scholarly journals Medication Repurposing in Pediatric Patients: Teaching Old Drugs New Tricks

2016 ◽  
Vol 21 (1) ◽  
pp. 36-53 ◽  
Author(s):  
Martha M. Rumore
Keyword(s):  
New York ◽  
Pediatric Patients ◽  
Drug Repurposing ◽  
Evidence Based ◽  
Off Label Use ◽  
Level Of Evidence ◽  
Off Label ◽  
Pediatric Age Group ◽  
Evidence Quality ◽  
Label Use

OBJECTIVES: Gaps in pediatric therapeutics often result in off-label use and specifically, novel uses for existing medications, termed “drug repurposing.” Drug Information (DI) queries to a Pediatric Medication Resource Center of a large metropolitan pediatric hospital in New York and inherent difficulties in retrieving evidence-based information prompted a review of current medication repurposing for pediatric patients. The objective included characterization of innovative off-label use of medications Food and Drug Administration (FDA)-approved for 1 or more indications to treat a totally different disorder or indication in pediatric patients. METHODS: A systematic literature review was conducted to retrieve publications describing repurposed medications in pediatric patients. Excluded was FDA-approved indications used off-label in pediatric patients (e.g., different dose), preclinical data, adult use only, and experimental use. Evidence quality was classified using a modified American Academy of Neurology Level of Evidence. Results were analyzed using χ2 at p < 0.05. RESULTS: Over 2000 references were retrieved and reviewed. A total of 101 medications repurposed for novel off-label uses for pediatric patients were identified: 38 for neonates, 74 for children, and 52 for adolescents. Neonates and infants were least likely to receive a medication for a repurposed use. Strong or intermediate evidence existed in 80.2% of cases. The evidence was weak in 19.8%. No significant relationship was observed between the pediatric age group and strength of the literature. Most repurposed uses pertained to generic or widely used medications. Less than 5% of medications were first marketed after 2011. CONCLUSIONS: While not exhaustive, the present study represents the most comprehensive listing of novel uses exclusive to pediatric patients. Further research is needed to identify the frequency of repurposed uses. The valuable DI role of pharmacists in assessing repurposed uses is of expanding and increasing importance to ensure such uses are evidence-based.

scholarly journals Contrasting evidence to reimbursement reality for off-label use (OLU) of drug treatments in cancer care: rationale and design of the CEIT-OLU project

ESMO Open ◽  
2019 ◽  
Vol 4 (6) ◽  
pp. e000596
Author(s):  
Amanda Katherina Herbrand ◽  
Andreas Michael Schmitt ◽  
Matthias Briel ◽  
Stefan Diem ◽  
Hannah Ewald ◽  
...  
Keyword(s):  
Cancer Care ◽  
Clinical Evidence ◽  
Patient Characteristics ◽  
Evidence Based ◽  
Cancer Drugs ◽  
Off Label Use ◽  
Level Of Evidence ◽  
Treatment Benefit ◽  
Off Label ◽  
Label Use

BackgroundOff-label use (OLU) of a drug reflects a perceived unmet medical need, which is common in oncology. Cancer drugs are often highly expensive and their reimbursement is a challenge for many healthcare systems. OLU is frequently regulated by reimbursement restrictions. For evidence-based healthcare, treatment ought to be reimbursed if there is sufficient clinical evidence for treatment benefit independently of patient factors not related to the treatment indication. However, little is known about the reality of OLU reimbursement and its association with the underlying clinical evidence. Here, we aim to investigate the relationship of reimbursement decisions with the underlying clinical evidence.Methods/ designWe will extract patient characteristics and details on treatment and reimbursement of cancer drugs from over 3000 patients treated in three Swiss hospitals. We will systematically search for clinical trial evidence on benefits associated with OLU in the most common indications. We will describe the prevalence of OLU in Switzerland and its reimbursement in cancer care, and use multivariable logistic regression techniques to investigate the association of approval/rejection of a reimbursement requests to the evidence on treatment effects and to further factors, including type of drug, molecular predictive markers and the health insurer.DiscussionOur study will provide a systematic overview and assessment of OLU and its reimbursement reality in Switzerland. We may provide a better understanding of the access to cancer care that is regulated by health insurers and we hope to identify factors that determine the level of evidence-based cancer care in a highly diverse western healthcare system.

Survey on Off-Label Use of Antineoplastic Agents in Pediatric Patients using a Large-scale Medical Database in Japan

2020 ◽  
Vol 51 (6) ◽  
pp. 307-316
Author(s):  
Mayuko KURODA ◽  
Ayaka NAKAMURA ◽  
Nanae TANEMURA ◽  
Masayoshi NAKAKUNI ◽  
Junko SATO ◽  
...  
Keyword(s):  
Antineoplastic Agents ◽  
Large Scale ◽  
Pediatric Patients ◽  
Off Label Use ◽  
Medical Database ◽  
Off Label ◽  
Label Use

Off-Label Antithrombin Use In Pediatrics: Evaluation Of Safety, Efficacy and Usage Patterns

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1137-1137 ◽  
Author(s):  
Rosa Diaz ◽  
Brady S Moffet ◽  
Donald Mahoney ◽  
Donald L Yee
Keyword(s):  
Pediatric Patients ◽  
Heparin Therapy ◽  
Activity Level ◽  
Ventricular Assist Devices ◽  
Bleeding Complications ◽  
Off Label Use ◽  
Bleeding Events ◽  
Off Label ◽  
Heparin Resistance ◽  
Label Use

Abstract Background Antithrombin (AT) is a naturally occurring anticoagulant, and occupies a critical role in regulating thrombin generation. AT concentrate (ATC) is indicated for patients with hereditary AT deficiency but off-label use for acquired heparin resistance in patients receiving anticoagulation for thrombotic disease is not uncommon. Use of ATC in children in this and other settings such as extracorporeal membrane oxygenation (ECMO) and ventricular assist devices (VAD) appears to be expanding. However, no guidelines exist with respect to proper indications and monitoring, and scant safety and efficacy data is available. The objective of this study was to review our substantial institutional experience with off-label pediatric use of ATC regarding indications for use, dosing practice, dosing effect, adverse events, and patient outcomes. Methods An institutional review board (IRB)-approved retrospective chart review is being performed on all pediatric patients who received human-plasma derived ATC at Texas Children’s Hospital from 2001 to 2013. Data collection includes demographic, clinical and laboratory data. We are currently reporting on the first 100 consecutive patients examined using descriptive statistics and ANOVA for group comparisons. Results One hundred patients with median age 5 months (range 0 to 216 months) received 536 doses of ATC (median 4 doses per patient, range 1 to 29) between February 2012 and May 2013. Clinical scenarios for ATC use included heparin (unfractionated (UFH) or low molecular weight (LMWH)) therapy for thrombosis in 47%, ECMO in 38%, VAD in 5% and other settings in 10% of the 100 consecutive patients analyzed. Neither dosing nor dose response (measured as AT activity level post- versus pre-ATC dose) differed significantly between these patient groups. For the group of patients who received AT for thrombosis and heparin therapy, only 57% had subtherapeutic levels (anti-Xa activity <0.3 units/mL for UFH or <0.5 units/mL for LMWH) at the time of ATC initiation. Of these, only 22% achieved therapeutic levels within 12 hours after the first ATC dose. Among all the groups, 33% of children had bleeding events within 72 hours after ATC administration, most commonly reported as oozing from line sites (n=15). There was no association between AT activity levels measured after ATC administration and bleeding events. The 2 patients that developed intracranial hemorrhage were on ECMO. There were no allergic reactions. End of hospitalization mortality was 28%. Conclusion In this high-risk cohort of pediatric patients, off-label ATC was most commonly given in the setting of heparin therapy for thrombosis and low AT levels, but often without apparent evidence for inadequate heparinization as measured by low anti-Xa activity. Although ATC administration led to a significant rise in AT activity for most patients, interindividual response to ATC varied greatly, with some patients demonstrating little to no response. Furthermore, among patients who exhibited clear signs of heparin resistance, the first administration of ATC potentiated an adequate heparin effect in only a small minority. Finally, ATC administration was associated with high rate of minor bleeding complications and rare major bleeding events. These findings raise significant questions about the safety, efficacy and appropriate use of ATC in pediatrics and highlight the need for its further prospective study. Disclosures: Off Label Use: Antithrombin concentrate.

scholarly journals Off-Label Medicine Use in Pediatric Inpatients: A Prospective Observational Study at a Tertiary Care Hospital in India

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Mohd Masnoon Saiyed ◽  
Tarachand Lalwani ◽  
Devang Rana
Keyword(s):  
Observational Study ◽  
Prospective Observational Study ◽  
Pediatric Patients ◽  
Tertiary Care Hospital ◽  
Tertiary Care ◽  
Quality Data ◽  
Care Hospital ◽  
Off Label Use ◽  
Off Label ◽  
Label Use

Background. In the absence of standard pediatric prescribing information, clinicians often use medicines in an off-label way. Many studies have been published across the globe reporting different rates of off-label use. There is currently no study based on Indian drug formulary.Methods. The prospective observational study included pediatric patients in ages between 0 and 12 years admitted in a tertiary care hospital. Off-label use was assessed using the National Formulary of India (NFI). Predictors of off-label use were determined by logistic regression.Results. Of the 1645 medications prescribed, 1152 (70%) were off-label based on 14 possible off-label categories. Off-label medicines were mainly due to dose difference and use in restricted age limits as indicated in NFI. Respiratory medicines (82%), anti-infectives (73%), and nervous system medicines (53%) had higher off-label use. Important predictors of off-label prescribing were pediatric patients in age of 0 to 2 years (OR 1.68, 95% CI;P<0.001) and hospital stay of six to 10 days (OR 1.91, 95% CI;P<0.001).Conclusion. Off-label prescribing is common among pediatric patients. There is need to generate more quality data on the safety and efficacy of off-label medicines to rationalize pediatric pharmacotherapy.

Trends in the off‐label use of β‐blockers in pediatric patients

2019 ◽  
Vol 61 (11) ◽  
pp. 1071-1080
Author(s):  
Vishal R Kaley ◽  
E Oliver Aregullin ◽  
Bennett P Samuel ◽  
Joseph J Vettukattil
Keyword(s):  
Pediatric Patients ◽  
Off Label Use ◽  
Off Label ◽  
Β Blockers ◽  
Label Use

scholarly journals Off-Label Use of the Female Condom for Anal Intercourse Among Men in New York City

2011 ◽  
Vol 101 (12) ◽  
pp. 2241-2244 ◽  
Author(s):  
Elizabeth A. Kelvin ◽  
Joanne E. Mantell ◽  
Norman Candelario ◽  
Susie Hoffman ◽  
Theresa M. Exner ◽  
...  
Keyword(s):  
New York ◽  
New York City ◽  
York City ◽  
Anal Intercourse ◽  
Female Condom ◽  
Off Label Use ◽  
Off Label ◽  
Label Use

scholarly journals Phase 1/2 Study in Pediatric Patients with Relapsed/Refractory B-Cell Precursor Acute Lymphoblastic Leukemia (BCP-ALL) Receiving Blinatumomab Treatment

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2292-2292 ◽  
Author(s):  
Arend von Stackelberg ◽  
Franco Locatelli ◽  
Gerhard Zugmaier ◽  
Rupert Handgretinger ◽  
Tanya M. Trippett ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Pediatric Patients ◽  
Phase 1 ◽  
Adult Patients ◽  
Off Label Use ◽  
Employment Equity ◽  
Hematopoietic Stem ◽  
Off Label ◽  
Equity Ownership ◽  
Label Use

Abstract Introduction: Blinatumomab, an investigational bispecific T-cell engager (BiTE®) antibody construct, has been shown to induce remission in adult patients with relapsed/refractory BCP-ALL. Medically important adverse events (AEs) related to blinatumomab treatment in adults are cytokine release syndrome (CRS) and neurological events. We report the primary analysis of the phase 1 portion of a multicenter phase 1/2 study of blinatumomab in pediatric patients with relapsed/refractory BCP-ALL. Methods: In this continuing study, eligible patients are <18 years old and must have BCP-ALL that is in second or later bone marrow relapse, in any marrow relapse after allogeneic hematopoietic stem cell transplantation (HSCT), or refractory to induction or reinduction therapy. Patients receive blinatumomab for 28 days by continuous intravenous infusion followed by a 14-day treatment-free period (for up to five cycles). Escalating dosing levels of 5, 15, and 30 μg/m²/day and stepwise dosing of 5–15 or 15–30 μg/m²/day were evaluated. The primary endpoint of the phase 1 portion of the study was maximum tolerated dose (MTD). Secondary endpoints included toxicity, complete remission (CR) rate, overall survival (OS), relapse-free survival (RFS), pharmacokinetics evaluation, and cytokine measurement. Results: In the phase 1 portion, 41 patients received a total of 73 cycles (median of 2 cycles received, range of 1 to 5). Eight (20%) patients had refractory disease and seven (17%) had experienced at least two bone marrow relapses. Twenty-six (63%) patients had relapsed following HSCT. Dose-limiting toxicities (DLTs) are listed in Table 1. The MTD was established at 15 µg/m²/day. To decrease the risk of CRS, a stepwise dose of 5–15 μg/m²/day was recommended for the phase 2 part of the study (5 µg/m²/day for 7 days, then 15 µg/m²/day). This dose was subsequently assessed in two age groups (2–6 and 7–17 years) in the phase 1 expansion part with one of 18 patients developing grade 3 CRS. No patient in the expansion cohort developed grade 4 or 5 CRS. Across all dosing levels, 13 (32%) patients had CR with 10 (77%) achieving minimal residual disease (MRD) negativity. Of these 13 patients, nine (69%) underwent HSCT. Among patients who achieved CR, median RFS was 8.3 months (95% CI: 3.0–16.0 months). Median OS was 5.7 months (95% CI: 3.3–9.7 months; Figure 1) with a median follow-up time of 12.4 months. Across all dosing levels, the most common AEs regardless of causality were pyrexia (78%), headache (37%), hypertension (32%), nausea (29%), abdominal pain (27%), pain in the extremity (27%), and anemia (27%). Pharmacokinetic parameters, including steady-state concentration (Css), clearance, and half-life were similar to those from adult patients with relapsed/refractory BCP-ALL who received body surface area-based blinatumomab dosing. Transient elevations of serum cytokines were observed mostly within the first two days after starting blinatumomab, in particular IL-6, IFN-gamma, IL-10, and, to a lesser extent, IL-2 and TNF-α. Conclusions: In the phase 1 portion of this study in pediatric patients with relapsed/refractory BCP-ALL, the MTD was 15 µg/m²/day. CRS was dose-limiting, but stepwise dosing of 5–15 μg/m²/day has been effective in ameliorating CRS. Thirty-two percent of patients achieved CR and more than half were able to proceed to allogeneic HSCT. Figure 1 Figure 1. Disclosures von Stackelberg: Amgen: Consultancy, Honoraria. Off Label Use: This presentation will discuss the off-label use of blinatumomab, as this agent is not approved for use by the FDA, EMA or any other regulatory authorities.. Zugmaier:Amgen Inc.: Equity Ownership; Amgen Research (Munich) GmbH: Employment. Rheingold:Novartis: Consultancy. Hu:Amgen Inc.: Employment, Equity Ownership. Mergen:Amgen Inc.: Equity Ownership; Amgen Research (Munich) GmbH: Employment. Fischer:Amgen Inc.: Equity Ownership; Amgen Research (Munich) GmbH: Employment. Zhu:Amgen Inc.: Employment, Equity Ownership. Hijazi:Amgen Inc.: Equity Ownership; Amgen Research (Munich) GmbH: Employment. Gore:Amgen Inc.: Travel Support Other.

Off-label drug use in home palliative care: A non-evidence-based established practice.

2017 ◽  
Vol 35 (31_suppl) ◽  
pp. 225-225
Author(s):  
Laura Velutti ◽  
Carlotta Pavesi ◽  
Diego Lopane ◽  
Concetta Arcanà ◽  
Annalisa Saetta ◽  
...  
Keyword(s):  
Palliative Care ◽  
Retrospective Analysis ◽  
Evidence Based ◽  
Care Pathways ◽  
Administration Route ◽  
Off Label Use ◽  
Off Label ◽  
Treatment Interruptions ◽  
Infusion Duration ◽  
Label Use

225 Background: Advanced cancer patients (pts) often present with multiple concomitant symptoms and off-label use of drugs (indications doses formulations administration route) is a common practice. Drugs mixture (DM) solutions by continuous administration are frequently used. However, evidence-based data in this setting is scarce. Methods: We performed a retrospective analysis of 576 consecutive care pathways provided by our Home Palliative Care (HC) Service from Jul 2010 to Jun 2017. Infusions were administered subcutaneously (sc) or by a venous (iv) access, by elastomeric pumps (EP) (5 days - 2 mL/h) with drugs diluted in 0.9% NaCl with no light protection. We analyzed: treated symptoms, drugs, doses/concentrations, solution transparency, administration route, infusion duration, clinical response, adverse events (AEs), compliance/treatment acceptability, device proper functioning, and treatment interruptions. Results: We analyzed 266 pts out of 576 care pathways treated with DM infusions, M/F 143/123, median age 70 yrs (21-92); treated symptoms: pain (50%), nausea/vomiting (20%), dyspnea/agitation (20%), dysphagia/mucositis (18%); infused drugs: morphine, midazolam, dexamethasone, ranitidine, metoclopramide, scopolamine, alizapride, haloperidol, furosemide, and ketorolac. Median number of drugs in the DM was 3 (1-6). Administration route was sc in 214 pts/80%, iv in 52 pts/20%. Median infusion duration was 5 days (0-64). Symptoms control was achieved within 72 h in 69% of pts. No AEs related to the infusion devices were observed. Compliance was good in 92% of pts, poor/inadequate in 8%. 5 EP malfunctions were observed: 1 human error, 1 device obstruction due to furosemide flocculation, 3 unexplained. Also, 3 pts required sc infusion interruption due to fluid accumulation near the injection site. Conclusions: This retrospective analysis on a large number of pts shows efficacy and tolerability of DM administration by EP in the HC setting. Treatment compliance was high, no AEs were observed, EP malfunction and therapy discontinuation were rare. However, there are still many open questions about the off-label use of drugs in this setting, and prospective trials are strongly suggested.

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