Rates Of Off-label Use Research Articles

Low-dose ketamine infusions for chronic pain management: Does this qualify as evidence-based practice?

Chronic pain is becoming increasingly prevalent and burdensome both worldwide and in the United Kingdom. Due to the complexity of chronic pain and the therapeutic challenge associated, management is often difficult and requires multidisciplinary care encompassing a combination of pharmacological and non-pharmacological strategies. Conventional analgesic treatments, such as opioids and anticonvulsants, are effective in less than half of chronic pain sufferers and are typically limited to short-term use to prevent complications associated with long-term use such as tolerance and dependence. Consequently, research and clinical interest in alternative management options for chronic pain have increased in recent years, with ketamine being one example under investigation. However, since ketamine has been licensed as an anaesthetic for decades, it has bypassed the traditional scrutinous drug development sequence that is typically seen for therapeutics marketed for pain. As such, data supporting the unlicensed administration of ketamine for chronic pain management is lacking and is being outpaced by the rates of off-label use in pain clinics. Recent limited evidence suggests that ketamine, when given as an intravenous infusion in subanaesthetic doses for refractory pain patients, may provide modest analgesic effects in nearly all aetiologies of chronic pain, with side effects common but typically mild. However, there are concerns over the safety of this practice due to the paucity of robust supportive evidence and the accompanying lack of clinical guidelines or standardised protocols. This review shall summarise the literature examining the use of subanaesthetic-dose ketamine infusions for chronic pain to comment on the current level of evidence, with limitations of existing research and future recommendations discussed.

Rates of psychotropic medicine prescribing in paediatric populations in Australian general practice from 2000-2016

General practitioner (GP) prescribing of psychotropic medicines to paediatric patients is increasing across countries, sparking the need for additional research into this field. We examined prescribing rates, GP and patient characteristics and indications associated with prescribing psychotropic medicines to paediatric patients in Australian general practice, using data from the Bettering the Evaluation and Care of Health (BEACH) program. We extracted all encounters with children aged 3 to 17 from 2000 to 2016. Psychotropic medicines were defined as those in the ATC codes N05 (Psycholeptics) and N06 (Psychoanaleptics). Of the 144,397 encounters, GPs prescribed 1829 psychotropic medicines to paediatric patients at an average rate of 1.16 prescriptions per 100 encounters (95% confidence interval 1.09-1.23). We found that the rate of psychotropic medicines prescribed to paediatric patients in Australian general practice increased. Patients who were adolescent, female, socio-economically disadvantaged or from an English-speaking background were significantly more likely to be prescribed a psychotropic medicine. GP practices in remote or regional areas and Australian graduate GPs were more likely to prescribe psychotropic medicines to paediatric patients. Depression, attention deficit hyperactivity disorder, anxiety and autism were the most common psychiatric indications managed with psychotropic medicines. Antidepressants, psychostimulants, benzodiazepines, antipsychotics and other psychotropic medicines were prescribed, signifying a high rate of off-label use. Sertraline was the most common psychotropic medicine prescribed, followed by fluoxetine and methylphenidate. Future studies involving data from other prescribers, e.g. paediatricians and psychiatrists, and studies linking prescribed medicines to their indications may widen our understanding of psychotropic medicine prescribing in Australian paediatric patients.

Clinicians' Adherence to Guidelines When Initiating Methylphenidate Treatment.

<b><i>Aims:</i></b> Between 2008 and 2012, the number of children and adolescents in the Netherlands who received methylphenidate prescriptions increased by 35.6%. We determined guideline adherence regarding the assessment of attention-deficit/hyperactivity disorder (ADHD) and rates of off-label use in those 2 years. We also compared adherence to guidelines between mental health and pediatrics settings. <b><i>Methods:</i></b> We conducted a medical file audit of 506 children or adolescents who had received a first methylphenidate prescription in 2008 (<i>n</i> = 208) or 2012 (<i>n</i> = 298) across mental health (<i>n</i> = 333) and pediatrics outpatient clinics (<i>n</i> = 173) in the Netherlands and assessed adherence to seven guideline recommendations. <b><i>Results:</i></b> We did not find significant differences between 2008 and 2012 regarding the mean adherence to the seven recommendations (43% vs. 45%) or the percentage of off-label use (35% vs. 30%). Best adherence rates (over the years 2008 and 2012 combined) concerned the assessment of comorbidities (89%) and the involvement of teachers in the diagnostic process (75%). Least frequently adhered to were assessing ADHD severity (1%), the use of a (semi-)structured parent interview (16%), and providing psycho-education to parents (42%) or teachers (1%). Mental health settings showed better adherence than pediatrics settings (over the years 2008 and 2012 combined) concerning the use of (semi-)structured parent interviews (22% vs. 3.1%), having a separate diagnostic session directed at the child (81% vs. 63%), assessment of comorbidities (95% vs. 76%), and providing psycho-education to parents (51% vs. 24%). <b><i>Conclusions:</i></b> There was neither a decrease in adherence to guidelines nor an increase in off-label use between 2008 and 2012. However, there is ample room for improvement regarding guideline adherence.

Epidemiological and Psychopharmacological Study About Off-Label Treatment in Child and Adolescent Psychiatric Emergencies: A Tertiary/Single Center Experience.

The study used an epidemiological and pharmacological description of child and adolescent psychiatric emergencies (CAPEs), during which psychotropic medications are frequently administered as off-label therapies. We retrospectively describe CAPE in 190 patients (mean age, 14.7 years) referring in the emergency department of a single tertiary center, from June 2016 to June 2018, focusing on off-label administration rate, most of all in emergency setting. An intrinsic fragility was observed in this population, where 28.4% of patients present a history of self-harm, 24.7% a concomitant neurodevelopmental disorder, and 17.3% a history of substance abuse. Psychomotor agitation was the most frequent referral reason, and it represents an unspecified clinical presentation of several conditions, while self-harm showed a stronger association with depressive disorders (55.2%).Globally, 811 medications were administered both as baseline therapy (67.8% of off-label rate) and/or in the emergency setting, where the off-label rate raised to 78.3%. Benzodiazepines had the highest rate of off-label use (98.2% as baseline therapy, 92.9% in acute context). Nevertheless, in 83.5% cases of acute administrations, a singular oral benzodiazepine (mostly lorazepam) guaranteed psychomotor agitation resolution, with a lower rate of adverse effects in contrast with atypical antipsychotics. Off-label drug use in CAPEs is a recurrent clinical practice. An international agreement about off-label drugs is crucial to obtain standard long-term pharmacoepidemiological, safety, and efficacy data. Pharmacological pediatric trials and international guidelines are also required to regulate pharmacological treatments of CAPEs, most of all in emergency settings.

Off-label use in adult palliative care – more common than expected. A retrospective chart review

ObjectiveOff-label drug use seems to be integral to adult palliative care pharmacotherapy. Balancing potential risks and benefits in the context of limited therapeutic options is challenging. To provide specific support...

Off-Label Utilization Trend for Recombinant Factor VIIa in Children's Hospitals in the United States

Background: Recombinant FVIIa (rFVIIa) was approved by the Food and Drug Administration (FDA) as a hemostatic agent in 1999 for the treatment of patients with hemophilia and inhibitory antibodies against either factor VIII or IX and subsequently approved for use in patients with congenital factor VII deficiency and Glanzmann Thrombasthenia refractory to platelet transfusions in 2005 and 2014 respectively. These are rare disorders and the use of rFVIIa in these conditions has been found to be effective and safe. Despite this very narrow indication for usage, rFVIIa is being used for a diverse range of off-label indications. Along with uncertainty regarding clinical efficacy, available data suggests that the risk of thromboembolic events is increased when rFVIIa is used in off-label settings. Studies on the off-label use of rFVIIa in children are limited to a few large case series. In a retrospective multicenter cohort study utilizing the Pediatric Health Information System (PHIS) administrative database, Witmer et al demonstrated a 10-fold increase in the annual rate of off-label admissions from 2000 to 2007. The mortality rate in the off-label group was 34% and thrombotic events occurred in 11% of the off-label admissions. We conducted a follow up study to characterize the evolution of the off-label use of rFVIIa in children. Objective: To describe current trends of off-label utilization and adverse effects of rFVIIa in children. Study design: A retrospective multicenter cohort study utilizing the PHIS administrative database was conducted. The PHIS dataset includes 51 children's hospitals in the United States and is representative of tertiary care centers in the nation. In patients, 18 years of age or younger who received rFVIIa between 2012-2018 were included. A label admission was defined as an admission with an International Classification of Diseases (ICD-9 and ICD-10) diagnostic code for hemophilia, Factor VII deficiency or Glanzmann thrombaesthenia; admissions without these codes were classified as off-label. Data were analyzed descriptively. Results: There were 7,738 number of admissions, representing 6,493 unique individual subjects. A total of 78.3 % of the admissions were off-label. The rate of off-label use was stable at approximately 80% of the admissions from 2012-18. The most frequent admitting services for the off-label admissions included cardiology (29.8%), cardiovascular/thoracic surgery (15.7%), critical care (15.0%), neonatal-perinatal medicine (8.7%), and hematology/oncology (6.1%). Over half (54.6%) of off-label administration occurred in children younger than 1 year old. Among the off-label admissions 57 % were male and the median days of use of rFVIIa was 1 day. The mortality rate in the off-label group was 22.3 %. Thrombotic events occurred in 11.4% of the off-label admissions. Among the off-label admissions with thrombotic events, the most common admitting services were cardiology (35.0%) and critical care (21.2%). Conclusion: We have demonstrated that on a per admission basis the predominant use of rFVIIa is off-label. Thrombotic events are common. Although the mortality rate in the pediatric patients who received off-label rFVIIa is high; its lower when compared with the previous review. This may likely reflect, in part, the severity of illness in this patient group. In the absence of clearly supportive data demonstrating safety and efficacy, restraint should be exercised with careful consideration of risk versus benefit for use of rFVIIa in off-label settings. Disclosures Gupta: Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees; CSL Behring: Research Funding; Takeda-Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. O'Brien:Pfizer: Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding. OffLabel Disclosure: Recombinant FVIIa (rFVIIa) was approved by the Food and Drug Administration (FDA) as a hemostatic agent in 1999 for the treatment of patients with hemophilia and inhibitory antibodies against either factor VIII or IX and subsequently approved for use in patients with congenital factor VII deficiency and Glanzmann Thrombasthenia refractory to platelet transfusions in 2005 and 2014 respectively. These are rare disorders and the use of rFVIIa in these conditions has been found to be effective and safe. Despite this very narrow indication for usage, rFVIIa is being used for a diverse range of off-label indications.

Off-label use of tamoxifen in a Chinese tertiary care hospital.

Background Tamoxifen is an estrogen receptor modulator used for the treatment of breast cancer; however, currently, it is used in many off-label indications. Objective To investigate the prevalence of tamoxifen off-label prescribing and explore available scientific evidence that supports those uses in outpatients. Setting Xiamen maternity and child health care hospital in Xiamen city of China. Method All the prescriptions of outpatients receiving tamoxifen were exported from an electronic prescribing system during a 1-year period. Tamoxifen use was then classified as either on- or off-label according to the criteria we established previously, and the details of the off-label prescriptions were collected. Logistic regression was applied to explore predictive variables. Evidence search was limited to Up-To-Date, the Micromedex database and PubMed. Main outcome measure The rate of off-label use, risk factors identified by logistic regression and evidence exhibition. Results A total of 75% of all the prescriptions available were classified as off-label use. Hyperplasia of the breast was the most frequently prescribed off-label indication. According to the analysis of logistic regression, male patients, patients less than 34years old, and physicians with a higher professional title were more likely associated with off-label prescribing. After a search in Up-To-Date, the Micromedex database and PubMed, only male infertility, atypical hyperplasia, mastodynia, peripheral precocious puberty and gynecomastia were found to have strong evidence supporting the use of tamoxifen off-label (22.75%). Conclusion Although the off-label use of tamoxifen was common in our hospital, there was a relative shortage of evidence available supporting those uses.

Patterns and predictors of off-label prescription of psychiatric drugs.

Off-label prescribing of psychiatric drugs is common, despite lacking strong scientific evidence of efficacy and potentially increasing risk for adverse events. The goal of this study was to characterize prevalence of off-label prescriptions of psychiatric drugs and examine patient and clinician predictors of off-label use. This manuscript presents a retrospective, cross-sectional study using data from the 2012 and 2013 National Ambulatory Medical Care Surveys (NAMCS). The study examined all adult outpatient visits to psychiatric practices for chronic care management with a single listed visit diagnosis in which at least one psychiatric drug was prescribed. The main outcome measure was off-label prescribing of at least one psychiatric drug, defined as prescription for a condition for which it has not been approved for use by the FDA. Among our sample representative of 1.85 billion outpatient visits, 18.5 million (1.3%) visits were to psychiatrists for chronic care management in which at least one psychiatric drug was prescribed. Overall, the rate of off-label use was 12.9% (95% CI: 12.2–15.7). The most common off-label uses were for manic-depressive psychosis treated with citalopram and primary insomnia treated with trazodone. Several patient and clinician characteristics were positively associated with off-label prescribing, including seeing a psychiatrist (OR: 1.06, 95% CI, 1.01–1.12; p = 0.03) instead of another type of clinician, the office visit taking place in the Western region of the country (OR: 1.09, 95% CI, 1.01–1.17; p = 0.02), and the patient having 3 or more chronic conditions (OR: 1.12, 95% CI, 1.02–1.14; p = 0.003). In contrast, having Medicare coverage (OR: 0.93, 95% CI, 0.84–0.97; p = 0.04) and receiving payment assistance from a medical charity (OR: 0.91, 95% CI, 0.88–0.96; p = 0.03) instead of private insurance were negatively associated with off-label prescribing. These results suggest that certain classes of psychiatric medications are being commonly prescribed to treat conditions for which they have not been determined by the FDA to be clinically efficacious and/or safe.

Trends in the "Off-Label" Use of GnRH Agonists Among Pediatric Patients in the United States.

Gonadotropin-releasing hormone (GnRH) agonists are FDA approved for the treatment of precocious puberty. The therapy consists of histrelin acetate (Supprelin), a surgically implanted device, or Lupron injections. In recent years, the use of these agents has been extended to include the off-label treatment of children with normally timed puberty. Trends in the off-label use of GnRH agonists in children across the U.S. have not been previously described in the literature. We analyzed data on the use of Supprelin and Lupron reported to the Pediatric Health Information System (PHIS) from 2013 to 2016 to determine the trends in both the FDA-approved and off-label uses of these medications. We identified a stable cohort of 39 children's hospitals administering GnRH agonist therapies from 2013 to 2016. During this period, the annual number of children treated with these medications for precocious puberty increased modestly, from 283 to 303; meanwhile, the fraction of children receiving therapy for an off-label indication more than doubled, from 12% (39 of 322 total patients) to 29% (125 of 428 total patients). Privately insured patients were more likely to be treated for an off-label indication (13%; 119 out of 883 patients) than Medicaid patients (8%; 58 out of 706 patients; χ2[1] = 10.97, P = .00093). From 2013 to 2016, the proportion of children treated with GnRH agonists for an off-label indication notably increased. The number of children treated for precocious puberty modestly increased. Private insurance coverage was associated with higher rates of off-label use.

State insurance mandates and off-label use of chemotherapy.

Access to cancer drugs used off-label is important to cancer patients but may drive up healthcare costs with little evidence of clinical benefit. We hypothesized that state health insurance mandates for private insurers to provide coverage for off-label use of cancer drugs cause higher rates of off-label use. We used Truven MarketScan data from 1999 to 2007 on utilization of 35 infused chemotherapy drugs in private health plans in the United States, covering the period when eight states implemented off-label coverage laws. We studied trends in off-label use of drugs, distinguishing between appropriate and inappropriate off-label use according to drug compendia, and estimated difference-in-difference regressions of the effect of state laws on off-label use. We estimate 41% of utilization was off-label, including 17% of use conservatively defined as inappropriate. Trends show gradual declines in off-label use over time. We also find no discernable effect of state laws mandating coverage of off-label use of cancer drugs on utilization patterns under multiple empirical specifications. Our conclusion is that policymakers should consider shifting away from mandating coverage as a way to ensure access to drugs off-label and towards incentivizing adherence to clinical practice guidelines to improve the quality and value of off-label use.

Drug utilization study of off-label drug use in outpatient department of psychiatry: a prospective study at a tertiary care teaching hospital

Background: In the absence of standard psychiatric prescribing information, physician often use drugs 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: After taking permission from Institutional Ethics Committee (IEC), a prospective study was conducted among 285 patients attending Psychiatry outpatient department for the period of 4 months. Data related to demographic parameters, diagnosis of psychiatry conditions and drugs details were collected directly from the patient's medical records and entered in Case Record Form (CRF).The off-label drugs were categorized as per National Formulary of India. Multivariate binary logistic regression model was used to determine the predictors of off- label drug prescribing. The data were statistically analyzed using SPSS version 19 and chi-square test.Results: A total of 285 patients (169 males, 116 females) were included in the study with mean age of 36.54±13.91 years. Most of the patients (n=65, 22.8%) were diagnosed as schizophrenic. Out of 285 patients, 133(46.6%) received at least one off-label drug. A total 841 drugs were prescribed out of which 167(19.85%) were off-label. The drug most frequently prescribed as off-label were trihexiphenidyl HCL 29 (10.2%), clozapine 23 (8.1%) and clonazepam 13 (4.6%).Conclusions: Off label drugs used among psychiatry patients was 19.85%. The most frequently used off-label drugs was trihexiphenidyl HCL. The use of off-label drugs in psychiatric patients has been reportedly increasing which warrant national drug regulatory authorities to review and revise safe administration such drugs.

Outpatient antidepressant drug use in children and adolescents in Germany between 2004 and 2011.

Recent studies on the utilization of antidepressant drugs in minors are scarce, methodologically limited, and do not factor in off-label use sufficiently. Beyond that, little is known about the short treatment durations that have been observed for many young antidepressant users. The present study examined antidepressant use in pediatric patients aged 0 to 17 years over time, investigated changes regarding the prescribed drugs, analyzed underlying diagnoses, and assessed the rate of off-label use. We used claims data of roughly two million individuals to calculate annual prevalence and incidence rates of antidepressant prescriptions for the years 2004 to 2011. Analyses were stratified by age, sex, and drug type. For antidepressant users, numbers of prescriptions, frequencies of disorders/diseases, and specialties of the prescribing physicians were examined. The share of off-label prescriptions was calculated for each year. The prescription prevalence of antidepressants ranged between 1.7 and 2.1 per 1000 minors. The use of tricyclic antidepressants decreased from 0.9 to 0.6 prescriptions per 1000 minors, while the use of selective serotonin reuptake inhibitors increased from 0.5 to 1.1. Of the patients with an antidepressant prescription, 46.4% only received one prescription. Depression was by far the most frequent diagnosis among all antidepressant users as well as among subjects with only one prescription. In 2011, 36.3% of all prescriptions were off-label. The high proportion of single prescriptions, even in patients with a diagnosed depression, and the high rate of off-label use are particularly noteworthy and should be further investigated in future studies. Copyright © 2016 John Wiley & Sons, Ltd.

Pharmacotherapy in Psychiatric Disorders of Children: Current Evidence and Trends.

Pharmacotherapeutic interventions are available for most psychiatric disorders in children. Evidence for these interventions varies, depending on the targeted disorders. For attention-deficit/hyperactivity disorder, a sound database on efficacy and safety of medication exists. For other common disorders or psychopathological phenomena like disruptive behavior, anxiety disorders, depressive disorders, or autism, data on efficacy and safety are much scarcer. This selective review aims to provide an overview about current psychopharmacological interventions in child and adolescent psychiatry. The literature indicates either a lower efficacy than other interventions or less beneficial effects compared to possible adverse events in these cases. Most guidelines recommend psychopharmacotherapy in children to be embedded in a psychosocial or therapeutic intervention plan. Decision for medication depends on the severity of symptoms, chronicity, and, most important, impairment of the child in academic performance, family relationships, and everyday life. The high rates of off-label use in the age group of children are often due to a lack of market authorization studies less indicative of low efficacy. As adverse events need to be monitored closely, pharmacotherapy should mainly be restricted to experienced mental health care providers.

Outpatient antipsychotic drug use in children and adolescents in Germany between 2004 and 2011.

Studies from different countries showed increasing use of antipsychotics in pediatric patients. However, these studies were methodologically limited and could not assess underlying diagnoses and off-label use sufficiently. This is the first study to examine antipsychotic prescriptions in a representative sample of minors over a long period, looking at changes regarding substances and drug classes, underlying diagnoses, and the rate of off-label use. Claims data of about two million pediatric subjects were used to calculate annual prevalences and incidence rates of antipsychotic prescriptions for the years 2004-2011. Analyses were stratified by sex, age, and drug type. Numbers of prescriptions, frequencies of diseases/disorders, the prescribing physicians' specialties, and the share of off-label prescriptions were examined. During the study period, the prevalence of antipsychotic prescriptions ranged between 2.0 and 2.6 per 1000 minors. Antipsychotic prescriptions in children younger than 6years decreased from 2.42 per 1000 subjects in 2004 to 0.48 in 2011. Among antipsychotic users, 47.0% had only one prescription and hyperkinetic disorder was, by far, the most frequent diagnosis. The annual share of off-label prescriptions varied between 61.0 and 69.5%. Antipsychotics were mainly prescribed to manage aggressive and impulsive behaviors in hyperkinetic disorder patients. This explains the high share of off-label prescriptions but raises concerns, since efficacy and safety of antipsychotics in this indication have not been sufficiently investigated. The decreasing antipsychotic use in younger children and the high proportion of antipsychotic users with one-time prescriptions are striking and should be further investigated in the future.

High rates of off-label use in antibiotic prescriptions in a context of dramatic resistance increase: a prospective study in a tertiary hospital

The use of antibiotics, as any other drug, is regulated by the terms of its marketing authorisation, notified in the Summary of Product Characteristics (SPC). If a prescription is not in accordance with the SPC, the physician prescribes off-label. There is very little literature regarding off-label use of antibiotics in adult healthcare facilities. A prospective monocentric study was conducted during 11 days from February to June 2015 in hospitalised patients from a tertiary teaching hospital with a high prevalence of multidrug-resistant organism colonisation to evaluate off-label use of antibiotics. Two independent experts assessed whether prescriptions complied with the latest guidelines in infectious diseases and whether off-label use of antibiotics was associated with an increased risk of adverse events. In total, 160 antibiotic prescriptions were analysed, of which 76 (47.5%) were off-label. Of the 76 off-label prescriptions, 50 (65.8%) were off-label regarding indications and 26 (34.2%) regarding doses. Nevertheless, 46/50 off-label indications (92.0%) and only 14/26 off-label doses (53.8%) were approved by experts, especially because of dose adjustment requirements. During follow-up, the rate of reported adverse events was not statistically different between patients with (n = 76) and without (n = 84) off-label prescriptions (P = 0.35). In a context of multidrug resistance and a lack of new drugs, high rates (47.5%) of antibiotic off-label use were observed in our hospital, but without an increased rate of adverse events. Moreover, 78.9% of off-label uses were in accordance with guidelines. Therefore, the SPC is not the warrant of an appropriate use of antibiotics.

Trends in Off-Label Use of Second-Generation Antipsychotics in the Medicare Population From 2006 to 2012.

The study evaluated trends in the off-label use of second-generation antipsychotics in the Medicare population, a practice that has been identified as lacking adequate supporting evidence for many indications. Medicare claims data from 2006 to 2012 were used to identify beneficiaries who filled at least one prescription for any second-generation antipsychotic. Any use that was not associated with a medical claim for an approved indication in a given year was classified as off-label use. Rates of off-label use and of diagnoses associated with off-label use were compared over time. Fill counts standardized for 30-day supply and costs were compared by type of use. On the basis of a sample of 490,314 patient-years, the rate of off-label use among beneficiaries prescribed a second-generation antipsychotic declined from 51% to 45%. Fill counts were 16% lower for off-label users compared with on-label users. Off-label users had higher out-of-pocket costs but lower total costs for second-generation antipsychotics. Off-label users most commonly had claims related to dementia, minor depression, anxiety disorders, and other psychosis. The proportion of off-label users without any claims for the most common off-label uses of second-generation antipsychotics declined from 45% in 2006 to 30% in 2012. Off-label use of second-generation antipsychotics has declined, especially among persons without any of the common off-label conditions. The diagnoses accompanying off-label use did not systematically reflect changes in the evidence base for the use of these drugs, suggesting a mismatch between evidence supporting the use of off-label second-generation antipsychotics and prescribing practices.

Off-label prescribing of antiepileptic drugs in pharmacoresistant epilepsy: a cross-sectional drug utilization study of tertiary care centers in Italy.

To assess the extent of off-label prescribing of antiepileptic drugs (AEDs) and associated variables in a large population of patients with pharmacoresistant epilepsy. Descriptive analysis of data recorded from consecutively enrolled patients with pharmacoresistant epilepsy attending 11 tertiary referral centers in Italy. Off-label use was stratified by therapeutic indication, dose, and age. Multivariate logistic regression was used to identify variables associated with off-label prescription. Of a total of 1,124 patients enrolled between November 2006 and August 2007, 53 % (101/191) of children and 31 % (287/933) of adults were receiving at least one off-label AED prescription. Among adults, off-label use was related primarily to indication and was highest for clobazam (100 %) and ethosuximide (40 %), followed by lamotrigine (25 %), and vigabatrin (25 %). In children, clobazam (100 %), lamotrigine (79 %), vigabatrin (55 %), ethosuximide (46 %), and levetiracetam (43 %) were most frequently used off-label, with indication or age being the main causes depending on the specific AED. Logistic regression analysis indicated that higher rates of off-label use were associated with a polytherapy regimen (odds ratio [OR] 2.50, 95 % confidence interval [95 % CI], 1.55-4.03), pediatric age (2.49, 1.66-3.76), having failed ≥3 AEDs (2.16, 1.04-4.48), a diagnosis of generalized epilepsy with structural/metabolic or unknown etiology (2.97, 1.25-7.04), and increasing seizure frequency (1.07, 1.01-1.14). Off-label prescribing of AEDs is common among patients with pharmacoresistant epilepsy and is influenced by demographic and disease-related characteristics. Studies are needed to improve the quality of evidence guiding epilepsy treatment, and to evaluate the risks and benefits of off-label prescribing in epilepsy.

Off-label medicine use in pediatric inpatients: a prospective observational study at a tertiary care hospital in India.

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.

A Survey of Hepatitis C Treatment Clinical Practice Patterns Using the Newly Approved Protease Inhibitors

To describe current hepatitis C virus (HCV) treatment practices in the United States and identify physician characteristics associated with the use of first generation direct-acting antivirals (DAAs). HCV treatment practice patterns have not been assessed after the introduction of DAA, which are now considered standard of care for most HCV genotype 1 patients. We sampled nationally representative physicians treating HCV patients with DAAs through a web-based survey. Stepwise multivariate logistic regression was performed to identify physician characteristics associated with the use of DAAs in 4 clinical vignettes (early stage fibrosis, prior null response, human immunodeficiency virus (HIV) co-infection, and post-liver transplantation). Of 1658 deliverable emails, 337 (20.3%) clinicians responded. Fifty percent of providers recommended DAA therapy for treatment-naive patients with early stage fibrosis, whereas 49% of providers would await new therapies. For prior null responders with significant fibrosis, 74% would attempt retreatment using DAAs and 26% would await new therapies. Off-label use of DAAs was recommended by 69% of providers for patients with HIV infection and 48% of providers for post-liver transplant patients. Academic affiliation was significantly associated with higher rates of off-label use in both HIV and post-liver transplant patients. Despite more potent and less toxic therapies on the horizon, many physicians recommended DAAs in treatment-naive patients with early stage fibrosis. Providers also frequently recommended DAAs for off-label uses, such as treating post-liver transplant patients and those coinfected with HIV.

Off-Label Use of Pharmaceuticals: Trends and Drivers

We identify the rate of off-label use of prescription drugs in the United States during 1993-2008. We apply Detection Controlled Estimation to a comprehensive cross-section of prescriptions and find that rates of off-label use rise from 30.2% to 39.1% during this period. This coincides with a surge in settlements of Department of Justice lawsuits for off-label marketing. Additionally, physicians are more likely to prescribe off-label when there are fewer FDA-approved alternatives and when a patient’s insurance has less restrictive formularies and lower copayments. These substitution patterns are consistent with off-label prescribing by physicians that enhances the welfare of patients.