High-Risk Factor: Off-Label Use Of Clotting Drug

Science ◽  
2011 ◽  
Vol 332 (6028) ◽  
pp. 404-404
Keyword(s):  
Risk Factor ◽  
High Risk ◽  
Off Label Use ◽  
Off Label ◽  
High Risk Factor ◽  
Label Use

Safety of Clofarabine with Multiagent Chemotherapy in Childhood High Risk Relapse of Acute Lymphoblastic Leukemia (Vandevol study of the French SFCE Acute Leukemia Committee).

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2570-2570
Author(s):  
Brigitte Nelken ◽  
Guy Leverger ◽  
Claire Galambrun ◽  
Genevieve Plat ◽  
Claudine Schmitt ◽  
...  
Keyword(s):  
High Risk ◽  
Dose Level ◽  
Bacterial Infections ◽  
Lymphoblastic Leukemia ◽  
Single Agent ◽  
Off Label Use ◽  
Childhood All ◽  
Off Label ◽  
Post Transplant ◽  
Label Use

Abstract Abstract 2570 Background. Current outcome of very early relapse of ALL in children remains poor. Clofarabine, a novel nucleoside analog has proven effective as a single agent in childhood ALL second relapse, providing a CR+CRp ratio of 20 to 28 % (Jeha 2006, Kearns 2006). Clofarabine in combination with cyclophosphamide and Etoposide provided a 44% overal response rate rate in children with advanced ALL (Hijiya 2011) and further multi-drug combinations need to be investigated. The VANDA regimen that has proven effective in high risk ALL and in ALL relapse (Domenech 2008) was used as a template, Cytarabine being replaced by Clofarabine in this combination. Procedure. A phase I study combining escalating doses of Clofarabine with fixed doses of Mitoxantrone, Etoposide, Asparaginase and Dexamethasone was undertaken in children presenting very early (18 months or less after initial diagnosis) medullary or combined ALL relapse or children with second relapse or post transplant relapse. A 3+3 rolling design was used for escalating clofarabine doses with 25% increments from 20 to 40mg/m2/d. Results. Sixteen patients were enrolled, eleven in first marrow relapse, four in second relapse. One patient with an initially refractory disease was secondary excluded as he didn't fulfill the inclusion criteria. Four patients had previously been allografted. Three patients were enrolled at dose level 1 (clofarabine 20 mg/m2), and 3 patients at dose level 2 (clofarabine 26 mg/m2) without any significant dose-limiting toxicity (DLT). Six patients were enrolled at dose level 3 (clofarabine 32 mg/m2), one patient experienced a liver DLT (gamma GT elevation) exceeding 7 days. At the last planned dose level (clofarabine 40 mg/m2), two patients had a grade 3 transaminase elevation exceeding 7 days and 2 patients had a severe fungal infection. Median duration of neutropenia was 20 days (15–31). Other expected toxicities included 3 documented bacterial infections, 3 mucosal toxicities needing parenteral support, one lung aspergillosis, one transient insulin dependant hyperglycemia. There was no toxic death. Out of 15 evaluable patients, 11 (73%) achieved a complete cytological remission (CR). 4 relapses occurred at 1, 1, 2 and 3 months. 6 patients proceeded to allo-SCT with 2 second allografts. One allografted patient died from EBV-PTLD, the others are alive at 2, 13, 13, 15, and 29 months post-transplant. Conclusion. Clofarabine in combination with four major antileukemic drugs appeared feasible and effective in inducing complete remission in those high risk patients. Clofarabine MTD was 32 mg/m2/d for five days and this dose step is currently being expanded to a total of 10 patients, before a phase II study will be proposed for early and very early ALL relapses. Study registered at ClinicalTrials.gov (http://clinicaltrials.gov/ct2/show/NCT01279096). Disclosures: Off Label Use: off label use of clofarabine.

scholarly journals Patterns of Off-Label Prescribing in the Pediatric Intensive Care Unit and Prioritizing Future Research

2015 ◽  
Vol 20 (3) ◽  
pp. 186-196 ◽  
Author(s):  
Angela S. Czaja ◽  
Pamela D. Reiter ◽  
M. Lynn Schultz ◽  
Robert J. Valuck
Keyword(s):  
Intensive Care ◽  
High Risk ◽  
Pediatric Intensive Care ◽  
Future Research ◽  
Off Label Use ◽  
Off Label ◽  
Lengths Of Stay ◽  
Uncertain Evidence ◽  
Organ Failures ◽  
Label Use

OBJECTIVES: To characterize off-label prescribing among US pediatric intensive care units (PICUs), determine characteristics associated with off-label use, and identify medications in highest need for additional study. METHODS: Medications prescribed for ≥1% PICU patients (age < 18 years) in 2010 were identified from 39 children's hospitals. Use in a patient younger than the Food and Drug Administration (FDA)-approved age for any indication was considered off-label. Hierarchical multivariable modeling was used to identify characteristics associated with off-label use, accounting for center effects. Highest-impact drugs were defined by: 1) high off-label use (off-label use in at least 5% of the PICU cohort), 2) high risk medication, and 3) high priority status by the FDA or Best Pharmaceuticals for Children Act (BPCA). RESULTS: A total of 66,896 patients received ≥1 medication of interest (n = 162) during their PICU stay. A median of 3 (interquartile range, 2–6) unique drugs per patient were used off-label. Those who received ≥1 drug off-label (85% of the cohort) had longer median PICU (2 days vs 1 day) and hospital (6 days vs 3 days) lengths of stay and higher mortality (3.6% vs 0.7%), p < 0.001. Factors independently associated with off-label drug use included: age 1 to 5 years, chronic conditions, acute organ failures, mechanical ventilation, arterial or venous catheters, dialysis, and blood products. Half of prescribed medications (n = 84) had been used off-label: 26 with significant off-label use, 30 high-risk medications, and 47 with high FDA/BPCA priority. The highest impact medications identified were: dexmedetomidine, dopamine, hydromorphone, ketamine, lorazepam, methadone, milrinone, and oxycodone. CONCLUSIONS: Most PICU patients are exposed to off-label medication use, with uncertain evidence. Future medication research in this population should focus on medications with high impact potential.

Improved Outcome with ATRA-Arsenic Trioxide Compared to ATRA-Chemotherapy in Non-High Risk Acute Promyelocytic Leukemia – Updated Results of the Italian-German APL0406 Trial on the Extended Final Series

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 12-12 ◽  
Author(s):  
Uwe Platzbecker ◽  
Giuseppe Avvisati ◽  
Gerhard Ehninger ◽  
Laura Cicconi ◽  
Christian Thiede ◽  
...  
Keyword(s):  
High Risk ◽  
Arsenic Trioxide ◽  
Research Funding ◽  
Primary Study ◽  
Intermediate Risk ◽  
Off Label Use ◽  
Front Line ◽  
Off Label ◽  
Label Use ◽  
Line Management

Abstract Background: We recently showed that the combination of ATRA and arsenic trioxide (ATO) is at least not inferior and possibly superior to standard ATRA and chemotherapy (CHT) in the front-line management of low/intermediate risk APL (Italian-German APL 0406 trial; Lo-Coco et al., NEJM 2013). We report herein on the extended and final series of 276 patients (162 were in the previous report) with the last case being enrolled into the study in January 2013. Methods: The APL0406 study was a prospective, open-label, randomized intergroup trial conducted by the Italian GIMEMA and the German SAL and AMLSG study groups. Eligible patients were adults aged 18-<71 years with newly diagnosed, genetically confirmed, non-high-risk (WBC≤10x109/L) APL. Patients were randomized to receive the ATO+ATRA combination originally developed by the MD Anderson Cancer Center group, or the Italian AIDA2000 protocol (Estey et al., Blood 2006 and Lo-Coco et al., Blood 2010). Patients in the ATRA-ATO arm received ATO 0.15/kg plus ATRA 45 mg/m2 daily until CR, then ATO 5 days/week, 4 weeks on 4 weeks off, for a total of 4 courses and ATRA 2 weeks on and 2 weeks off for a total of 7 courses. Patients in the ATRA-CHT arm received the standard AIDA (ATRA+Idarubicin) induction followed by 3 cycles of anthracycline-based consolidation together with ATRA and low dose CHT and ATRA for maintenance. The primary study objective was EFS at 2 years. Results: A total of 254 patients were evaluable for response to induction. CR was achieved in 122/122 (100%) in the ATRA-ATO versus 128/132 (97%) in the ATRA-CHT arm (P=0.12). Four patients died during induction in the ATRA-CHT arm. After a median follow-up of 36 months (range 1-75 months), the 2-year EFS was 98% and 84.9% in the ATRA-ATO and ATRA-CHT groups respectively (P= 0.0002), The 2-year cumulative incidence of relapse (CIR) rate was 1.1% and 9.4%, respectively (P=0.005) and, finally, the 2-year overall survival (OS) rate was 99.1% vs. 94.4% (P=0.01) for ATRA-ATO vs ATRA-CHT, respectively. Conclusions: The data on this extended cohort demonstrate a significantly augmented survival benefit coupled to a higher antileukemic efficacy provided by ATRA-ATO as compared to ATRA-CHT, in low/intermediate risk APL. These results further support ATRA-ATO as the new standard of care in this clinical setting. Figure 1 Figure 1. Disclosures Platzbecker: Teva: Honoraria. Off Label Use: Presentation includes off-label use of arsenic trioxide (ATO) in front-line management of APL. ATO is currently approved in treatment of relapsed APL in the US and Europe. Breccia:Bristol Myers Squibb: Consultancy; Novartis: Consultancy. Fiedler:TEVA: Travel reimbursement for meeting attendance Other. Lübbert:Cephalon / TEVA: Travel support Other. Link:TEVA: Consultancy, Speakers Bureau. Radsak:Celgene: Research Funding. Döhner:TEVA: Research Funding. Schlenk:TEVA: Research Funding, Speakers Bureau. Lo-Coco:TEVA: Honoraria; Lundbeck: Honoraria.

Survival outcomes and practice trends for off-label use of adjuvant targeted therapy in high-risk locoregional renal cell carcinoma

2020 ◽  
Vol 38 (6) ◽  
pp. 604.e1-604.e7 ◽  
Author(s):  
Nicholas H. Chakiryan ◽  
Ann Martinez Acevedo ◽  
Mark A. Garzotto ◽  
Yiyi Chen ◽  
Jen-Jane Liu ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Targeted Therapy ◽  
High Risk ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Survival Outcomes ◽  
Off Label Use ◽  
Off Label ◽  
Label Use

Phase II Study of All-Trans Retinoic Acid (ATRA), Arsenic Trioxide (ATO), with or without Gemtuzumab OzogamIcin (GO) for the Frontline Therapy of Patients with Acute Promyelocytic Leukemia (APL).

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1080-1080 ◽  
Author(s):  
Farhad Ravandi ◽  
Elihu H. Estey ◽  
Jorge E. Cortes ◽  
Susan O'Brien ◽  
Sherry A. Pierce ◽  
...  
Keyword(s):  
High Risk ◽  
Arsenic Trioxide ◽  
Gemtuzumab Ozogamicin ◽  
Off Label Use ◽  
Free Survival ◽  
Off Label ◽  
All Trans Retinoic Acid ◽  
Risk Patients ◽  
Label Use

Abstract Abstract 1080 Background: The role of arsenic trioxide (ATO) in the frontline treatment of patients with acute promyelocytic leukemia (APL) remains unclear with a number of studies reporting high and durable responses with single agent ATO. We have conducted a trial combining all-trans-retinoic acid (ATRA) with ATO with or without gemtuzumab ozogamicin (GO) in patients with previously untreated APL. Patients and methods: From July 2002 to June 2010, 104 patients with newly diagnosed APL were treated with a combination of ATRA plus ATO in two studies. The first cohort of 47 patients received ATRA (45 mg/m2 daily) and ATO (0.15 mg/kg daily beginning on day 10 of ATRA). High-risk patients (White blood cell count [WBC] > 10 × 109/L) received GO 9 mg/m2 on the first day of induction. From July 2007, the second cohort of 57 patients received ATRA (45 mg/m2 daily) and ATO (0.15 mg/kg daily) concomitantly on day one of induction. They also received GO 9 mg/m2 on day 1, if high risk, and any time during induction if the WBC rose to > 30 × 109/L (and more recently if > 10 × 109/L). Monitoring for PML-RARA fusion gene using reverse transcriptase-polymerase chain reaction (RT-PCR) was conducted after induction and throughout consolidation and follow up. The median age for the 104 patients was 46 years (range, 14–81). Their median presenting WBC was 2.7 × 109/L (0.4-131.4 × 109/L) and their median platelet count was 36 × 109/L (range, 7–261 × 109/L). Seventy three (70%) had low risk and 31 (30%) high risk disease (based only on the presentation WBC ≤ or > 10.0 × 109/L). Results: Overall, 102 patients (98%) achieved complete remission (CR) and 2 died during induction. With a median follow-up of 115 weeks (range, 4 to 397 weeks), 94 patients remain alive. The estimated 5-year survival rate was 88% and event-free survival 86%; only 5 of the patients achieving a CR (5%) have relapsed. The median overall survival, remission duration and event-free survival have not been reached (Figure). Thirty six patients have been alive and in remission for more than 3 years and 21 for more than 5 years. Two late deaths (beyond 300 weeks) occurred in CR from unrelated causes. Conclusion: The combination of ATRA and ATO (with or without GO) as initial therapy for APL is highly effective and safe; it can potentially substitute for chemotherapy containing regimens in high and low risk patients. Disclosures: Ravandi: Cephalon: Honoraria, Research Funding, Speakers Bureau. Off Label Use: Off-label use of arsenic trioxide in frontline therapy of APL; off label use of gemtuzumab ozogamicin in APL. Verstovsek:Incyte Corporation: Research Funding.

scholarly journals Off-label Use of High-Risk Cardiovascular Devices

2017 ◽  
Vol 2 (8) ◽  
pp. 832
Author(s):  
Karen E. Joynt ◽  
Daniel B. Kramer
Keyword(s):  
High Risk ◽  
Off Label Use ◽  
Cardiovascular Devices ◽  
Off Label ◽  
Label Use

Indikationsfremde Anwendung von Medikamenten und Medizinprodukten in der Notfallmedizin

2019 ◽  
Vol 14 (04) ◽  
pp. 361-371
Author(s):  
Karl Peter Ittner ◽  
Joachim Koppenberg ◽  
Ute Walter
Keyword(s):  
Off Label Use ◽  
Off Label ◽  
Label Use

ZusammenfassungWenn zugelassene Arzneimittel außerhalb der in der entsprechenden Fachinformation dargelegten Beschreibungen angewendet werden, dann spricht man von einer nicht zulassungskonformen Anwendung oder von einem Off-Label-Use. Wie in fast allen medizinischen Fachgebieten gibt es auch im Rettungsdienst sogenannte Off-Label-Use-Pharmakotherapien. Sofern evidenzbasierte Informationen zu einer nicht zulassungskonformen Anwendung vorliegen, und insbesondere im konkreten Notfall keine zulassungskonforme Möglichkeit besteht, dann ist diese gerechtfertigt. Verwendet ein Notarzt aber ein Medizinprodukt außerhalb der Zulassung, dann stellt er ein neues Produkt her und haftet persönlich bei einem Patientenschaden.

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