Risk Of Off-label Use Research Articles

Assessing National Trends and Perceived Safety of Off-Label Ciprofloxacin-Dexamethasone Use by Pediatric Otolaryngologists.

Off-label use of Ciprodex® (ciprofloxacin-dexamethasone: CPD), an antibiotic-steroid combination solution, in the airway has been reported by pediatric otolaryngologists with anecdotal success. We examined national trends regarding off-label CPD use including prevalence, common indications, prescriber patterns, adverse events, and accessibility. 15-item cross-sectional survey was distributed to American Society of Pediatric Otolaryngology members from January-April 2022. Univariate analyses were performed to compare responses for users of off-label CPD versus non-users. Ease of access was compared across geographies and practice types using multivariate logistic regressions. Of the 163 complete responses (26.6% response rate), 156 (95.7%) reported using off-label CPD. Most common indications for off-label CPD were tracheal granulation (87.8%, n = 137) and choanal atresia (82.1%, n = 128). Ease of access was significantly increased in the Midwest (OR:18.79, 95%CI:3.63-1.24, p = 0.001) and West (OR:29.92, 95%CI:3.55-682.00, p = 0.006). Ease of access was significantly lower at tertiary referral centers (OR:0.11, 95%CI:0.01-0.64, p = 0.041) and private practices (OR:0.04, 95%CI:0.002-0.33, p = 0.009) compared to academic free-standing children's hospitals. Two-thirds of respondents reported feeling "Very Comfortable" with the safety profile of off-label CPD; 99.4% (n = 156) felt that the benefits outweighed the risks of off-label use. Seven respondents (4.5%) reported adverse events (e.g., local allergic reaction, cushingoid symptoms) from off-label use. Our findings (26.6% response rate) suggest that off-label CPD is commonly used by pediatric otolaryngologists, many of whom reported feeling that the benefits of off-label CPD outweigh the risks. Our results establish a baseline for future efforts to assess the efficacy and safety of off-label CPD and to improve its accessibility. V Laryngoscope, 134:2922-2930, 2024.

Off-Label Use vs Off-Label Marketing of Drugs: Part 1: Off-Label Use—Patient Harms and Prescriber Responsibilities

Once medical drugs and devices are approved for marketing by the FDA they can legally be used for purposes and in ways other than the ones for which they have been tested and approved. However, it is illegal for manufacturers to advertise or promote such unapproved uses of the drugs and devices. Part 1 of this review focuses on off-label use of FDA-approved therapies. Part 2 addresses illegal off-label marketing of drugs and devices. While off-label use can be beneficial to patients, unless carefully undertaken off label use may undermine the important safety mission of the FDA, can expose patients to elevated risks without proven benefits (or possibly no benefit), and can reduce motivation of companies to study the safety and risks of off-label use of therapies. These problems are further amplified when off-label use occurs among very vulnerable patient populations such as the elderly, patients with mental health disorders, pregnant women and pediatric patients. This review considers ethical issues in off-label use, as well as important steps for physicians considering an off-label prescription of a drug or device.

Prevalência do uso de ivermectina para prevenir COVID-19 durante a pandemia em Mato Grosso: estudo transversal de base domiciliar

To analyze the use of ivermectin as COVID-19 prevention method by the population of Mato Grosso in 2020. This is a home-based survey, carried out between September and October 2020, in 10 pole cities of the socioeconomic regions of State. The use of ivermectin was evaluated through the question: "Did you take ivermectin to prevent COVID-19?". Sociodemographic variables (sex, age group, education, family income), current work situation, being benefitted by government financial programs, as well as symptoms, seroprevalence of antibodies against SARS-CoV-2, and previous diagnosis of COVID-19 were evaluated. Prevalence and their associations were estimated using the chi-square test. 4.206 individuals were evaluated for prevalence of ivermectin use; 58.3% of the individuals responded positively, this rate being higher in the municipalities of the western region of the state (66.6%). There was no significant difference between sexes, but the prevalence was higher among people aged 50-59 years (69.7%), who were white (66.5%), with complete higher education or more (68.8%) and higher family income (≥3 minimum wages-64.2%). The use of this drug was even higher among participants who considered their knowledge of the disease good or very good (65.0%), who reported having symptoms of COVID-19 (75.3%), and who had been previously diagnosed with the disease (91.2%). There was a high prevalence of use of ivermectin as a method to prevent covid-19 by the population of Mato Grosso, indicating the need for strategies to inform the population about the risks of off-label use of drugs and to combat the advertising of drugs that are ineffective against COVID-19.

Patient-perceived benefits and risks of off-label use of SGLT2 inhibitors and GLP-1 receptor agonists in type 1 diabetes: a structured qualitative assessment.

Patients with type 1 diabetes mellitus (T1DM) may have suboptimal glucose control and are interested in the use of adjuvant therapies. To determine, from the patients' perspective, the reasons for initiation of glucagon-like peptide 1 receptor agonist (GLP-1RA) and/or sodium glucose cotransporter 2 inhibitor (SGLT2i) in treating T1DM; perceived benefits/side effects, reasons for discontinuation, and willingness to reinitiate therapy. Retrospective chart review with structured telephone interviews. We identified patients with T1DM treated with a GLP-1RA and/or SGLT2i for >3 months at University of Texas Southwestern Medical Center (Dallas, TX, USA) and Poznan University (Poznan, Poland). We conducted structured telephone interviews regarding their experiences. We interviewed 68 participants treated with GLP-1RA and 82 with SGLT2i. Treatment was initiated for improving glycemic control (as reported by 61.8% versus 81.7% of GLP-1RA and SGLT2i users, respectively), weight loss/appetite suppression (51.4% versus 23.2%) and to reduce insulin requirement (13.2% versus 11%). Most participants (86.8% of GLP-1RA and 89.0% of SGLT2i users) reported ⩾1 benefit attributed to therapy. Reported benefits were improved glycemic control (reported by 58.8% versus 82.9% of GLP-1RA and SGLT2i users, respectively), weight loss/appetite suppression (63.2% versus 30.5%), and reduced insulin requirement (27.9% versus 34.1%). More GLP-1RA users reported side effects versus SGLT2i users (63.2% versus 36.6%); 22.6% discontinued GLP-1RA due to side effects versus 11.0% SGLT2i users. Diabetic ketoacidosis (DKA) was reported by 4.9% of SGLT2i users, but none in GLP-1RA users. Of those who discontinued medication, 60.7% of GLP-1RA versus 56.0% of SGLT2i prior users were willing to reinitiate treatment. Patients with T1DM report initiating adjuvant treatment with GLP-1RA and/or SGLT2i to improve glycemic control and lose weight; most patients reported perceived benefits from these therapies. Side effects (including DKA) are reported more commonly in real life than in clinical trials. Given patient interest in these medications, further studies should evaluate the long-term risk-benefits ratio in larger cohorts.

Benefits and risks of off label use of antipsychotics in insomnia and anxiety – APSY Oulu project

Background Use of antipsychotics (APs) has increased in Europe. Main reason for this is off label use, most commonly the use of quetiapine for insomnia and anxiety. However, there is lack of studies analysing benefits and harms of APs in these conditions. APs have shown efficacy in the treatment of anxiety, but long term follow-ups are rare. Only two trials on effects of quetiapine in primary insomnia exist. Even small doses of APs may cause side-effects, such as increased weight, metabolic changes, and daytime drowsiness, but studies on small dose of APs are very few. The aim of the APSY Oulu project (https://www.oulu.fi/ltk/apsyoulu) is to study the benefits and risks of APs in off label use. Methods APSY Oulu project includes clinical patient data, questionnaire on physicians on APs off label prescriptions and systematic literature reviews on the topic. Results In 2019–2020, we have collected pilot sample of 10 individuals starting quetiapine for insomnia, followed up for 12 months. They all had severe or very severe symptoms of insomnia, and used very small dose of quetiapine (mostly 12.5–25 mg). Four of them used quetiapine still at the 12 months follow-up, and their insomnia symptoms decreased during the follow-up. Side effects were common (e.g. increase heart rate, drowsiness). Based on questionnaire for Finnish physicians, APs off label prescriptions are mostly for insomnia and anxiety, most common drug being quetiapine. There is a need for guideline on monitoring the patients. Conclusions Further studies on APs off label use and its safety are needed.

Benefit-Risk Assessment of Off-Label Drug Use in Children: The Bravo Framework.

A drug is granted a license for use after a thorough assessment of risks and benefits based on high‐quality scientific proof of its efficacy and safety. Many drugs that are relevant to children are not licensed for use in this population implying that a thorough assessment of risks and benefits in the pediatric population has not been made at all, implying a negative risk‐benefit balance in children, or implying insufficient information to establish the risk‐benefit balance. Use of drugs without positive assessment of risks and benefits exposes children to potential lack of efficacy, unknown toxicity, and harm. To aid guideline committees and individual prescribers, we here present a tutorial of the Benefit and Risk Assessment for Off‐label use (BRAvO) decision framework. This pragmatic framework offers a structured assessment of benefits and risks of off‐label drug use, including a clinical pharmacological based approach to age‐appropriate dose selection. As proof of concept and to illustrate the practical use, we have applied the framework to assess benefits and risks of off‐label use of ondansetron for gastroenteritis‐induced nausea and vomiting. The framework could also guide decisions on off‐label use in other special populations (e.g., pregnant women, elderly, obese, or critically ill patients) where off‐label drug use is frequent, thereby contributing to effective and safe pharmacotherapy.

THE OFF- LABEL USE OF CARBAMAZEPINE IN INDONESIA

Objective:. In Indonesia, carbamazepine was approved by The National Agency of Drugs And Foods Controls for the prophylaxis of lithium unresponsive manic-depressive disorders, all types of epilepsy (except for petit mal), and trigeminal neuralgia. This study was conducted to determine the off-label use of carbamazepine in Indonesia.Methods: This research is a nonexperimental descriptive study with a cross-sectional method. Data collection retrospectively by taking all patients that were prescribed carbamazepine in 2014. Data were obtained from four general hospitals in Yogyakarta. The off-label use of carbamazepine was defined a prescribing of carbamazepine outside the indication that approved by The National Agency for Drugs And Foods Controls of Republic of Indonesia (NA-DFC).Results: The use of carbamazepine in 2014 were 704 prescriptions, and on 251 (35.6%) of them were off-label drug use. The off-label use of carbamazepine were 149 prescriptions (59.4%) for neuropathic pain, 83 prescriptions (33.0%) for nociceptive pain, and 19 prescriptions (7.6%) for other indications.Conclusion: The mostly off-label use of carbamazepine in Indonesia was in neuropathic pain with low evidence. Further research to study the efficacy and the risk of off-label use of carbamazepine may be an essential step toward defining the potential for such purpose.

Off-Label Use in Rare Diseases: Myasthenia Gravis, Lambert-Eaton Myasthenic Syndrome and Congenital Myasthenic Syndromes

AbstractThe off-label use of licensed drugs is widespread, and the risk of adverse events is elevated, especially if the scientific evidence is low. The treatment of rare diseases (<5/10,000) therefore may increase the risk of off-label use. The optimized standard treatment is primarily based on the regulatory decisions of the German Federal Joint Committee. The valid guidelines and the regulations of the German health system are discussed in this article. The criteria for indication and monitoring of off-label use are shown, especially focused on the problem of refractory myasthenia gravis. Escalation of treatment results regularly in off-label use. The arguments within the applicable guidelines should be followed. Some new aspects of the European regulations are likewise discussed.

Value-based and benefit-based strategies in deciding to bring a test into use should be distinguished

BackgroundRegulatory and health technology assessment agencies have commented differently on the question whether results from enrichment studies can be used to justify to bring a test into use. We try to provide a framework to discuss this issue.ResultsMathematical definitions for the value and the benefit of a new diagnostic test are given. The possible conclusions about value and benefit from enrichment studies and interaction studies are explored. The terms benefit-based strategy and value-based strategy are introduced. Several potential consequences of using one of the two strategies in deciding to bring a test into use are identified and quantified. Interaction designs allow to assess benefit and value. Enrichment designs allow only to assess benefit. However, it is often probable that interaction studies allow no firm conclusions about the value. The advantage of a benefit-based strategy stems mainly from allowing test-positive patients earlier or even ever to benefit. The main disadvantage is a potential delay in detecting tests of no value.ConclusionsBenefit-based strategies are preferable if the risk of off-label use and of delayed decisions on the value of a test can be limited. Otherwise, the superiority depends highly on research practice.

Summary of the comparative effectiveness review on off-label use of atypical antipsychotics.

BACKGROUND: Conventional and atypical antipsychotic medications are approved by the FDA for treatment of schizophrenia and bipolar disorder. Over many decades, the widespread use of conventional antipsychotics produced various side effects requiring additional medications, such as the atypical antipsychotics. Beginning in 2006, 9 atypical antipsychotic drugs have been approved by the FDA for indications that were previously off-label uses: aripiprazole (as augmentation for major depressive disorder [MDD] and for autism spectrum disorders ), asenapine, clozapine, iloperidone, olanzapine (in combination with fluoxetine for MDD and bipolar depression), paliperidone, quetiapine (quetiapine and quetiapine XR [extended release] as monotherapy in bipolar depression and quetiapine XR as augmentation for MDD), risperidone (for autism spectrum disorders), and ziprasidone. In 2006, the Agency for Healthcare Research and Quality (AHRQ) published a systematic review on the comparative effectiveness of off-label uses o...

Off-Label Pharmacovigilance

This edition of Drug Safety contains the abstracts for the annual International Society of Pharmacovigilance (ISoP) meeting being held in Istanbul, Turkey, 26–28 October 2011. Browsing the agenda for the meeting indicates that a session will be devoted to off-label use of drugs. This interesting topic has not been pursued much in pharmacovigilance, but it should be in the core of what we do. In a recent editorial in Nature Medicine, the risk of off-label use was exemplified by haemostatic agent recombinant factor VIIa (rFVIIa; also known as eptacog alfa) [NovoSeven , Novo-Nordisk]. They referred to a postmarketing review of 35 studies showing increased risk of arterial thromboembolic events in patients with various clinical conditions, but not in healthy volunteers, treated with NovoSeven through off-label use as well as some other studies. Another review of rFVIIa concludes by saying ‘‘... The outcomes (effectiveness and safety) of all off-label uses should be systematically evaluated and reported. Adequate data to assess cost effectiveness for eptacog alfa does not exist for most off-label indications.’’ The Nature Medicine review also points to an increase in off-label use of drugs in other therapeutic areas. The US FDA has recently added a ‘black-box’ warning to NovoSeven ’s label of serious thrombotic adverse events linked to off-label use. These postmarketing findings have clear safety implications and the first, and obvious, message is that safety in conditions other than haemophilia could only have been signalled if the indication for using the drug was known. Individual case harm reports (ICHRs) often do not mention indication for use; moreover, during investigation of healthcare databases, I have found that it is not always clear what the indication for the use of a drug really is, and sometimes the labelled indication ismentionedwhen it does not seem correct for the clinical setting. If we are to find early signals of this sort we must redouble our efforts to get full and accurate information both in ICHRs and also recorded in healthcare databases. Proven data quality is arguably a more pressing issue than ‘underreporting’. The circumstances of off-label use of drugs certainly must be fully documented for there to be a chance of considering benefit or effectiveness to risk balance for the individuals treated. Some years agoKees vanGrootheest andmyself pointed out some approaches to tackle off-label prescribing. In summary these were as follows: 1. Education: Clinicians need to know about the comparative merits of the effectiveness and risk of drugs, as well as how they work pharmacologically and toxicologically, and what interactions they have with each other. 2. Frequently, physicians do not consult the Summary of Product Characteristics (SPC) for verification, leaving aside whether they have taken notice of the contents of the official SPC in the first place. We recommended that the accessibility of SPCs should be enhanced for doctors and pharmacists, drawing attention specifically to any changes. There needs to be a single body of information that covers every drug. 3. Communication and understanding: There is much to be done in this area both in terms of follow-up and understanding of health professionals’ behaviour and how to empower best practice. The dispensing pharmacist can play an important role in the implementation of warnings and contraindications. 4. Professional freedom: It goes without saying that doctors who issue off-label prescriptions EDITORIAL Drug Saf 2011; 34 (10): 795-797 0114-5916/11/0010-0795/$49.95/0

Use of recombinant factor VIIa for the prevention and treatment of bleeding in patients without hemophilia: a systematic review and meta-analysis.

The benefits and risks of off-label use of recombinant factor VIIa in patients without hemophilia are contested. We performed a systematic review to assess the effectiveness and safety of such use. We searched electronic databases including MEDLINE, EMBASE and CENTRAL for randomized controlled trials comparing recombinant factor VIIa with placebo in any patient population except those with hemophilia up to January 2010. Eligible articles were assessed for inclusion, data were extracted, and study quality was evaluated. Outcomes included mortality, blood loss, requirements for red blood cell transfusion, number of patients transfused and thromboembolic events. We identified 26 trials: 14 on off-label prophylactic use of recombinant factor VIIa (n = 1137) and 12 on off-label therapeutic use (n = 2538). In the studies on prophylactic use, we found no significant difference in mortality or thromboembolic events between the treatment and placebo groups. We found modest benefits favouring recombinant factor VIIa in blood loss (weighted mean difference -276 mL, 95% confidence interval [CI] -411 to -141 mL), red blood cell transfusion (weighted mean difference -281 mL, 95% CI -433 to -129 mL) and number of patients transfused (relative risk 0.71, 95% CI 0.50 to 0.99). In the therapeutic trials, we found a nonsignificant decrease in mortality and a nonsignificant increase in thromboembolic events but no difference in control of bleeding or red blood cell transfusion. Clinically significant benefits of recombinant factor VIIa as a general hemostatic agent in patients without hemophilia remain unproven. Given its potential risks, such use cannot be recommended, and in most cases, it should be restricted to clinical trials.

Guidance for off-label use of drugs

Guidance for off-label use of drugs

Contrast Media and Mechanical Power Injection

Over 10 million radiological exams requiring intravenous (IV) injection of contrast media are performed in the United States each year, and the number is growing. Iodinated contrast media are commonly used to assess venous patency, assist in vascular access, and determine access device position and function. The majority of these procedures are completed without incident; however, IV injection of contrast media is not without risk. Power injection of contrast may accelerate or amplify some adverse effects. The American College of Radiology has published standards and guidelines for intravenous injection of contrast media. Poiseuille's law of laminar flow was addressed as an important concept in understanding the fluid mechanics involved in contrast media injection. The benefits and potential risks of mechanical power injectors were presented. Published studies of power injection through central venous access devices were summarized and discussed, including risks of off label use.