total of 100 patients were included: 34 patients in the voriconazole group and 33 patients within each of the isavuconazole and posaconazole groups. The composite safety outcome occurred in 40% of the total cohort and was diferent between isavuconazole (24.2%), voriconazole (55.9%), and posaconazole (39.4%; p 0.028). Change in QTc (p < 0.01) and magnitude of immunosuppression dose reduction (p 0.029) were diferent between= the three groups. No diferences in mortality, length of stay, readmission, or infection= recurrence were observed between groups (p > 0.05 for all).
    [Show full text]
  • Antifungals, Oral
    Antifungals, Oral Therapeutic Class Review (TCR) July 13, 2018 No part of this publication may be reproduced or transmitted in any form or by any means, electronic or mechanical, including photocopying, recording, digital scanning, or via any information storage or retrieval system without the express written consent of Magellan Rx Management. All requests for permission should be mailed to: Magellan Rx Management Attention: Legal Department 6950 Columbia Gateway Drive Columbia, Maryland 21046 The materials contained herein represent the opinions of the collective authors and editors and should not be construed to be the official representation of any professional organization or group, any state Pharmacy and Therapeutics committee, any state Medicaid Agency, or any other clinical committee. This material is not intended to be relied upon as medical advice for specific medical cases and nothing contained herein should be relied upon by any patient, medical professional or layperson seeking information about a specific course of treatment for a specific medical condition. All readers of this material are responsible for independently obtaining medical advice and guidance from their own physician and/or other medical professional in regard to the best course of treatment for their specific medical condition. This publication, inclusive of all forms contained herein, is intended to be educational in nature and is intended to be used for informational purposes only. Send comments and suggestions to [email protected]. July 2018 Proprietary Information. Restricted Access – Do not disseminate or copy without approval. © 2004-2018 Magellan Rx Management. All Rights Reserved. FDA-APPROVED INDICATIONS Drug Manufacturer FDA-Approved Indication(s) for oral use clotrimazole generic .
    [Show full text]
  • Description Price NDC CABLE PULSE OX (4083) 0 DERMABOND(DNX12) (SEE MIKE) 0 HO-CEMENTED STEM SZ 16 71316216 10671.26 NECK METHA MOD
    Description Price NDC CABLE PULSE OX (4083) 0 DERMABOND(DNX12) (SEE MIKE) 0 HO-CEMENTED STEM SZ 16 71316216 10671.26 NECK METHA MOD. 130DEG./7.5 L NC077K 8451.29 NECK METHA MOD. 130DEG/7.5 L-R NC079K 8400.06 NEEDLE HOLDER WEBSTER P0405 0 POLYP ETRAP 00711099 1202.32 SET CLEANING BRUSHES 0 TIDISHIELD FRAMES/LENS 9210A-100 0 #1613 VENTILATOR CIR 20.01 #1627 VENTILATOR CIR 21.39 #9 WINDOW ENVELOPE(LAB) 0 * 0 ** 3A ANDROSTANEDIOL GLUCURONIDE 345.81 ** ALKALINE PHOSPHATASE (FRAC) 70.66 ** ALKALINE PHOSPHATASE (FRAC) 99.51 ** CSF3R EXON 14/17 MUTATION 787.47 ** FCM EACH ADDITIONAL MARKER 19.76 ** FECAL ALPHA-1 ANTIRYPSIN 183.16 ** FLOW CYTO INTER/REPT 2 TO 8 MARKERS 115.37 ** TRICYCLIC ANTIDEPRESSANTS QNT UR 227.87 ** URINE PHOSPHORUS ASSAY 70.66 **% DELTA 2 HR 0 **% DELTA 4 HR 0 **% DELTA 6 HR 0 **(RI ANTIBODY WESTERN BLOT ATHENA 246.62 *****UR MICROSCOPIC ONLY 61.69 *****URINALYSIS CANCELLATION NOTICE 0 *****URINALYSIS,BIOCHEM REQUEST 0 *****URINALYSIS,BIOCHEM REQUEST 0 ****2HR URINE CREATININE 70.66 ****CHLAMYDIA PNEUMONIAE AB IGG 79.32 ****HLA TYPING FOR CELIAC DISEASE 0 ****PLATELET AB SERUM 250.95 ****PLATELET PHERESIS LEUKO RED IRRAD 2787.85 ****VMA-SERUM 294.23 ***ANAPLASMA AMP DNA PROBE 469.17 ***BLEEDING TIME 62.02 ***HLA-B27 DNA TYPING 0 ***HSV AB IGM 197.59 ***IGG SERUM 172.72 ***IMMUNOGLOBULIN IGA1 SUBCLASS 57.69 ***IMMUNOGLOBULIN IGA2 SUBCLASS 57.69 ***LYME ANTIGEN DETECTION ELISA 167.67 ***LYME IGM ANTIBODY 204.8 ***MOLD ALLERGEN SCREEN 109.61 ***PATHOLOGY GROSS ONLY 0 **1 HR INCUBATION MIX PROGRESSIVE 89.43 **11 DEOXYCORTISOL
    [Show full text]
  • ASTELLAS Factsheet 1.Pdf
    Astellas is actively committed to the infectious disease field. Our infectious disease portfolio includes three classes of drugs: AmBisome® (amphotericin B) liposome for injection, CRESEMBA® (isavuconazonium sulfate), and MYCAMINE® (micafungin sodium) for injection. We continue to expand the knowledge base of this therapeutic area and empower physicians to make evidence-based clinical decisions. Our proud history of collaborating with clinical investigators has provided opportunities around the world to study compounds that have the potential to be significant breakthroughs and allows us to generate and publish key information about these advances. In fact, Astellas pioneered the empiric antifungal clinical trial and has performed some of the world’s largest clinical trials in fungal infections. AmBisome® is indicated for the following: • The incidence of some common adverse events was • Empirical therapy for presumed fungal infection in greater in patients taking AmBisome compared to febrile neutropenic patients patients taking Abelcet in the clinical study noted above • Treatment of Cryptococcal Meningitis in HIV-infected including: chest pain, hypocalcemia, hypomagnesemia, patients confusion, headache, and rash • Treatment of Aspergillus species, Candida species and/or Cryptococcus species infections refractory to Important Safety Information amphotericin B deoxycholate, or in patients where renal Despite significantly less nephrotoxicity observed at a dose impairment or unacceptable toxicity precludes the use range of 1.5–6.0 mg/kg/day compared to amphotericin B of amphotericin B deoxycholate deoxycholate at a dose range of 0.3–1.2 mg/kg/day in a • Treatment of visceral leishmaniasis; in randomized clinical trial, dose-limiting renal toxicity may still immunocompromised patients with visceral be observed with AmBisome.
    [Show full text]
  • Isavuconazonium
    Drug and Biologic Coverage Criteria Effective Date ............................................ 8/1/2020 Next Review Date… ..................................... 8/1/2021 Coverage Policy Number ................................ P0011 Isavuconazonium Table of Contents Related Coverage Resources Medical Necessity Criteria ................................... 1 FDA Approved Indications ................................... 2 Recommended Dosing ........................................ 2 Background .......................................................... 2 References .......................................................... 3 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
    [Show full text]
  • 207500S005,207501S004lbl.Pdf
    HIGHLIGHTS OF PRESCRIBING INFORMATION • Infusion-related reactions were reported during intravenous These highlights do not include all the information needed to use administration of CRESEMBA. Discontinue the infusion if these CRESEMBA® safely and effectively. See full prescribing information for reactions occur. (5.2) CRESEMBA®. • Hypersensitivity Reactions: Serious hypersensitivity and severe skin CRESEMBA® (isavuconazonium sulfate) capsules, for oral use reactions, such as anaphylaxis or Stevens Johnson syndrome, have been CRESEMBA® (isavuconazonium sulfate) for injection, for intravenous reported during treatment with other azole antifungal agents. use Discontinue CRESEMBA for exfoliative cutaneous reactions. (5.3) Initial U.S. Approval: 2015 • Embryo-Fetal Toxicity: CRESEMBA may cause fetal harm when ------------------------RECENT MAJOR CHANGES----------------------------­ administered to a pregnant woman. Advise pregnant women of the Warnings and Precautions, Embryo-Fetal Toxicity (5.4) 11/2019 potential risk to the fetus. Advise females of reproductive potential to ---------------------------INDICATIONS AND USAGE---------------------------­ use an effective method of contraception. (5.4, 8.1, 8.3) CRESEMBA® is an azole antifungal indicated for use in the treatment of: • Drug Interactions: Review patient’s concomitant medications. Several • Invasive aspergillosis. (1.1) drugs may significantly alter isavuconazole concentrations. Isavuconazole may alter concentrations of several drugs. (5.5, 7, 12.3) • Invasive mucormycosis. (1.2)
    [Show full text]
  • Analysis of US FDA-Approved Drugs Containing Sulfur Atoms
    Top Curr Chem (Z) (2018) 376:5 https://doi.org/10.1007/s41061-018-0184-5 REVIEW Analysis of US FDA‑Approved Drugs Containing Sulfur Atoms Kevin A. Scott1,2 · Jon T. Njardarson1 Received: 20 November 2017 / Accepted: 5 January 2018 / Published online: 22 January 2018 © Springer International Publishing AG, part of Springer Nature 2018 Abstract In this review, we discuss all sulfur-containing FDA-approved drugs and their structures. The second section of the review is dedicated to structural analy- sis and is divided into 14 subsections, each focusing on one type of sulfur-contain- ing moiety. A concise graphical representation of each class features drugs that are organized on the basis of structural similarity, evolutionary relevance, and medical indication. This review ofers a unique and comprehensive overview of the struc- tural features of all sulfur-containing FDA-approved drugs to date. Keywords Sulfonamide · Thioether · Sulfoxide · Sulfone · Sulfate · Sulfur heterocycle Abbreviations 6-APA 6-Aminopenicillanic acid ADP Adenosine diphosphate cGMP Cyclic guanosine monophosphate COX-2 Cyclooxygenase-2 GERD Gastroesophageal refux disease GPCR G protein-coupled receptor HIV Human immunodefciency virus mRNA Messenger RNA NSAID Nonsteroidal anti-infammatory drugs SMN1 Survival motor neuron 1 This article is part of the Topical Collection “Sulfur Chemistry”, edited by Xuefeng Jiang. * Jon T. Njardarson [email protected] 1 Department of Chemistry and Biochemistry, University of Arizona, Tucson, AZ 85721, USA 2 Department of Pharmacology
    [Show full text]
  • CRESEMBA (Isavuconazonium Sulfate) Is the Prodrug of Isavuconazole, an Azole Antifungal Drug
    HIGHLIGHTS OF PRESCRIBING INFORMATION • Infusion-related reactions were reported during intravenous administration These highlights do not include all the information needed to use of CRESEMBA. Discontinue the infusion if these reactions occur. (5.2) CRESEMBA® safely and effectively. See full prescribing information for • Hypersensitivity Reactions: Anaphylactic reactions, with fatal outcome, CRESEMBA®. have been reported during treatment with CRESEMBA. Discontinue CRESEMBA if a patient experiences an anaphylactic reaction. Serious CRESEMBA® (isavuconazonium sulfate) capsules, for oral use hypersensitivity and severe skin reactions, such as anaphylaxis or Stevens- CRESEMBA® (isavuconazonium sulfate) for injection, for intravenous Johnson syndrome, have been reported during treatment with other azole use antifungal agents. Discontinue CRESEMBA for exfoliative cutaneous Initial U.S. Approval: 2015 reactions. (5.3) • Embryo-Fetal Toxicity: CRESEMBA may cause fetal harm when -------------------------- RECENT MAJOR CHANGES -------------------------- administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use Dosage and Administration, Preparation Instructions for the Nasogastric Tube an effective method of contraception. (5.4, 8.1, 8.3) Administration of the Injection Formulation (2.5) 04/2021 • Drug Interactions: Review patient’s concomitant medications. Several drugs may significantly alter isavuconazole concentrations. Isavuconazole Warnings and Precautions,
    [Show full text]
  • Dosing & Administration Guide
    For first-line treatment of invasive aspergillosis and invasive mucormycosis in adults Dosing & administration guide INDICATIONS AND USAGE CRESEMBA® (isavuconazonium sulfate) is an azole antifungal indicated for patients 18 years of age and older for the treatment of invasive aspergillosis and invasive mucormycosis. Specimens for fungal culture and other relevant laboratory studies (including histopathology) to isolate and identify causative organism(s) should be obtained prior to initiating antifungal therapy. Therapy may be instituted before the results of the cultures and other laboratory studies are known. However, once these results become available, antifungal therapy should be adjusted accordingly. IMPORTANT SAFETY INFORMATION CONTRAINDICATIONS • CRESEMBA is contraindicated in persons with known hypersensitivity to isavuconazole • Coadministration of strong CYP3A4 inhibitors, such as ketoconazole or high-dose ritonavir (400 mg every 12 hours), with CRESEMBA is contraindicated because strong CYP3A4 inhibitors can significantly increase the plasma concentration of isavuconazole Please see additional Important Safety Information throughout brochure. Click here for full Prescribing Information for CRESEMBA and refer to CRESEMBA.com. For first-line treatment of invasive aspergillosis and invasive mucormycosis in adults Dosage formulations and strengths1 CRESEMBA® (isavuconazonium sulfate) for injection • CRESEMBA for injection is supplied in a single-dose vial as a sterile lyophilized white to yellow powder • Each single-dose vial of
    [Show full text]
  • Brain Penetration of Isavuconazole Following Single Dose Oral Administration to Wistar Rats Laura L
    1952 Contact information Brain Penetration of Isavuconazole Following Single Dose Oral Administration to Wistar Rats Laura L. Kovanda Astellas Pharma Global Development, Inc. 1 2 3 3 1 1 Astellas Way Anne-Hortense Schmitt-Hoffmann , Marlowe J. Schneidkraut , Nkechi Azie *, Robert Townsend , Jochen Spickermann Northbrook, IL, USA Telephone: +1 224 205 5962 1 2 3 Basilea Pharmaceutica International Ltd., Basel, Switzerland; Astellas Research Institute of America, Northbrook, IL, USA; Astellas Pharma Global Development, Inc., Northbrook, IL, USA; *At time of study Email: [email protected] • The concentrations of isavuconazole in brain paralleled those in Figure 2. Mean voriconazole concentrations (+SD) in Wistar rats ABSTRACT METHODS plasma, with the maximum concentration in brain approximately following a single oral dose of 50 mg/kg. (A) Lin/Log scale CONCLUSIONS double that observed in plasma (average individual brain/plasma (B) Lin/Lin scale Background: Area under the curve (AUC) has been reported as the • Two groups of 24 non-fasting, non-infected male Wistar rats concentration ratio, 1.8; coefficient of variation [CV], 16%) (Figure 1B). A 1E+05 Brain (ng/g) • Isavuconazole demonstrated efficient brain pharmacokinetic/pharmacodynamic driver for treatment efficacy of (297–352 g; Harlan, The Netherlands) were used; Plasma (ng/mL) triazole antifungal agents. Isavuconazole was evaluated in vivo in rats after penetration in rats. – Animal procedures and handling complied with all applicable • Plasma concentrations of voriconazole following a single oral p.o. administration (as isavuconazonium sulfate) to determine plasma and protocols and licenses; animals were individually housed in dose were variable, with no clear maximum observed within 8 h 1E+04 – Ratios of maximum isavuconazole concentrations brain tissue concentrations.
    [Show full text]
  • Perioperative Medication Management - Adult/Pediatric - Inpatient/Ambulatory Clinical Practice Guideline
    Effective 6/11/2020. Contact [email protected] for previous versions. Perioperative Medication Management - Adult/Pediatric - Inpatient/Ambulatory Clinical Practice Guideline Note: Active Table of Contents – Click to follow link INTRODUCTION........................................................................................................................... 3 SCOPE....................................................................................................................................... 3 DEFINITIONS .............................................................................................................................. 3 RECOMMENDATIONS ................................................................................................................... 4 METHODOLOGY .........................................................................................................................28 COLLATERAL TOOLS & RESOURCES..................................................................................................31 APPENDIX A: PERIOPERATIVE MEDICATION MANAGEMENT .................................................................32 APPENDIX B: TREATMENT ALGORITHM FOR THE TIMING OF ELECTIVE NONCARDIAC SURGERY IN PATIENTS WITH CORONARY STENTS .....................................................................................................................58 APPENDIX C: METHYLENE BLUE AND SEROTONIN SYNDROME ...............................................................59 APPENDIX D: AMINOLEVULINIC ACID AND PHOTOTOXICITY
    [Show full text]
  • Review Article Candida Infections, Causes, Targets, and Resistance Mechanisms: Traditional and Alternative Antifungal Agents
    Hindawi Publishing Corporation BioMed Research International Volume 2013, Article ID 204237, 13 pages http://dx.doi.org/10.1155/2013/204237 Review Article Candida Infections, Causes, Targets, and Resistance Mechanisms: Traditional and Alternative Antifungal Agents Claudia Spampinato1,2 and Darío Leonardi3,4 1 Departamento de Qu´ımica Biologica,´ Facultad de Ciencias Bioqu´ımicas y Farmaceuticas,´ Universidad Nacional de Rosario (UNR), Suipacha 531, 2000 Rosario, Argentina 2 Centro de Estudios Fotosinteticos´ y Bioqu´ımicos (CEFOBI, UNR-CONICET), Suipacha 531, 2000 Rosario, Argentina 3 Departamento de Tecnolog´ıa Farmaceutica,´ Facultad de Ciencias Bioqu´ımicas y Farmaceuticas,´ Universidad Nacional de Rosario (UNR), Suipacha 531, 2000 Rosario, Argentina 4 Instituto de Qu´ımica Rosario (IQUIR, UNR-CONICET), Suipacha 531, 2000 Rosario, Argentina Correspondence should be addressed to Dar´ıo Leonardi; [email protected] Received 8 April 2013; Revised 6 June 2013; Accepted 6 June 2013 Academic Editor: Abdelwahab Omri Copyright © 2013 C. Spampinato and D. Leonardi. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The genus Candida includes about 200 different species, but only a few species are human opportunistic pathogens and cause infections when the host becomes debilitated or immunocompromised. Candida infections can be superficial or invasive. Superficial infections often affect the skin or mucous membranes and can be treated successfully with topical antifungal drugs. However, invasive fungal infections are often life-threatening, probably due to inefficient diagnostic methods and inappropriate initial antifungal therapies. Here, we briefly review our current knowledge of pathogenic species of the genus Candida and yeast infection causes and then focus on current antifungal drugs and resistance mechanisms.
    [Show full text]