FLUOROQUINOLONES IN PEDIATRIC PATIENTS: NO MORE “OFF-LABEL USE”

2015 ◽  
Vol 101 (1) ◽  
pp. e1.54-e1
Author(s):  
Natalie Dinavitser ◽  
Maya Berlin ◽  
Reuven Miller ◽  
Victoriya Finkel-Pekarsky ◽  
Matitiahu Berkovitch
Keyword(s):  
Literature Search ◽  
Adverse Reactions ◽  
Pediatric Patients ◽  
Reporting System ◽  
Cartilage Damage ◽  
Tendon Injury ◽  
Off Label Use ◽  
Off Label ◽  
Spontaneous Reports ◽  
Pediatric Use

Fluoroquinolones (FQs) are used in pediatric patients worldwide. However, due to cartilage damage in young animals they are not approved for children under 18 years of age for most indications. Major regulatory authorities such as EMA, FDA, UK, Ireland, NZ and Australia indicate that FQs are contraindicated in children. Ciprofloxacin and levofloxacin can be prescribed to children, but only for a few indications. As a result, FQs are used “off-label” in this population. From our experience, we believe that FQs should not be contraindicated in children. However, evidence-based data is needed.ObjectiveTo investigate whether FQ use in children may cause musculoskeletal adverse reactions (ADRs).MethodsWe reviewed the Israel Ministry of Health ADR reporting system and VigiLyze (WHO reporting system) for musculoskeletal ADRs due to FQs in children. A literature search– Medline, Pubmed, Cochraine database and pharmacologic textbooks, for musculoskeletal ADRs among FQ treated pediatric patients was conducted. Terms used: Fluoroquinolones, ciprofloxacin, levofloxacin, ofloxacin, arthropathy, tendinophaty, arthralgia, children, pediatric use.ResultsDuring the period 1968 to Feb 2015, the Israeli MOH did not receive spontaneous reports regarding FQs in children. The VigiLyze program identified 192 ADR reports in children related to FQs: arthralgia, arthropathy, myalgia, and tendon injury. Most ADRs were transient and reversible. The literature search indicated that although musculoskeletal ADRs are not uncommon, they are mild, transient, and not necessarily due to FQs. Joint MRI, performed in some of the studies, did not reveal cartilage damage.ConclusionsFQs should be registered for pediatric patients as for adults.

Remdesivir and Hydroxychloroquine: A Compassionate Use in Covid-19

2020 ◽  
Vol 21 ◽  
Author(s):  
Amritpal Kaur ◽  
Gaurav Chaudhary ◽  
Pargat Singh ◽  
Sandeep Arora ◽  
Rajwinder Kaur
Keyword(s):  
Literature Search ◽  
Review Paper ◽  
Off Label Use ◽  
Compassionate Use ◽  
Off Label ◽  
Parenteral Route ◽  
Randomized Controlled ◽  
Novel Coronavirus ◽  
Microsoft Office ◽  
Antiparasitic Agents

Objective:: Early in December 2019, a mass of sufferers with Novel Coronavirus Pneumonia (SAS-CoV-19) in Wuhan (China) roused worldwide concern. Hardly any drugs showed the light of hope concerning the depletion in the period of treatment and virological suppression is troubled. Furthermore, numerous sufferers have undergone off-label use or compassionate use treatments as well as antiretroviral, antiparasitic agents, anti-inflammatory compounds, and convales-cent plasma in either oral/parenteral route. This study aims to compile and analyze the efficient value of Remdesivir and Hydroxychloroquine and give an insight to their drug profile in the treatment and management of COVID-19 patients. Method:: The literature search from PubMed, Crossref, Springer, Bentham Sciences, Google Scholar, DOAJ, ScienceDirect, and MEDLINE by using keywords like COVID-19, SAS-COV-2, Remdesivir, and hydroxychloroquine was done and ap-propriate peer-reviewed review articles, as well as research articles, were included and compiled in this review paper. The figures were prepared by using ChemOffice 2016 (ChemDraw Professional 2016) and Microsoft Office. Results:: The results of this study indicate that remdesivir in 5/10 studies from collected literature show a reduction in time of recovery and 5/10 shows no variance and having limitations. However, 6/12 shows an increase in the survival/reduction in time of recovery and 6/12 shows no effect or has limitations in the case of hydroxychloroquine. Conclusion:: There is a need to assess more pharmacokinetics and randomized controlled trials (RCT) for both remdesivir and hydroxychloroquine. Furthermore, studies should be conducted in different combinations along with hydroxychloro-quine and remdesivir to get efficient results.

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

Hydroxyurea Therapy Requires HbF Induction for Clinical Benefit in a Sickle Cell Mouse Model.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 817-817
Author(s):  
Jeffrey D. Lebensburger ◽  
Tamara I Pestina ◽  
Kelli Boyd ◽  
Russell E. Ware ◽  
Derek Persons
Keyword(s):  
Gene Therapy ◽  
Sickle Cell ◽  
Pediatric Patients ◽  
Organ Damage ◽  
Off Label Use ◽  
Cell Disease ◽  
Off Label ◽  
Cell Gene ◽  
Stem Cell Gene ◽  
Hydroxyurea Therapy

Abstract Abstract 817 PURPOSE: To evaluate whether there are clinical benefits from chronic hydroxyurea administration that are independent of HbF induction using a murine SCD model in which fetal hemoglobin (HbF) cannot be induced. METHODS: Cohorts of sex- and aged-matched SCD mice were generated by transplanting lethally irradiated C57/BL6 mice with bone marrow from BERK mice. Only mice fully engrafted with SCD hematopoiesis were used for study. Transplanted SCD mice were injected by intraperitoneal route five days per week. SCD mice with high levels of HbF were generated by stem cell gene transfer using a gamma-globin lentiviral vector followed by transplantation. RESULTS: We identified a dose of hydroxyurea (50 mg/kg) that would lead to a stable, well-tolerated reduction in neutrophil count, much like what is done to titrate dosage in human patients with SCD. Hydroxyurea dosed at 25 mg/kg produced no difference in blood counts compared to control mice, while 75 mg/kg and 100 mg/kg both produced critical pancytopenia. As expected, cellulose acetate gel electrophoresis and HPLC analysis showed that HbF was undetectable in both hydroxyurea-treated and saline-treated mice. Based on this dose-finding data, we treated SCD mice with 50 mg/kg hydroxyurea (n=20) and saline (n=13) five days/week for 20 weeks in order to determine whether chronic hydroxyurea therapy could improve both the anemia and organ damage of SCD. Blood counts obtained after 10 weeks again demonstrated a reduction in white blood cells (26.1 vs. 31.2 ×109/L, p<0.005), absolute neutrophil counts (2.9 vs. 4.6 ×109/L, p<0.005), platelets (780 vs 870 × 109/L, p<0.05), without improvement in the anemia (6.7 vs 6.6 g/dL). Consistent with this data, the serum LDH and total bilirubin values remained elevated, similar to control mice, suggesting no improvement in the rate of hemolysis. Necropsy and pathologic analyses of major organs were performed on six mice from each group after 18-20 weeks of hydroxyurea therapy. Hydroxyurea-treated mice showed no improvement in the severe, multi-organ damage, compared to saline-treated, control mice. In contrast, six SCD mice with high levels of HbF resulting from stem cell gene transfer but not treated with hydroxyurea had a significant correction of their anemia (10.8 g/dL) along with a reduction in both total white blood cell (11.7 ×109/L) and absolute neutrophil counts (2.6 × 109/L). The reduction in the neutrophil count secondary to the correction of the anemia by gene therapy was similar to the levels demonstrated with hydroxyurea administration (hydroxyurea ANC 2.9 × 109/L vs. gene therapy ANC 2.6 × 109/L). Importantly, the SCD mice with high HbF demonstrated no significant organ damage. CONCLUSIONS: Despite causing a significant reduction in the leukocytosis and thrombocytosis, hydroxyurea treatment did not improve the severe anemia and multi-organ disease pathology in SCD mice. In contrast, SCD mice with high levels of HbF resulting from stem cell gene therapy showed resolution of both the anemia and organ pathology. These data suggest that induction of HbF is a necessary and major contributor to the beneficial effects of hydroxyurea in SCD. Disclosures: Off Label Use: Hydroxyurea use in pediatric patients sickle cell disease. This abstract does not discuss the off label use of Hydroxyurea in pediatric patients with sickle cell disease. However, discussion of this abstract would likely result in referencing the off label use of hydroxyurea in pediatric patients with sickle cell disease.

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 Analysis of the Safety Profile of Commonly Used Procoagulants Using the FDA Adverse Event Reporting System

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4712-4712
Author(s):  
Emma P. Deloughery ◽  
Joseph J. Shatzel
Keyword(s):  
Adverse Event ◽  
Adverse Events ◽  
Vitamin K ◽  
Reporting System ◽  
Adverse Event Reporting System ◽  
Adverse Event Reporting ◽  
Off Label Use ◽  
Event Reporting ◽  
Off Label ◽  
Events Data

Abstract Introduction: Though less commonly used than their anticoagulant counterparts, procoagulants have an important role in the reversal of anticoagulation. Four-factor prothrombin complex concentrate (4PCC) is now approved by the U.S. Food & Drug Administration (FDA) for the reversal of major bleeding associated with warfarin, and is often used off-label to reverse direct oral anticoagulants. Three-factor concentrate (3PCC) and off-label use of recombinant activated factor VII (rFVIIa) have filled this role in the past. Vitamin K is also used as a common antidote for warfarin-induced coagulopathy. Comparative data evaluating the safety profiles and relative thrombotic risks of the PCCs and rFVIIa is limited. In order to better evaluate their comparative safety we calculated the rate of adverse events reported to the FDA of each procoagulant. Methods: We evaluated the FDA Adverse Event Reporting System (FAERS) database, which compiles drug-related adverse events reported to the FDA from 1969 onwards, to assess the rate of adverse events reported with various procoagulants. Safety profiles were assessed using proportional reporting ratios (PRR) with the total number of reported cases as the denominator. Adverse events data for each drug (vitamin K, rFVIIa, 3PCC, 4PCC) was gathered from FAERS. Both generic and brand names were used to query the database. Adverse events data was filtered by including only events reported by healthcare professionals. Specific adverse events were chosen apriori based on hypothesized potential complications and included hemorrhagic and thrombotic complications. The PRR with 95% confidence interval was generated for each event, with a cut-off of 2 being used to identify associations. Results: As shown in Table 1 and Figure 1, rFVIIa was associated with increased reports of mortality while 4PCC was associated with ischemic stroke, and all but rFVIIa were associated with high INR. 3PCC displayed an increased association with reports of intracranial hemorrhage (ICH), although there was a low rate of reports for 3PCC. Lesser associations were found between rFVIIa and myocardial infarction (MI), 3PCC and deep-vein thrombosis (DVT), and 4PCC and DVT and ICH. In general, vitamin K had the weakest associations among adverse events. Conclusions: Our analysis found that the rate of reports of death and MI were higher with rFVIIa than other procoagulants, while reports of ischemic stroke and intracranial hemorrhage were more common with PCCs. rFVIIa has been associated with cardiovascular before, a finding reiterated by our study. There are notable limitations of this type of analysis, including the reliance on the accurate reporting of adverse events to the FDA, possibility of duplications of reports in the FAERS database, and the importance of not conflating correlation with causation as it relates to these events. The association between rFVIIa and increased death may be due to rFVIIa's history of off-label use in trauma patients and other patient groups at higher risk for mortality. While 4PCC may be the procoagulant of the present, it does not have a perfect safety profile, and further study is needed to better characterize the complications of 4PCC and ensure that it is used in such a way as to not under- or over-treat the condition. Disclosures No relevant conflicts of interest to declare.

scholarly journals A brief analysis of parenteral medicines delivered in community pharmacies for off-label use in pediatric

2021 ◽  
Vol 57 (2) ◽  
pp. 99-105
Author(s):  
Elena DINTE ◽  
◽  
Dana MATEI ◽  
Teodora ZEHAN ◽  
◽  
...  
Keyword(s):  
Pharmaceutical Preparations ◽  
Oral Route ◽  
Active Principle ◽  
Original Form ◽  
Community Pharmacies ◽  
Off Label Use ◽  
Off Label ◽  
Routes Of Administration ◽  
Pediatric Use ◽  
Label Use

Objectives. The current paper aims to obtain an overview regarding the use of parenteral medicines recommended for the pediatric sector and delivered in Romanian community pharmacies. Materials and methods. A retrospective observational study was developed, based on a questionnaire which was distributed in community pharmacies in Romania. Results. The parenteral medicines were delivered in 100 community pharmacies which partake in the study, and which are distributed in 22 counties in Romania. The total number of parenteral medicines considered in the study were aimed for pediatric use and they represented approximately 5% of the total number of medicines prescribed for children delivered in the respective pharmacies. Of these, most of them are medicines authorized for adults, delivered for off-label use, by other routes of administration, in their original form or reformulated in the form of other pharmaceutical preparations, during the compounding activity in the pharmacy. Conclusions. The parenteral medications most prescribed for pediatric use and delivered in community pharmacies are injectable solutions and powders for parenteral use. They are used as off-label medication in children, by other routes of administration, both to capitalize the therapeutic action of the active principle, and also as a vehicle for other medications with oral route or external route of administration.

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

Tigecycline Use in Neonates: 5-Year Experience of a Tertiary Center

2018 ◽  
Vol 14 (03) ◽  
pp. 103-107 ◽  
Author(s):  
Mehmet Gunel ◽  
Erdal Ozbek ◽  
Mehmet İpek
Keyword(s):  
Pediatric Patients ◽  
Newborn Infants ◽  
Drug Resistant ◽  
Efficacy And Safety ◽  
Off Label Use ◽  
Off Label ◽  
Extensively Drug Resistant ◽  
Serious Infections ◽  
Tertiary Center ◽  
Alternative Drugs

AbstractThe off-label use of tigecycline to treat serious infections has been reported in pediatric patients. We report four newborn infants diagnosed with sepsis caused by extensively drug-resistant Klebsiella pneumoniae and successfully treated with tigecycline. If no alternative drugs are available, tigecycline may be considered as an option for nosocomial infections even in newborn infants. However, further reports are needed to establish its efficacy and safety.

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