DOCSLIB.ORG

Important Drug Information

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Important Drug Information Important Drug Information Subject: Temporary importation of Doxorubicin Hydrochloride 50 mg Powder for Injection (50 mg/vial) to address drug shortage issue May 2016 Dear Health Care Provider, Due to the current critical shortage of Doxorubicin Hydrochloride for Injection, USP in the United States (U.S.) market, Hospira, Inc., a Pfizer company (Hospira), is coordinating with the U.S. Food and Drug Administration (FDA) to increase the availability of the drug. Hospira has initiated temporary importation of non-U.S. approved product, Doxorubicin Hydrochloride 50 mg Powder for Injection from Hospira Limited, United Kingdom (Hospira Limited): Lot DO21502A, expiration 12/2017. The Doxorubicin Hydrochloride 50 mg Powder for Injection from Hospira Limited is manufactured by Zydus Hospira Oncology Private Limited (ZHOPL) in Ahmedabad, India, at an FDA-inspected facility that is in compliance with current good manufacturing practice requirements. At this time, no other entity except Hospira Limited or their distributor Hospira is authorized by the FDA to import or distribute Doxorubicin Hydrochloride 50 mg Powder for Injection in the U.S. FDA has not approved Hospira Limited’s Doxorubicin Hydrochloride 50 mg Powder for Injection (50 mg/vial) product in the U.S. Effective immediately, and during this temporary period, Hospira will offer the following presentation of Doxorubicin Hydrochloride for Injection: Product Strength Size Marketing Authorization # Doxorubicin Hydrochloride PL 4515/0073 50 mg/vial Box of 1 vial 50 mg Powder for Injection (United Kingdom) The barcode used for Hospira Limited’s non-U.S. approved Doxorubicin Hydrochloride 50 mg Powder for Injection is an international pharmaceutical manufacturing code and may not be appropriately recognized by scanning systems used in the U.S. Institutions should confirm the barcode systems do not provide incorrect information when the product is scanned. Alternative procedures should be followed to assure that the correct drug product is being used and administered to individual patients. © 2016 Hospira, Inc., a Pfizer company, 275 North Field Drive, Lake Forest, IL 60045 PP-HSP-USA-0096 -April 2016 1 of 13 It is important to note that there are substantive differences in the format and content of the labeling between the U.S.-approved Doxorubicin Hydrochloride for Injection, USP and the Hospira Limited’s Doxorubicin Hydrochloride 50 mg Powder for Injection. The product comparison tables attached highlight the differences between the reference listed drug (RLD) Doxorubicin Hydrochloride for Injection, USP and Hospira Limited’s non-U.S. approved Doxorubicin Hydrochloride 50 mg Powder for Injection. This letter and the attachments are not intended as a complete description of the benefits and risks related to the use of Doxorubicin Hydrochloride 50 mg Powder for Injection. Please refer to the package insert for the FDA-approved Doxorubicin Hydrochloride for Injection, USP for full prescribing information. To place an order, or if you have any questions, customers can contact Hospira directly by calling Customer Care at 1-877-946-7747 (Monday – Friday, 7AM-6PM CDT). Hospira will make reasonable attempts to fill your orders. Hospira will be closely monitoring the distribution of Doxorubicin Hydrochloride 50 mg Powder for Injection to help manage supply. For clinical inquiries, please contact Hospira Medical Communications at 1-800-615-0187 (available 24 hours a day/7 days per week), or email at [email protected]. To report adverse events or quality problems associated with the use of this product, please call Hospira Global Complaint Management at 1-800-441-4100 (Monday – Friday, 8AM-5PM CDT), or email at [email protected]. Adverse reactions or quality problems experienced with the use of this product may be reported to the FDA's MedWatch Adverse Event Reporting program either online, by regular mail or by fax. Complete and submit the report Online: www.fda.gov/medwatch/report.htm. Regular Mail or Fax: Download form www.fda.gov/MedWatch/getforms.htm or call 1- 800-332-1088 to request a reporting form, then complete and return to the address on the pre-addressed form, or submit by fax to 1-800-FDA-0178 (1-800-332-0178). For Full U.S.-approved Prescribing Information for Doxorubicin Hydrochloride for Injection, including the BOXED WARNING, please visit: http://www.accessdata.fda.gov/spl/data/bb405a38-3e4e-49af-b30d-fb728f209022/bb405a38- 3e4e-49af-b30d-fb728f209022.xml For Full Prescribing Information for Hospira Limited’s product, please visit: http://www.pfizerinjectables.com/sites/default/files/doxorubicinSmPC-HospiraUK.pdf © 2016 Hospira, Inc., a Pfizer company, 275 North Field Drive, Lake Forest, IL 60045 PP-HSP-USA-0096 -April 2016 2 of 13 Product Vial and Carton Comparison Table Doxorubicin Hydrochloride for Injection, USP- Doxorubicin Hydrochloride 50 mg Powder for doxorubicin hydrochloride injection, powder, Injection – Hospira Limited Vial Label lyophilized, for solution – Reference Listed Drug (RLD) (Mylan Institutional LLC) Vial Label Not Available Doxorubicin Hydrochloride for Injection, USP- Doxorubicin Hydrochloride 50 mg Powder for doxorubicin hydrochloride injection, powder, Injection – Hospira Limited Carton Label lyophilized, for solution – Reference Listed Drug (RLD) (Mylan Institutional LLC) Carton Label © 2016 Hospira, Inc., a Pfizer company, 275 North Field Drive, Lake Forest, IL 60045 PP-HSP-USA-0096 -April 2016 4 of 13 Product Label Comparison Table Doxorubicin Hydrochloride for Injection, USP - Doxorubicin Hydrochloride 50 mg Powder for doxorubicin hydrochloride injection, powder, Injection – Hospira Limited lyophilized, for solution – Reference Listed Drug (RLD) (Mylan Institutional, LLC) BOXED WARNING WARNING: CARDIOMYOPATHY, SECONDARY MALIGNANCIES, EXTRAVASATION AND TISSUE NECROSIS and SEVERE MYELOSUPPRESSION Cardiomyopathy: Myocardial damage, including acute left ventricular failure can occur with doxorubicin hydrochloride. The risk of cardiomyopathy is proportional to the cumulative exposure with incidence rates from 1% to 20% for cumulative doses ranging from 300 mg/m2 to 500 mg/m2 when doxorubicin hydrochloride is administered every 3 weeks. The risk of cardiomyopathy is further increased with concomitant cardiotoxic therapy. Assess LVEF before and regularly during and after treatment with doxorubicin hydrochloride [see Warnings and Precautions (5.1)]. Secondary Malignancies : Secondary acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS) occur at a higher incidence in patients treated with anthracyclines, including doxorubicin hydrochloride [see Warnings and Precautions (5.2)]. Extravasation and Tissue Necrosis : Extravasation of doxorubicin hydrochloride can result in severe local tissue injury and necrosis requiring wide excision of the affected area and skin grafting. Immediately terminate the drug and apply ice to the affected area [see Warnings and Precautions (5.3)]. Severe myelosuppression resulting in serious infection, septic shock, requirement for transfusions , hospitalization, and death may occur [see Warnings and Precautions (5.4)]. Indications and contraindications Doxorubicin hydrochloride, USP is an anthracycline Therapeutic indications topoisomerase II inhibitor indicated: Doxorubicin has been used successfully in the treatment as a component of multiagent adjuvant of neoplastic conditions such as acute leukaemia, soft chemotherapy for treatment of women with axillary tissue and osteogenic sarcomas, breast carcinoma, lymph node involvement following resection of lymphomas, bronchogenic (lung) carcinoma. It has also primary breast cancer. been used in the treatment of paediatric malignancy. for the treatment of: acute lymphoblastic leukemia, Doxorubicin is frequently used in combination acute myeloblastic leukemia, Hodgkin lymphoma, chemotherapy regimen involving other cytotoxic drugs. Non-Hodgkin lymphoma, metastatic breast cancer, Doxorubicin can be used in the treatment of metastatic Wilms' tumor, metastatic non-metastatic transitional cell carcinoma, carcinoma in neuroblastoma,, metastatic soft tissue sarcoma, situ and papillary tumours of the bladder, by intravesical metastatic bone sarcomas, metastatic ovarian administration. carcinoma, metastatic transitional cell bladder carcinoma, metastatic thyroid carcinoma, metastatic © 2016 Hospira, Inc., a Pfizer company, 275 North Field Drive, Lake Forest, IL 60045 PP-HSP-USA-0096 -April 2016 5 of 13 Product Label Comparison Table gastric carcinoma, metastatic bronchogenic carcinoma. Contraindications Doxorubicin hydrochloride is contraindicated in Hypersensitivity to doxorubicin or any of the excipients. patients with: Severe myocardial insufficiency [see Warnings and Dosage should not be repeated in cases of bone marrow Precautions (5.1)] depression or buccal ulceration or buccal burning Recent (occurring within the past 4-6 weeks) sensation, which can precede ulceration. myocardial infarction [see Warnings and Precautions (5.1)] Severe persistent drug-induced myelosuppression [see Warnings and Precautions (5.4)] Severe hepatic impairment (defined as Child Pugh Class C or serum bilirubin level greater than 5 mg/dL) [see Warnings and Precautions (5.5)] Severe hypersensitivity reaction to doxorubicin hydrochloride including anaphylaxis [see Adverse Reactions (6.2)] Dosage and Administration Recommended Dose Intravenous administration Adjuvant Breast Cancer When used as a single agent, the recommended dosage 2 The recommended dose of doxorubicin
Load more

Recommended publications
  • PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects
    International Journal of Molecular Sciences Review PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects Rosalin Mishra , Hima Patel, Samar Alanazi , Mary Kate Kilroy and Joan T. Garrett * Department of Pharmaceutical Sciences, College of Pharmacy, University of Cincinnati, Cincinnati, OH 45267-0514, USA; [email protected] (R.M.); [email protected] (H.P.); [email protected] (S.A.); [email protected] (M.K.K.) * Correspondence: [email protected]; Tel.: +1-513-558-0741; Fax: +1-513-558-4372 Abstract: The phospatidylinositol-3 kinase (PI3K) pathway is a crucial intracellular signaling pathway which is mutated or amplified in a wide variety of cancers including breast, gastric, ovarian, colorectal, prostate, glioblastoma and endometrial cancers. PI3K signaling plays an important role in cancer cell survival, angiogenesis and metastasis, making it a promising therapeutic target. There are several ongoing and completed clinical trials involving PI3K inhibitors (pan, isoform-specific and dual PI3K/mTOR) with the goal to find efficient PI3K inhibitors that could overcome resistance to current therapies. This review focuses on the current landscape of various PI3K inhibitors either as monotherapy or in combination therapies and the treatment outcomes involved in various phases of clinical trials in different cancer types. There is a discussion of the drug-related toxicities, challenges associated with these PI3K inhibitors and the adverse events leading to treatment failure. In addition, novel PI3K drugs that have potential to be translated in the clinic are highlighted. Keywords: cancer; PIK3CA; resistance; PI3K inhibitors Citation: Mishra, R.; Patel, H.; Alanazi, S.; Kilroy, M.K.; Garrett, J.T.
    [Show full text]
  • Personal Radiation Monitoring
    Personal Radiation Monitoring Tim Finney 2020 Radiation monitoring Curtin staff and students who work with x-ray machines, neutron generators, or radioactive substances are monitored for exposure to ionising radiation. The objective of radiation monitoring is to ensure that existing safety procedures keep radiation exposure As Low As Reasonably Achievable (ALARA). Personal radiation monitoring badges Radiation exposure is measured using personal radiation monitoring badges. Badges contain a substance that registers how much radiation has been received. Here is the process by which a user’s radiation dose is measured: 1. The user is given a badge to wear 2. The user wears the badge for a set time period (usually three months) 3. At the end of the set time, the user returns the badge 4. The badge is sent away to be read 5. A dose report is issued. These steps are repeated until monitoring is no longer required. Badges are supplied by a personal radiation monitoring service provider. Curtin uses a service provider named Landauer. In addition to user badges, the service provider sends control badges that are kept on site in a safe place away from radiation sources. The service provider reads each badge using a process that extracts a signal from the substance contained in the badge to obtain a dose measurement. (Optically stimulated luminescence is one such process.) The dose received by the control badge is subtracted from the user badge reading to obtain the user dose during the monitoring period. Version 1.0 Uncontrolled document when printed Health and Safety Page 1 of 7 A personal radiation monitoring badge Important Radiation monitoring badges do not protect you from radiation exposure.
    [Show full text]
  • August 2019: Additions and Deletions to the Drug Product List
    Prescription and Over-the-Counter Drug Product List 39TH EDITION Cumulative Supplement Number 08 : August 2019 ADDITIONS/DELETIONS FOR PRESCRIPTION DRUG PRODUCT LIST ACETAMINOPHEN; BENZHYDROCODONE HYDROCHLORIDE TABLET;ORAL APADAZ >D> + KVK TECH INC 325MG;EQ 8.16MG BASE N 208653 003 Jan 04, 2019 Aug CHRS >A> +! 325MG;EQ 8.16MG BASE N 208653 003 Jan 04, 2019 Aug CHRS ACETAMINOPHEN; CODEINE PHOSPHATE TABLET;ORAL ACETAMINOPHEN AND CODEINE PHOSPHATE >A> AA ELITE LABS INC 300MG;15MG A 212418 001 Sep 10, 2019 Aug NEWA >A> AA 300MG;30MG A 212418 002 Sep 10, 2019 Aug NEWA >A> AA 300MG;60MG A 212418 003 Sep 10, 2019 Aug NEWA ACETAMINOPHEN; OXYCODONE HYDROCHLORIDE TABLET;ORAL OXYCODONE AND ACETAMINOPHEN >D> AA CHEMO RESEARCH SL 325MG;5MG A 207574 001 Dec 13, 2016 Aug CAHN >A> AA HALO PHARM CANADA 325MG;5MG A 207834 001 Aug 15, 2019 Aug NEWA >A> AA 325MG;7.5MG A 207834 002 Aug 15, 2019 Aug NEWA >A> AA 325MG;10MG A 207834 003 Aug 15, 2019 Aug NEWA >A> AA XIROMED 325MG;5MG A 207574 001 Dec 13, 2016 Aug CAHN ACYCLOVIR CAPSULE;ORAL ACYCLOVIR >A> AB CADILA 200MG A 204313 001 Mar 25, 2016 Aug CAHN >D> AB ZYDUS PHARMS 200MG A 204313 001 Mar 25, 2016 Aug CAHN >D> OINTMENT;OPHTHALMIC >D> AVACLYR >D> +! FERA PHARMS LLC 3% N 202408 001 Mar 29, 2019 Aug DISC >A> + @ 3% N 202408 001 Mar 29, 2019 Aug DISC OINTMENT;TOPICAL ACYCLOVIR >A> AB APOTEX INC 5% A 210774 001 Sep 06, 2019 Aug NEWA >D> AB PERRIGO UK FINCO 5% A 205659 001 Feb 20, 2019 Aug DISC >A> @ 5% A 205659 001 Feb 20, 2019 Aug DISC ALBENDAZOLE TABLET;ORAL ALBENDAZOLE >A> AB STRIDES PHARMA 200MG A 210011
    [Show full text]
  • Induction with Mitomycin C, Doxorubicin, Cisplatin And
    British Journal of Cancer (1999) 80(12), 1962–1967 © 1999 Cancer Research Campaign Article no. bjoc.1999.0627 Induction with mitomycin C, doxorubicin, cisplatin and maintenance with weekly 5-fluorouracil, leucovorin for treatment of metastatic nasopharyngeal carcinoma: a phase II study RL Hong1, TS Sheen2, JY Ko2, MM Hsu2, CC Wang1 and LL Ting3 Departments of 1Oncology, 2Otolaryngology and 3Radiation Therapy, National Taiwan University Hospital, National Taiwan University, No. 7, Chung-Shan South Road, Taipei 10016, Taiwan Summary The combination of cisplatin and 5-fluorouracil (5-FU) (PF) is the most popular regimen for treating metastatic nasopharyngeal carcinoma (NPC) but it is limited by severe stomatitis and chronic cisplatin-related toxicity. A novel approach including induction with mitomycin C, doxorubicin and cisplatin (MAP) and subsequent maintenance with weekly 5-FU and leucovorin (FL) were designed with an aim to reduce acute and chronic toxicity of PF. Thirty-two patients of NPC with measurable metastatic lesions in the liver or lung were entered into this phase II trial. Mitomycin C 8 mg m–2, doxorubicin 40 mg m–2 and cisplatin 60 mg m–2 were given on day 1 every 3 weeks as initial induction. After either four courses or remission was achieved, patients received weekly dose of 5-FU 450 mg m–2 and leucovorin 30 mg m–2 for maintenance until disease progression. With 105 courses of MAP given, 5% were accompanied by grade 3 and 0% were accompanied by grade 4 stomatitis. The dose-limiting toxicity of MAP was myelosuppression. Forty per cent of courses had grade 3 and 13% of courses had grade 4 leukopenia.
    [Show full text]
  • And Cisplatin-Resistant Ovarian Cancer
    Vol. 2, 607–610, July 2003 Molecular Cancer Therapeutics 607 Alchemix: A Novel Alkylating Anthraquinone with Potent Activity against Anthracycline- and Cisplatin-resistant Ovarian Cancer Klaus Pors, Zennia Paniwnyk, mediated stabilization of the topo II-DNA-cleavable complex Paul Teesdale-Spittle,1 Jane A. Plumb, and resulting in inhibition of poststrand passage DNA religa- Elaine Willmore, Caroline A. Austin, and tion (1). This event is not lethal per se but initiates a cascade 2 Laurence H. Patterson of events leading to cell death (2). Anthraquinones, as ex- Department of Pharmaceutical and Biological Chemistry, The School of emplified by mitoxantrone, are topo II inhibitors with proven Pharmacy, University of London, London WC1N 1AX, United Kingdom [K. P., L. H. P.]; Department of Pharmacy, De Montfort University, success for the treatment of advanced breast cancer, non- Leicester LE1 9BH, United Kingdom [Z. P., P. T. S.]; Cancer Research Hodgkin’s lymphoma, and acute leukemia (3). Intercalation is UK Department of Medical Oncology, University of Glasgow, Glasgow a crucial part of topo II inhibition by cytotoxic anthraquinones G61 1BD, United Kingdom [J. A. P.]; and School of Cell and Molecular Biosciences, The Medical School, University of Newcastle upon Tyne, with high affinity for DNA (4). It is likely that the potent Newcastle upon Tyne NE2 4HH, United Kingdom [E. W., C. A. A.] cytotoxicity of anthraquinones is related to their slow rate of dissociation from DNA, the kinetics of which favors long- term trapping of the topo-DNA complexes (5). However, Abstract currently available DNA intercalators at best promote a tran- Chloroethylaminoanthraquinones are described with sient inhibition of topo II, because the topo-drug-DNA ter- intercalating and alkylating capacity that potentially nary complex is reversed by removal of the intracellular drug covalently cross-link topoisomerase II (topo II) to DNA.
    [Show full text]
  • A Comparison of Early Intensive Methotrexate/Mercaptopurine With
    Leukemia (2001) 15, 1038–1045 2001 Nature Publishing Group All rights reserved 0887-6924/01 $15.00 www.nature.com/leu A comparison of early intensive methotrexate/mercaptopurine with early intensive alternating combination chemotherapy for high-risk B-precursor acute lymphoblastic leukemia: a Pediatric Oncology Group phase III randomized trial SJ Lauer1, JJ Shuster2, DH Mahoney Jr3, N Winick4, S Toledano5, L Munoz5, G Kiefer6, JD Pullen7, CP Steuber3 and BM Camitta6 1Emory University School of Medicine, Atlanta, GA; 2Pediatric Oncology Group Statistical Office and Department of Statistics, University of Florida, Gainesville, FL; 3Texas Children’s Cancer Center, Baylor College of Medicine, Houston, TX; 4University of Texas Southwestern Medical Center, Dallas, TX; 5University Miami School of Medicine, Miami, FL; 6Midwest Children’s Cancer Center, Milwaukee, WI; and 7University of Mississippi Medical Center Children’s Hospital, Jackson, MS, USA A prospective, randomized multicenter study was performed to to their risk for relapse and treatment strategies designed to evaluate the relative efficacy of two different concepts for early improve event-free survival (EFS). intensive therapy in a randomized trial of children with B-pre- cursor acute lymphoblastic leukemia (ALL) at high risk (HR) for It is believed that the leading causes of relapse in children relapse. Four hundred and ninety eligible children with HR-ALL with higher risk ALL (HR-ALL) are inadequate cell kill and were randomized on the Pediatric Oncology Group (POG) 9006 emergence of drug-resistant clones. Clinical trials using early phase III trial between 7 January 1991 and 12 January 1994. intensive myelosuppressive combination chemotherapy as After prednisone (PDN), vincristine (VCR), asparaginase (ASP) post-induction consolidation were designed to maximize cell and daunorubicin (DNR) induction, 470 patients received either 2 kill and address drug resistance.
    [Show full text]
  • Proper Use of Radiation Dose Metric Tracking for Patients Undergoing Medical Imaging Exams
    Proper Use of Radiation Dose Metric Tracking for Patients Undergoing Medical Imaging Exams Frequently Asked Questions Introduction In August of 2021, the American Association of Physicists in Medicine (AAPM), the American College of Radiology (ACR), and the Health Physics Society (HPS) jointly released the following position statement advising against using information about a patient’s previous cumulative dose information from medical imaging exams to decide the appropriateness of future imaging exams. This statement was also endorsed by the Radiological Society of North America (RSNA). It is the position of the American Association of Physicists in Medicine (AAPM), the American College of Radiology (ACR), and the Health Physics Society (HPS) that the decision to perform a medical imaging exam should be based on clinical grounds, including the information available from prior imaging results, and not on the dose from prior imaging-related radiation exposures. AAPM has long advised, as recommended by the International Commission on Radiological Protection (ICRP), that justification of potential patient benefit and subsequent optimization of medical imaging exposures are the most appropriate actions to take to protect patients from unnecessary medical exposures. This is consistent with the foundational principles of radiation protection in medicine, namely that patient radiation dose limits are inappropriate for medical imaging exposures. Therefore, the AAPM recommends against using dose values, including effective dose, from a patient’s prior imaging exams for the purposes of medical decision making. Using quantities such as cumulative effective dose may, unintentionally or by institutional or regulatory policy, negatively impact medical decisions and patient care. This position statement applies to the use of metrics to longitudinally track a patient’s dose from medical radiation exposures and infer potential stochastic risk from them.
    [Show full text]
  • THE STRUCTURED STORAGE of ONCOLOGICAL CHEMOTERAPEUTIC REGIMENS Contribution to Standardization of Therapeutic Procedures in Current Oncology
    THE STRUCTURED STORAGE OF ONCOLOGICAL CHEMOTERAPEUTIC REGIMENS Contribution to Standardization of Therapeutic Procedures in Current Oncology D. Klimes1, L. Dusek1, M. Kubasek1, J. Novotny2, J. Finek3 and R. Vyzula4 1 Institute of Biostatistics and Analyzes, Masaryk University, Kamenice 126/3, Brno, Czech Republik 2 Department of Oncology, General Teaching Hospital, Prague, Czech Republic 3 Charles University Prague, Medical Faculty Pilsen, Pilsen, Czech Republic 4 Masaryk Memorial Cancer Institute, Brno, Czech Republic Keywords: Cancer Chemotherapy Protocols, Antineoplastic Combined Chemotherapy Regimens, XML, Clinical Database. Abstract: The aim of the chemotherapeutic regimens (CHR) digitalization project is the proposal of a universal structure and creation of a publicly accessible database of contemporary CHR as a universal utility for the communication and evaluation of contemporary and newly defined clinical schedules in anti-tumor chemotherapy. After analysis of contemporary anti tumor CHR a standard XML structure was proposed, which enables the recording of simple CHR from the field of chemotherapy in solid adult tumors, and also has the potential of recording the complex treatment protocols in the field of paediatric oncology. The resulting XML documents were saved on a web server. A publicly accessible CHR database was constructed. There were a total of 130 XML documents with definitions of individual CHR in the first phase. Linked to this data store, three examples of web applications were added to demonstrate the potential uses of this newly created database. 1 INTRODUCTION clinical studies and are published in the oncological journals (Goldberg et al., 2004) (Henderson et al., Chemotherapy, along with surgery and radiotherapy 2003) (Citron et al., 2003) and subsequently in is an irreplaceable part of the clinical treatment of national or international guidelines (NCCN, 2006) oncological illnesses across nearly all diagnoses.
    [Show full text]
  • Incidence of Differentiation Syndrome Associated with Treatment
    Journal of Clinical Medicine Review Incidence of Differentiation Syndrome Associated with Treatment Regimens in Acute Myeloid Leukemia: A Systematic Review of the Literature Lucia Gasparovic 1, Stefan Weiler 1,2, Lukas Higi 1 and Andrea M. Burden 1,* 1 Institute of Pharmaceutical Sciences, Department of Chemistry and Applied Biosciences, ETH Zurich, 8093 Zurich, Switzerland; [email protected] (L.G.); [email protected] (S.W.); [email protected] (L.H.) 2 National Poisons Information Centre, Tox Info Suisse, Associated Institute of the University of Zurich, 8032 Zurich, Switzerland * Correspondence: [email protected]; Tel.: +41-76-685-22-56 Received: 30 August 2020; Accepted: 14 October 2020; Published: 18 October 2020 Abstract: Differentiation syndrome (DS) is a potentially fatal adverse drug reaction caused by the so-called differentiating agents such as all-trans retinoic acid (ATRA) and arsenic trioxide (ATO), used for remission induction in the treatment of the M3 subtype of acute myeloid leukemia (AML), acute promyelocytic leukemia (APL). However, recent DS reports in trials of isocitrate dehydrogenase (IDH)-inhibitor drugs in patients with IDH-mutated AML have raised concerns. Given the limited knowledge of the incidence of DS with differentiating agents, we conducted a systematic literature review of clinical trials with reports of DS to provide a comprehensive overview of the medications associated with DS. In particular, we focused on the incidence of DS reported among the IDH-inhibitors, compared to existing ATRA and ATO therapies. We identified 44 published articles, encompassing 39 clinical trials, including 6949 patients. Overall, the cumulative incidence of DS across all treatment regimens was 17.7%.
    [Show full text]
  • Arsenic Trioxide Is Highly Cytotoxic to Small Cell Lung Carcinoma Cells
    160 Arsenic trioxide is highly cytotoxic to small cell lung carcinoma cells 1 1 Helen M. Pettersson, Alexander Pietras, effect of As2O3 on SCLC growth, as suggested by an Matilda Munksgaard Persson,1 Jenny Karlsson,1 increase in neuroendocrine markers in cultured cells. [Mol Leif Johansson,2 Maria C. Shoshan,3 Cancer Ther 2009;8(1):160–70] and Sven Pa˚hlman1 1Center for Molecular Pathology, CREATE Health and 2Division of Introduction Pathology, Department of Laboratory Medicine, Lund University, 3 Lung cancer is the most frequent cause of cancer deaths University Hospital MAS, Malmo¨, Sweden; and Department of f Oncology-Pathology, Cancer Center Karolinska, Karolinska worldwide and results in 1 million deaths each year (1). Institute and Hospital, Stockholm, Sweden Despite novel treatment strategies, the 5-year survival rate of lung cancer patients is only f15%. Small cell lung carcinoma (SCLC) accounts for 15% to 20% of all lung Abstract cancers diagnosed and is a very aggressive malignancy Small cell lung carcinoma (SCLC) is an extremely with early metastatic spread (2). Despite an initially high aggressive form of cancer and current treatment protocols rate of response to chemotherapy, which currently com- are insufficient. SCLC have neuroendocrine characteristics bines a platinum-based drug with another cytotoxic drug and show phenotypical similarities to the childhood tumor (3, 4), relapses occur in the absolute majority of SCLC neuroblastoma. As multidrug-resistant neuroblastoma patients. At relapse, the efficacy of further chemotherapy is cells are highly sensitive to arsenic trioxide (As2O3) poor and the need for alternative treatments is obvious. in vitro and in vivo, we here studied the cytotoxic effects Arsenic-containing compounds have been used in tradi- of As2O3 on SCLC cells.
    [Show full text]
  • Daunorubicin Hydrochloride Injection Hikma Pharmaceuticals USA Inc
    DAUNORUBICIN HYDROCHLORIDE- daunorubicin hydrochloride injection Hikma Pharmaceuticals USA Inc. ---------- DAUNORUBICIN HYDROCHLORIDE INJECTION Rx ONLY WARNINGS 1.Daunorubicin Hydrochloride Injection must be given into a rapidly flowing intravenous infusion. It must never be given by the intramuscular or subcutaneous route. Severe local tissue necrosis will occur if there is extravasation during administration. 2.Myocardial toxicity manifested in its most severe form by potentially fatal congestive heart failure may occur either during therapy or months to years after termination of therapy. The incidence of myocardial toxicity increases after a total cumulative dose exceeding 400 to 550 mg/m2 in adults, 300 mg/m2 in children more than 2 years of age, or 10 mg/kg in children less than 2 years of age. 3.Severe myelosuppression occurs when used in therapeutic doses; this may lead to infection or hemorrhage. 4.It is recommended that daunorubicin hydrochloride be administered only by physicians who are experienced in leukemia chemotherapy and in facilities with laboratory and supportive resources adequate to monitor drug tolerance and protect and maintain a patient compromised by drug toxicity. The physician and institution must be capable of responding rapidly and completely to severe hemorrhagic conditions and/or overwhelming infection. 5.Dosage should be reduced in patients with impaired hepatic or renal function. DESCRIPTION Daunorubicin hydrochloride is the hydrochloride salt of an anthracycline cytotoxic antibiotic produced by a strain of Streptomyces coeruleorubidus. It is provided as a deep red sterile liquid in vials for intravenous administration only. Each mL contains 5 mg daunorubicin (equivalent to 5.34 mg of daunorubicin hydrochloride), 9 mg sodium chloride; sodium hydroxide and/or hydrochloric acid (to adjust pH), and water for injection, q.s.
    [Show full text]
  • 5-Fluorouracil + Adriamycin + Cyclophosphamide) Combination in Differentiated H9c2 Cells
    Article Doxorubicin Is Key for the Cardiotoxicity of FAC (5-Fluorouracil + Adriamycin + Cyclophosphamide) Combination in Differentiated H9c2 Cells Maria Pereira-Oliveira, Ana Reis-Mendes, Félix Carvalho, Fernando Remião, Maria de Lourdes Bastos and Vera Marisa Costa * UCIBIO, REQUIMTE, Laboratory of Toxicology, Faculty of Pharmacy, University of Porto, Rua de Jorge Viterbo Ferreira, 228, 4050-313 Porto, Portugal; [email protected] (M.P.-O.); [email protected] (A.R.-M.); [email protected] (F.C.); [email protected] (F.R.); [email protected] (M.L.B.) * Correspondence: [email protected] Received: 4 October 2018; Accepted: 3 January 2019; Published: 10 January 2019 Abstract: Currently, a common therapeutic approach in cancer treatment encompasses a drug combination to attain an overall better efficacy. Unfortunately, it leads to a higher incidence of severe side effects, namely cardiotoxicity. This work aimed to assess the cytotoxicity of doxorubicin (DOX, also known as Adriamycin), 5-fluorouracil (5-FU), cyclophosphamide (CYA), and their combination (5-Fluorouracil + Adriamycin + Cyclophosphamide, FAC) in H9c2 cardiac cells, for a better understanding of the contribution of each drug to FAC-induced cardiotoxicity. Differentiated H9c2 cells were exposed to pharmacological relevant concentrations of DOX (0.13–5 μM), 5-FU (0.13–5 μM), CYA (0.13–5 μM) for 24 or 48 h. Cells were also exposed to FAC mixtures (0.2, 1 or 5 μM of each drug and 50 μM 5-FU + 1 μM DOX + 50 μM CYA). DOX was the most cytotoxic drug, followed by 5-FU and lastly CYA in both cytotoxicity assays (reduction of 3-(4,5-dimethylthiazol-2- yl)-2,5-diphenyl tetrazolium bromide (MTT) and neutral red (NR) uptake).
    [Show full text]