ASH News Daily - Saturday, December 10, 2011 - (Page B-14)

Page B–14 ® ASH NewS DAily electronic presence.” He also plans to further develop the acquisition and production processes, as well as experiment with the format in which papers appear in the journal. “Blood should furnish the prime podium for reporting studies on clinical effectiveness in hematology.” As Editor-in-Chief, Dr. Löwenberg intends to “focus on the priorities that will enhance the role of Blood as the place to publish the best in hematology and narrow the gap between the journal and our (international) readers.” Dr. Löwenberg’s term begins in January 2013. Current Editor Cynthia Dunbar, MD, continues her term for one more year. Saturday, December 10, 2011 Blood «« From Page B-1 journal and/or abstracts into Spanish or Chinese. He feels that the success of globalization requires a greater level of active involvement from international associate editors and is up to the task of fostering an environment that will attract this community. Dr. Löwenberg is eager to explore new technology in order to enable Blood to reach the global masses. “We will continually need to adapt to the electronic developments that allow easy and flexible access to journals,” he remarks. “In five to 10 years I see Blood as a journal that has a strong Clinicians: Look for the Stethoscope Icon Identifying Clinically Relevant Abstracts S ince 2008, ASH has been identifying clinically relevant abstracts by marking them with a stethoscope icon in both the program and abstract books and in the online program. Selection of the clinically relevant abstracts is part of the blinded abstract peerreview process, which involves more than 400 reviewers. Coordinating reviewers in more than 50 scientific categories oversee groups of five reviewers who score and evaluate each abstract in their respective categories. Based on criteria developed by the ASH Committee on Practice, the reviewers recommend abstracts that are of particular interest to clinicians and pertinent to their daily practice. More than 500 have been identified this year. T:7” (AUC) ≥0.2% of the human exposure at the recommended dose of 14 mg/m2/week. Drug-related fetal effects consisted of folded retina, rotated limbs, and incomplete sternal ossification. 8.3 Nursing Mothers It is not known whether romidepsin is excreted in human milk. Because many drugs are excreted in human milk and because of the potential for serious adverse reactions in nursing infants from ISTODAX, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. 8.4 Pediatric Use The safety and effectiveness of ISTODAX in pediatric patients has not been established. 8.5 Geriatric Use Of the approximately 300 patients with CTCL or PTCL in trials, about 25% were > 65 years old. No overall differences in safety or effectiveness were observed between these subjects and younger subjects; however, greater sensitivity of some older individuals cannot be ruled out. 8.6 Hepatic Impairment No dedicated hepatic impairment study for ISTODAX has been conducted. Mild hepatic impairment does not alter pharmacokinetics of romidepsin based on a population pharmacokinetic analysis. Patients with moderate and severe hepatic impairment should be treated with caution [See Clinical Pharmacology (12.3)]. 8.7 Renal Impairment No dedicated renal impairment study for ISTODAX has been conducted. Based upon the population pharmacokinetic analysis, renal impairment is not expected to significantly influence drug exposure. The effect of end-stage renal disease on romidepsin pharmacokinetics has not been studied. Thus, patients with end-stage renal disease should be treated with caution [See Clinical Pharmacology (12.3)]. 10 OVERDOSAGE No specific information is available on the treatment of overdosage of ISTODAX. Toxicities in a single-dose study in rats or dogs, at intravenous romidepsin doses up to 2.2 fold the recommended human dose based on the body surface area, included irregular respiration, irregular heart beat, staggering gait, tremor, and tonic convulsions. In the event of an overdose, it is reasonable to employ the usual supportive measures, e.g., clinical monitoring and supportive therapy, if required. There is no known antidote for ISTODAX and it is not known if ISTODAX is dialyzable. 13 NONCLINICAL TOXICOLOGY 13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenicity studies have not been performed with romidepsin. Romidepsin was not mutagenic in vitro in the bacterial reverse mutation assay (Ames test) or the mouse lymphoma assay. Romidepsin was not clastogenic in an in vivo rat bone marrow micronucleus assay when tested to the maximum tolerated dose (MTD) of 1 mg/kg in males and 3 mg/kg in females (6 and 18 mg/m2 in males and females, respectively). These doses were up to 1.3-fold the recommended human dose, based on body surface area. Based on non-clinical findings, male and female fertility may be compromised by treatment with ISTODAX. In a 26-week toxicology study, romidepsin administration resulted in testicular degeneration in rats at 0.33 mg/kg/dose (2 mg/m2/dose) following the clinical dosing schedule. This dose resulted in AUC0-inf. values that were approximately 2% the exposure level in patients receiving the recommended dose of 14 mg/m2/dose. A similar effect was seen in mice after 4 weeks of drug administration at higher doses. Seminal vesicle and prostate organ weights were decreased in a separate study in rats after 4 weeks of daily drug administration at 0.1 mg/kg/day (0.6 mg/m2/day), approximately 30% the estimated human daily dose based on body surface area. Romidepsin showed high affinity for binding to estrogen receptors in pharmacology studies. In a 26-week toxicology study in rats, atrophy was seen in the ovary, uterus, vagina and mammary gland of females administered doses as low as 0.1 mg/kg/dose (0.6 mg/m2/dose) following the clinical dosing schedule. This dose resulted in AUC0-inf. values that were 0.3% of those in patients receiving the recommended dose of 14 mg/m2/dose. Maturation arrest of ovarian follicles and decreased weight of ovaries were observed in a separate study in rats after four weeks of daily drug administration at 0.1 mg/kg/day (0.6 mg/m2/day). This dose is approximately 30% the estimated human daily dose based on body surface area. 16 HOW SUPPLIED/STORAGE AND HANDLING Keep out of reach of children. Procedures for proper handling and disposal of anticancer drugs should be considered. Several guidelines on this subject have been published1-4 [See References (15)]. 17 PATIENT COUNSELING INFORMATION See FDA-approved patient labeling. 17.1 Instructions • Nausea and Vomiting Nausea and vomiting are common following treatment with ISTODAX. Prophylactic antiemetics are recommended to be used in all patients. Advise patients to report these symptoms so that appropriate treatment can be instituted [See Adverse Reactions (6)]. • Low Blood Counts Patients should be informed that treatment with ISTODAX can cause low blood counts and that frequent monitoring of hematologic parameters is required. Patients should be instructed to report fever or other signs of infection, significant fatigue, shortness of breath, or bleeding [See Warnings and Precautions (5.1)]. • Infections Patients should be informed that infections may occur during treatment with ISTODAX. Patients should be instructed to report fever, cough, shortness of breath with or without chest pain, burning on urination, flu-like symptoms, muscle aches, or worsening skin problems [See Warnings and Precautions (5.2)]. • Tumor Lysis Syndrome Patients at risk of tumor lysis syndrome (i.e, those with advanced stage disease and/or high tumor burden) should be monitored closely for TLS and appropriate measures taken if symptoms are observed [See Warnings and Precautions (5.4)]. • Use in Pregnancy If pregnancy occurs during treatment with ISTODAX, female patients should be advised to seek immediate medical advice and counseling. [See Warnings and Precautions (5.5)]. • Patients should be instructed to read the patient insert carefully. T:9.875” Manufactured for: Celgene Corporation Summit, NJ 07901 Manufactured by: Ben Venue Laboratories, Inc. Bedford, OH 44146 ISTODAX® is a registered trademark of Celgene Corporation U.S. Patents: 4,977,138; 7,608,280; 7,611,724 ISTBVPI.003/PPI.003 09/11 Cosmos Communications 718.482.1800 K 1 js Q1 Q2 

Table of Contents for the Digital Edition of ASH News Daily - Saturday, December 10, 2011

ASH News Daily - Saturday, December 10, 2011

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