DOCSLIB.ORG

Summary of Product Characteristics 1. Name Of

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Summary of Product Characteristics 1. Name Of SUMMARY OF PRODUCT CHARACTERISTICS 1. NAME OF THE MEDICINAL PRODUCT [XXX] 200 mg powder for solution for infusion [XXX] 1 g powder for solution for infusion 2. QUALITATIVE AND QUANTITATIVE COMPOSITION [For 200 mg strength:] Each vial contains 200 mg gemcitabine (as hydrochloride). Excipient: Each vial contains 3.5 mg sodium. [For 1 g strength:] Each vial contains 1 g gemcitabine (as hydrochloride). Excipient: Each vial contains 17.5 mg sodium. One ml of the reconstituted solution for infusion contains 38 mg gemcitabine (as hydrochloride). For a full list of excipients, see section 6.1. 3. PHARMACEUTICAL FORM Powder for solution for infusion. White to off-white lyophilized cake. The pH of the reconstituted solution is between pH 2.7 - 3.3. 4. CLINICAL PARTICULARS 4.1 Therapeutic indications. Bladder cancer: Treatment of locally advanced or metastatic bladder cancer, in combination with cisplatin. Breast cancer: Treatment of locally advanced or metastatic breast cancer in combination with paclitaxel in patients experiencing a relapse after (neo)adjuvant chemotherapy. Prior chemotherapy should have included an anthracycline, unless clinically contra-indicated. Non-small cell lung cancer: Treatment of locally advanced or metastatic non-small cell lung cancer, in monotherapy or in combination with cisplatin. Pancreatic cancer: Treatment of locally advanced or metastatic adenocarcinoma of the pancreas in patients who are in good general condition and with sufficient bone marrow reserves. 4.2 Posology and method of administration Upon reconstitution a colourless solution is the product. Treatment of gemcitabine should be started by, or in consultation with, a physician with considerable experience of cytotoxic medicinal products treatment (see also section 6.6 “Guidelines for the safe handling”). Bladder cancer (combination therapy): Adults: The recommended gemcitabine dose is 1000 mg/m2, given as a 30-minute infusion. The dose should be given on days 1, 8 and 15 of each 28-day treatment cycle in combination with cisplatin. Cisplatin is given at a recommended dose of 70 mg/m2 on day 2 of each 28-day treatment cycle. This 4-week cycle is subsequently repeated. Depending on the amount of toxicity observed in the patient, the dose can be reduced between treatment cycles or within an existing cycle. Breast cancer (combination therapy): Adults: The following dosing regimen is recommended for the gemcitabine + paclitaxel combination: Paclitaxel (175 mg/m2) is intravenously infused over 3 hours on day 1 followed by gemcitabine1250 mg/m2 intravenously infused for 30 minutes on days 1 and 8 of each 21-day treatment cycle. Depending on the amount of toxicity observed in the patient, the dose can be reduced between treatment cycles or within an existing cycle. Prior to use of the gemcitabine + paclitaxel combination, the patient should have an absolute granulocyte count of at least 1.5 x 109/l. Non-small cell lung cancer (combination therapy): Adults: For the gemcitabine + cisplatin combination, the application of two dosing regimens has been investigated; one regimen with a three-week treatment cycle and the other with a four-week cycle. During the three-week treatment cycle, the gemcitabine dose is 1250 mg/m2, given by 30-minute intravenous infusion, on days 1 and 8 of each 21-day cycle. Depending on the amount of toxicity observed in the patient, the dose can be reduced between treatment cycles or within an existing cycle. During the four-week treatment cycle, the gemcitabine dose is 1000 mg/m2, given by 30 minute intravenous infusion, on days 1, 8 and 15 of each 28-day cycle. Depending on the amount of toxicity observed in the patient, the dose can be reduced between treatment cycles or within an existing cycle. Cisplatin has been used at doses between 75-100 mg/m2 once every 3 or 4 weeks. Non-small cell lung cancer (mono therapy): Adults: The recommended dose of gemcitabine is 1000 mg/m2, given by 30 minute intravenous infusion. This should be repeated once weekly for three weeks, followed by a one week rest period. This four-week cycle is then repeated. Dosage reduction is applied based upon the amount of toxicity experienced by the patient. Pancreatic cancer: Adults: The recommended gemcitabine dose is 1000 mg/m2, given as a 30-minute infusion. This should be repeated once weekly for up to 7 weeks, followed by one week of rest. For subsequent treatment cycles, a once-weekly infusion should be given for a period of three consecutive weeks, followed by one week of rest. Depending on the amount of toxicity observed in the patient, the dose can be reduced between treatment cycles or within an existing cycle. Monitoring, adjustment or dose escalation and end of treatment: Prior to each dose, patients must be monitored for platelet, leukocyte, and granulocyte counts (see section 4.4). If necessary, at the onset of any haematological effects, the dose must be reduced or treatment temporarily suspended. Reductions in the gemcitabine dose on days 8 and/or 15 due to blood toxicity should take place in accordance with the guidelines given in Tables 1-2 below. Table 1: Adjustment of the gemcitabine dose on days 8 and/or 15 in cases of bladder cancer, non- small cell lung cancer and pancreatic cancer Absolute granulocyte count (x109/l) Platelet Dosage count (x 109/l) > 1 and > 100 100% of the normal dose 0.5 – 1 or 50 – 100 75% of the normal dose < 0.5 or < 50 Discontinuation of treatment* Table 2: Adjustment of the gemcitabine dose on day 8 in patients with breast cancer Absolute granulocyte count (x109/l) Platelet Dosage count (x 109/l) ≥1.2 and > 75 100% of the normal dose 1 - < 1.2 or 50 – 75 75% of the normal dose 0.7 - <1 and ≥ 50 50% of the normal dose < 0.7 or < 50 Discontinuation of treatment* * Treatment can be continued on day 1 of the next treatment cycle. At the onset of the following haematological toxic effects, the dose for subsequent treatment cycles should be gradually titrated by one dose level (see Table 3). • absolute neutrophil count <0.5 x 109/l for more than 5 days • absolute neutrophil count <0.1 x 109/l for more than 3 days • febrile neutropenia, i.e. temperature ≥38°C, absolute neutrophil count <1.0 x 109/l, necessitating hospitalisation and use of an intravenous antibiotic. • platelets <25 x 109/l • > 1-week postponement of subsequent treatment cycle due to toxicity. Table 3: Dose levels for gemcitabine and carboplatin Dose level 0 - 1 - 2 1000 mg/m2 on days 800 mg/m2 on days 800 mg/m2 on day 1 Gemcitabine 1 and 8 1 and 8 Carboplatin AUC 4.0 on day 1 AUC 4.0 on day 1 AUC 4.0 on day 1 During treatment with gemcitabine, hepatic and renal function, as well as transaminase (AST/ALT) and serum creatinine levels, must be regularly monitored for non-haematological toxicity. Depending on individual tolerance, the dose can be reduced during the existing treatment cycle or the following cycle. The reduced dose should be given until toxicity begins to recede. Elderly patients: Gemcitabine has been well tolerated in patients over the age of 65. There is no evidence to suggest that dose adjustments are necessary in the elderly, although Gemcitabine clearance and half-life are affected by age. Children: Safety and efficacy of gemcitabine in children has not been established, therefore its use is not recommended. Patients with impaired hepatic or renal function: Gemcitabine should be used with caution in patients with hepatic or renal impairment. Studies have been performed in patients with moderate hepatic or renal impairment, dose adjustment was not needed. There are no data available in case of severe impairment (see sections, 4.4 and 4.8). Administration: Gemcitabine should be reconstituted and diluted afterwards before use (see section 6.6). Gemcitabine is well tolerated during the infusion, with only a few cases of injection site reaction reported and can be administered on an outpatient basis. 4.3 Contraindications • Hypersensitivity to the active substance (gemcitabine) or to any of the excipients. • Use during breast-feeding. • Concomitant administration of yellow fever vaccine (see sections 4.5 and 4.8). 4.4 Special warnings and precautions for use General: Treatment with gemcitabine should be started by, or in consultation with, a physician with considerable experience in the use of cytotoxic medicinal products. Patients receiving therapy with Gemcitabine must be monitored closely. Laboratory facilities should be available to monitor patient status. Treatment for a patient compromised by drug toxicity may be required. Prolongation of the infusion time and increased dosing frequency have been shown to increase toxicity. Live attenuated vaccines and phenytoin This product is generally not recommended in combination with live attenuated vaccines and phenytoin. Radiation therapy: See section 4.5. Patients with hepatic and renal impairment: Gemcitabine may not be given to patients with moderate-to-severe hepatic impairment or severe renal impairment (see sections 4.2 and 4.8). Gemcitabine must be used with caution in patients with mild hepatic impairment and those with mild-to-moderate renal dysfunction, as there is insufficient information from clinical studies to allow any clear dosage recommendations for these patient groups. Administration of gemcitabine to patients with a history of liver metastases or hepatitis, alcoholism or liver cirrhosis may lead to exacerbation of the underlying hepatic dysfunction. Based on the few data available, no constant significant effects on the pharmacokinetic properties of gemcitabine were observed in patients with mild-to-moderate renal dysfunction (glomerular filtration rate: 30-80 ml/min). A few cases of renal failure, including haemolytic-uraemic syndrome, have been reported. In patients with impaired renal function, gemcitabine should only be administered with caution (see section 4.8).
Load more

Recommended publications
  • Modifications of Nucleic Acid Precursors That Inhibit Plant Virus Multiplication
    Molecular Plant Pathology Modifications of Nucleic Acid Precursors That Inhibit Plant Virus Multiplication William 0. Dawson and Carol Boyd Department of Plant Pathology, University of California, Riverside 92521. This work was supported in part by U.S. Department of Agriculture Grant 84-CTC-1-1402. Accepted for publication 4 April 1986. ABSTRACT Dawson, W. 0., and Boyd, C. 1987. Modifications of nucleic acid precursors that inhibit plant virus multiplication. Phytopathology 77:477-480. The relationship between chemical modifications of normal nucleic acid highest proportion of antiviral activity were modification of the sugar base or nucleoside precursors and ability to inhibit multiplication of moiety (five of 13 chemicals were inhibitory) and addition of abnormal side tobacco mosaic virus or cowpea chlorotic mottle virus in disks from groups (three of seven chemicals were inhibitory). Eight new inhibitors of mechanically inoculated leaves was tested with 131 analogues. Chemicals virus multiplication were identified: 6-aminocytosine; 6-ethyl- tested were selected from 10 general classes of modifications to determine mercaptopurine; isopentenyladenosine; 2-thiopyrimidine; 2,4-dithio- the types of modifications of normal nucleic acid precursors that have pyrimidine; melamine; 5'-iodo-5'-deoxyadenosine; and 5'- greater probabilities of inhibiting virus multiplication. No inhibitory methyl-5'-deoxythioadenosine. chemicals were found in several classes. Classes of modifications with the Additionalkey words: antivirals, chemotherapy, control, virus diseases. The ability to control virus diseases of plants with chemicals different taxonomic groups, tobacco mosaic virus (TMV) in would be a valuable addition to existing control strategies. This tobacco and cowpea chlorotic mottle virus (CCMV) in cowpea. could be particularly useful in in vitro culture procedures to Chemicals were chosen to be tested based on two different criteria.
    [Show full text]
  • R&D Briefing 76
    The Impact of Recent Regulatory Developments on the Mexican Therapeutic Landscape Access to innovative medicines is key to El acceso a medicamentos innovadores es clave para improving overall population health, reducing mejorar la salud de toda la población, para reducir los hospitalisation time and decreasing morbidity and tiempos de hospitalización, la morbilidad y la mortalidad mortality. An efficient regulatory process can be de un país. Un proceso regulatorio eficiente tiene un reflected in measurable positive health impacts; impacto positivo medible en la salud, y por el contrario, conversely, activities that slow or impede acciones que retrasan o impiden la eficiencia regulatoria y regulatory efficiency and predictability can be su predictibilidad pueden ser perjudiciales. La parálisis detrimental. Recent developments in the Mexican reciente del Sistema regulatorio mexicano respecto a la regulatory system for the assessments of evaluación de nuevos medicamentos innovadores innovative new products have had a negative conlleva un impacto negativo en la salud de la población impact on Mexican public health. mexicana. This Briefing addresses the impact of suspending Este informe analiza el impacto de la suspensión de las the activities of the New Molecules Committee actividades del Comité de Moléculas Nuevas (NMC, por (NMC) on the Mexican therapeutic landscape. sus siglas en inglés) sobre el horizonte terapéutico de First, we compared the way that “new medicines” México. En primer lugar, comparamos la definición de are defined within the context of the Mexican nuevos medicamentos según el contexto regulatorio regulatory system, with definitions used by mexicano con las definiciones adoptadas por otras comparable regulators and health organisations. agencias reguladoras u organizaciones de salud del We have also investigated the extent to which mundo.
    [Show full text]
  • Cancer Drug Pharmacology Table
    CANCER DRUG PHARMACOLOGY TABLE Cytotoxic Chemotherapy Drugs are classified according to the BC Cancer Drug Manual Monographs, unless otherwise specified (see asterisks). Subclassifications are in brackets where applicable. Alkylating Agents have reactive groups (usually alkyl) that attach to Antimetabolites are structural analogues of naturally occurring molecules DNA or RNA, leading to interruption in synthesis of DNA, RNA, or required for DNA and RNA synthesis. When substituted for the natural body proteins. substances, they disrupt DNA and RNA synthesis. bendamustine (nitrogen mustard) azacitidine (pyrimidine analogue) busulfan (alkyl sulfonate) capecitabine (pyrimidine analogue) carboplatin (platinum) cladribine (adenosine analogue) carmustine (nitrosurea) cytarabine (pyrimidine analogue) chlorambucil (nitrogen mustard) fludarabine (purine analogue) cisplatin (platinum) fluorouracil (pyrimidine analogue) cyclophosphamide (nitrogen mustard) gemcitabine (pyrimidine analogue) dacarbazine (triazine) mercaptopurine (purine analogue) estramustine (nitrogen mustard with 17-beta-estradiol) methotrexate (folate analogue) hydroxyurea pralatrexate (folate analogue) ifosfamide (nitrogen mustard) pemetrexed (folate analogue) lomustine (nitrosurea) pentostatin (purine analogue) mechlorethamine (nitrogen mustard) raltitrexed (folate analogue) melphalan (nitrogen mustard) thioguanine (purine analogue) oxaliplatin (platinum) trifluridine-tipiracil (pyrimidine analogue/thymidine phosphorylase procarbazine (triazine) inhibitor)
    [Show full text]
  • Renal Clinical Pharmacy Services“
    DISSERTATION „Renal clinical pharmacy services“ Mag.pharm. Gunar Stemer angestrebter akademischer Grad Doktor der Naturwissenschaften (Dr.rer.nat.) Wien, 2011 Studienkennzahl lt. Studienblatt: A 091 449 Dissertationsgebiet lt. Studien- Pharmazie blatt: Betreuerin / Betreuer: Ao. Univ. Prof. Mag. Dr. Rosa Lemmens 2 e pensando di lei mi sopragiunse uno soave sonno ego dominus tuus vide cor tuum e d’esto core ardendo cor tuum lei paventosa umilmente pascea appreso gir io ne vedea piangendo la letizia si convertia in amarissimo pianto io sono in pace cor meum io sono in pace vide cor meum Dante Alighieri La Vita Nuova ~1293 Gewidmet meinen Eltern Annelies und Franz, in aufrichtiger Dankbarkeit und Liebe Dedicated to my parents Annelies and Franz, in sincere gratitude and love 3 4 ACKNOWLEDGEMENTS This thesis would not have been possible without the continuous support, help, and contributions of so many colleagues, companions, friends, and beloved family members. First, I want to express my deepest gratitude to my doctoral advisor, Mrs. Prof. Rosa Lemmens, for her commitment in supervising my thesis work, her support during the writing of this thesis, several constructive discussions with her, and her critical comments. My sincerest thanks are extended to the head of the pharmacy department of the Vienna General Hospital, Mrs. SR Mag. Elfriede Dolinar, for providing me with this unique opportunity to work on the topic of clinical pharmacy and, thus, contribute to the evolution of the complete hospital pharmacy and clinical pharmacy discipline in Austria. I would like to thank her for her trust in my capabilities to succeed in this demanding project over the last three years by implementing new services, her vision regarding the discipline of hospital pharmacy, her overall contribution to the development of the profession of hospital pharmacy, and her continuous belief in the value of clinical pharmacy services.
    [Show full text]
  • Structural Basis for the Inhibition of Human 5,10-Methenyltetrahydrofolate Synthetase by N10-Substituted Folate Analogues
    Published OnlineFirst September 8, 2009; DOI: 10.1158/0008-5472.CAN-09-1927 Experimental Therapeutics, Molecular Targets, and Chemical Biology Structural Basis for the Inhibition of Human 5,10-Methenyltetrahydrofolate Synthetase by N10-Substituted Folate Analogues Dong Wu,1 Yang Li,1 Gaojie Song,1 Chongyun Cheng,1 Rongguang Zhang,2 Andrzej Joachimiak,2 NeilShaw, 1 and Zhi-Jie Liu1 1National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China and 2Structural Biology Center, Argonne National Laboratory, Argonne, Illinois Abstract of the one-carbon metabolic network, dihydrofolate reductase, 5,10-Methenyltetrahydrofolate synthetase (MTHFS) regulates which catalyzes the conversion of dihydrofolate to tetrahydrofolate. the flow of carbon through the one-carbon metabolic network, Similarly, colorectal and pancreatic cancers are routinely treated by which supplies essential components for the growth and administration of the pyrimidine analogue 5-fluorouracil (5-FU), proliferation of cells. Inhibition of MTHFS in human MCF-7 which inhibits thymidylate synthase (TS; ref. 6). TS converts breast cancer cells has been shown to arrest the growth of deoxyuridylate to deoxythymidylate using a carbon donated by cells. Absence of the three-dimensional structure of human 5,10-methylenetetrahydrofolate (Fig. 1). This conversion is essential MTHFS (hMTHFS) has hampered the rational design and for DNA synthesis (7). To increase the clinical efficiency of the optimization of drug candidates. Here, we report the treatment, 5-formyltetrahydrofolate is often coadministered along structures of native hMTHFS, a binary complex of hMTHFS with 5-FU. The beneficial effect of administering 5-formyltetrahy- with ADP, hMTHFS bound with the N5-iminium phosphate drofolate during the therapy with 5-FU is a consequence of the reaction intermediate, and an enzyme-product complex of 5,10-methenyltetrahydrofolate synthetase (MTHFS)–catalyzed hMTHFS.
    [Show full text]
  • Bendamustine and Cytosine Arabinoside: a Highly Synergistic Combination Visco C*, Carli G and Rodeghiero F Further DNA Synthesis [24]
    Open Access Austin Journal of Cancer and Clinical Research Editorial Bendamustine and Cytosine Arabinoside: A Highly Synergistic Combination Visco C*, Carli G and Rodeghiero F further DNA synthesis [24]. The synergistic effect of bendamustine Department of Cell Therapy and Hematology, San Bortolo and cytarabine could be related to the individual mechanism of Hospital, Italy action of the two drugs, whose serial administration would avoid *Corresponding author: Carlo Visco, Department of the saturation of the common pathways. Cells escaping the cell cycle Cell Therapy and Hematology, San Bortolo Hospital, Via arrest induced by bendamustine and trying to repair their damage Rodolfi 37, 36100 Vicenza, Italy, Tel: +39 0444 753626; would be prone to incorporate the metabolite ara-CTP into DNA, Fax: +39 0444 920708; Email: [email protected] as reported by Staib [19] in acute myeloid leukemia cells. Indeed, the Received: January 07, 2015; Accepted: March 16, sequential treatment with bendamustine followed by cytarabine was 2015; Published: April 03, 2015 proven to be more effective than simultaneous addition of the two drugs (Figure 2) [21-23]. The S phase of the cell cycle is a crucial step Editorial of replication in mantle cell lymphoma (MCL) cells, where cyclin D1 Bendamustine is a bifunctional compound that has shown clinical overexpression deregulates the cell cycle at the G1/S phase transition, activity against various human cancers including non-Hodgkin’s and and is likely the engine continuously pushing cells towards S-phase Hodgkin’s lymphoma [1,2], chronic lymphocytic leukemia (CLL) [3], (Figure 3). Indeed, both drugs are known to be particularly active in multiple myeloma [4,5], breast cancer [6], and small-cell lung cancer patients with MCL.
    [Show full text]
  • PD-1 / PD-L1 Combination Therapies
    PD-1 / PD-L1 Combination Therapies Jacob Plieth & Edwin Elmhirst – November 2015 Foreword Biopharma owes much of the past few years’ bull run to advances in cancer – specifically to immuno-oncology approaches that harness the natural power of the immune system to combat disease. The charge has been led by antibodies against CTLA4 and PD-1, which have seen the launches of Yervoy, Opdivo and Keytruda, initially for melanoma but with additional indications now getting under way. What does the industry do for an encore? There are several late-stage antibodies that work in identical or similar ways – tremelimumab, atezolizumab and durvalumab – and slightly further away stands an amazing array of novel immuno-oncology approaches, which target novel antigens or novel immune system checkpoints. But most experts are now looking to combinations to build on the success of the first few immuno-oncology drugs to hit the market. This is a vital theme because, in investment terms, biopharma looks like it might at last have overheated, and as such it is desperate for another lift. The coming 18 months could provide several. The key lies in the first clinical evidence from early trials of anti-PD-1 and anti-PD-L1 antibodies combined with novel immune system agents, as well as in combination with a barrage of old and new small-molecule and antibody drugs, chemotherapies, cancer vaccines and gene therapies. Combining numerous new and old approaches with anti-PD-1/PD-L1 agents is logical given that the latter already look like they are becoming standard treatment in certain populations within certain tumour types.
    [Show full text]
  • Drug Therapy of Cancer Curt Peterson
    Drug therapy of cancer Curt Peterson To cite this version: Curt Peterson. Drug therapy of cancer. European Journal of Clinical Pharmacology, Springer Verlag, 2011, 67 (5), pp.437-447. 10.1007/s00228-011-1011-x. hal-00671936 HAL Id: hal-00671936 https://hal.archives-ouvertes.fr/hal-00671936 Submitted on 20 Feb 2012 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. 1 110130 Drug therapy of cancer Curt Peterson Professor, MD, PhD Departments of Clinical Pharmacology and Oncology University hospital SE-581 85 Linköping Sweden [email protected], tel: +46101031090, fax: +4613104195 2 Abstract Cancer chemotherapy was introduced at the same time as antibacterial chemotherapy but has not at all been such a success. However, there is a growing optimism in oncology today due to the introduction of several more or less target specific drugs as complement to the conventional cytotoxic drugs introduced half a century ago. The success in the treatment of chronic myelogenous leukemia by imatinib, inhibiting the bcr-abl activated tyrosine kinase thereby interrupting the signal transduction pathways that lead to leukemic transformation. with impressive survival benefit has paved the way for this new optimism.
    [Show full text]
  • VOL. XXVII, No. 3-4, 2011 20112011 Heart Diseases in Essential Thrombocythemia Review
    VOL. XXVII, No. 3-4, 2011 20112011 Heart diseases in essential Thrombocythemia review Mihaela Rugină1 , L. Predescu 1, V.Molfea 1, I. M. Coman 1,2,Ş . Bubenek- Turconi 1,2 1. “C.C.Iliescu" Emergency Institute for Cardiovascular Diseases 2. “Carol Davila” University of Medicine and Pharmacy, Bucharestepartment of the Emergency Universitary Hospital –Bucharest Contact address: Dr. Mihaela Rugină,Ş , “C.C.Iliescu" Emergency Institute for Cardiovascular Diseases os. Fundeni 258, Sector 2, 022328, Bucharest • E-mail: [email protected] Abstract Essential thrombocythemia (ET) is a myeloproliferative disorder that raises questions about the characteristics of the disease treatment. ET evolution is grafted to a predisposition to bleeding and thrombotic events and microvascular events. Thrombotic events often affects medium-sized and large arteries including cerebral arteries, coronary and peripheral, but can also affect the veins causing recurrent venous thrombosis of the legs with thromboembolic complications. The most common cardiac complications occurred in the ET are the acute coronary syndromes or coronary thrombosis, and in some cases has been incriminated and coronary spasm. Possible cardiac valvular damage that can occur in ET (thickening, calcification, valvular regurgitation) and the possibility of associating with pulmonary arterial hypertension who aren't associated to a pulmonary embolism are reported in the literature but with an extremely rare incidence. Key words: essential thrombocythemia, acute coronary syndroms, thrombosis
    [Show full text]
  • Summary of Product Characteristics
    Health Products Regulatory Authority Summary of Product Characteristics 1 NAME OF THE MEDICINAL PRODUCT Etoposide ”Ebewe ” 20 mg/ml – Concentrate for solution for infusion 2 QUALITATIVE AND QUANTITATIVE COMPOSITION 1 ml of concentrate for solution for infusion contains 20 mg of etoposide. 1, 5, or 10 vials of 2.5 ml concentrate for solution for infusion contains 50 mg etoposide. 1, 5, or 10 vials of 5 ml concentrate for solution for infusion contains 100 mg etoposide. 1, 5, or 10 vials of 10 ml concentrate for solution for infusion contains 200 mg etoposide. 1, 5, or 10 vials of 20 ml concentrate for solution for infusion contains 400 mg etoposide. 1, 5, or 10 vials of 50 ml concentrate for solution for infusion contains 1000 mg etoposide. Excipients: Benzyl alcohol, ethanol. For a full list of excipients, see section 6.1. 3 PHARMACEUTICAL FORM Concentrate for solution for infusion. Clear, light yellow solution. 4 CLINICAL PARTICULARS 4.1 Therapeutic Indications Etoposide is a antineoplastic agent for intravenous use. It can be used alone or in combination with other oncolytic agents. Available data show that etoposide may be used in treatment of small -celled lung cancer, resistant non -seminomatous testicular carcinoma, acute myelomonocytic and myelocytic leukaemia (AML, FAB subtype M4 or M5) as part of combination therapy after failure of induction chemotherapy. 4.2 Posology and method of administration Etoposide should be administered only by or under the direct supervision of a qualified physician who is experienced in the use of cancer chemotherapeutic agents. Pregnant personnel should not handle chemotherapeutic agents.
    [Show full text]
  • Highly Halaven-Resistant KBV20C Cancer Cells Can Be Sensitized by Co-Treatment with Fluphenazine JI HYUN CHEON, BYUNG MU LEE, HYUNG SIK KIM and SUNGPIL YOON
    ANTICANCER RESEARCH 36 : 5867-5874 (2016) doi:10.21873/anticanres.11172 Highly Halaven-resistant KBV20C Cancer Cells Can Be Sensitized by Co-treatment with Fluphenazine JI HYUN CHEON, BYUNG MU LEE, HYUNG SIK KIM and SUNGPIL YOON School of Pharmacy, Sungkyunkwan University, Suwon, Republic of Korea Abstract. Aim: To identify conditions that induce an increase developed and used in the clinic to treat resistant or metastatic in the sensitivity of highly Halaven (HAL)-resistant cancer cells cancer. HAL has been developed to overcome the resistance compared to sensitive cells. Materials and Methods: We of cancer cells to routinely used antimitotic drugs. HAL observed that drug-resistant KBV20C cells are highly resistant targets the depolymerization of microtubules (5, 6). HAL is to HAL compared to other antimitotic drugs. The concentration considered a promising drug for triple-negative breast cancer required to treat KBV20C cells was almost 500-fold higher than or certain resistant cancers (7, 8). Since patients are expected that used to treat sensitive parent KB cells. In order to increase to develop resistance to HAL, identifying the mechanism(s) sensitization, HAL-treated KBV20C cells were co-treated with that underlie cell sensitization to HAL would be an important the repositioned drug, fluphenazine (FLU). Results: HAL and step in the development of more effective treatments by FLU co-treatment inhibited the growth and increased apoptosis designing approaches to increase HAL-associated apoptosis. via G 2 arrest in HAL-treated KBV20C cancer cells. In the present study, we determined that P-glycoprotein Sensitization by HAL-FLU affected retinoblastoma protein (P-gp)-overexpressing KBV20C cells are highly resistant to (pRB), pHistone H3 and pH2AX protein levels.
    [Show full text]
  • Dihydropyrimidine Dehydrogenase in the Metabolism of the Anticancer Drugs
    Cancer Chemotherapy and Pharmacology (2019) 84:1157–1166 https://doi.org/10.1007/s00280-019-03936-w REVIEW ARTICLE Dihydropyrimidine dehydrogenase in the metabolism of the anticancer drugs Vinay Sharma1 · Sonu Kumar Gupta1 · Malkhey Verma1 Received: 3 May 2019 / Accepted: 21 August 2019 / Published online: 4 September 2019 © Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract Cancer caused by fundamental defects in cell cycle regulation leads to uncontrolled growth of cells. In spite of the treatment with chemotherapeutic agents of varying nature, multiple resistance mechanisms are identifed in cancer cells. Similarly, numerous variations, which decrease the metabolism of chemotherapeutics agents and thereby increasing the toxicity of anticancer drugs have been identifed. 5-Fluorouracil (5-FU) is an anticancer drug widely used to treat many cancers in the human body. Its broad targeting range is based upon its capacity to act as a uracil analogue, thereby disrupting RNA and DNA synthesis. Dihydropyrimidine dehydrogenase (DPD) is an enzyme majorly involved in the metabolism of pyrimidines in the human body and has the same metabolising efect on 5-FU, a pyrimidine analogue. Multiple mutations in the DPD gene have been linked to 5-FU toxicity and inadequate dosages. DPD inhibitors have also been used to inhibit excessive degradation of 5-FU for meeting appropriate dosage requirements. This article focusses on the role of dihydropyrimidine dehydrogenase in the metabolism of the anticancer drug 5-FU and other associated drugs. Keywords Cancer · Anticancer drugs · Dihydropyrimidine dehydrogenase (DPD) · 5-Fluorouracil (5-FU) · Drug resistance · Drug metabolism Introduction by Dihydropyrimidine dehydrogenase (DPD) through the pyrimidine degradation pathway.
    [Show full text]