[Clinical management of treatment-resistant depression]. / Klinisches Management der therapieresistenten Depression.

Treatment-resistant depression (TRD) is a complex disorder. Although no standardized definition has been established to date, there are promising and well-established treatment options for the condition. Looking at the current pharmacological and neuromodulatory strategies, there is an urgent need for fast-acting and well-tolerated treatment options. The search for new mechanisms of action goes beyond the monoamine hypothesis. For example, esketamine is already an established treatment method that is fast-acting and well tolerated, while psychedelics or esmethadone are currently still undergoing clinical trials. Compounds that can be used off-label, such as dextromethorphan or anti-inflammatory strategies are also presented. Pharmacological approaches that focus on the modulation of the glutamatergic system or belong to the class of psychedelics, appear to be of particular importance for current research and development. These particularly include substances that rapidly exert clinical effects and have a favorable side-effect profile.

Diagnosis and Treatment of ADHD in the Pediatric Population.

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in childhood with approximately 6 million children (age 3 to 17 years) ever diagnosed based on data from 2016-2019. ADHD is characterized by a constant pattern of inattention and/or hyperactivity-impulsivity symptoms that interferes with development or functioning. Specific criteria from the Diagnostic and Statistical Manual of Mental Disorders, 5th edition Text Revision assist with the diagnosis with multiple guidelines available providing non-pharmacologic and pharmacologic recommendations for the treatment of ADHD in the pediatric population. While all guidelines similarly recommend behavioral and/or stimulant therapy as first-line therapy based on age, not all stimulant products are equal. Their differing pharmacokinetic profiles and formulations are essential to understand in order to optimize efficacy and safety for patients. Additionally, new stimulant products and non-stimulant medications continue to be approved for use of ADHD in the pediatric population and it is important to know their differences in formulation, efficacy, and safety to other products currently available. Lastly, due to drug shortages, it is important to understand product similarities and differences to select alternative therapy for patients.

Letermovir prophylaxis for cytomegalovirus in lung-transplant recipients: a comprehensive study with literature review of off-label use and real-world experiences.

Letermovir, initially approved for cytomegalovirus (CMV) prophylaxis in hematopoietic stem-cell transplantation, has gained attention for off-label use in lung-transplant (LTx) recipients. Given the high susceptibility of LTx recipients to CMV infection, this study explores the effectiveness and safety of letermovir prophylaxis. A retrospective analysis of using letermovir for LTx recipients at Tohoku University Hospital (January 2000 to November 2023) was conducted. Case summaries from other Japanese transplant centers and a literature review were included. Six cases at Tohoku University Hospital and one at Kyoto University Hospital were identified. Prophylactic letermovir use showed positive outcomes in managing myelosuppression and preventing CMV replication. The literature review supported the safety of letermovir in high-risk LTx recipients. Despite limited reports, our findings suggest letermovir's potential as prophylaxis for LTx recipients intolerant to valganciclovir. Safety, especially in managing myelosuppression, positions letermovir as a promising option. However, careful consideration is important in judiciously integrating letermovir into the treatment protocol.

Barriers and facilitators to guideline for the management of pediatric off-label use of drugs in China: a qualitative descriptive study.

BACKGROUND: Despite being a global public health concern, there is a research gap in analyzing implementation strategies for managing off-label drug use in children. This study aims to understand professional health managers' perspectives on implementing the Guideline in hospitals and determine the Guideline's implementation facilitators and barriers. METHODS: Pediatric directors, pharmacy directors, and medical department directors from secondary and tertiary hospitals across the country were recruited for online interviews. The interviews were performed between June 27 and August 25, 2022. The Consolidated Framework for Implementation Research (CFIR) was adopted for data collection, data analysis, and findings interpretation to implement interventions across healthcare settings. RESULTS: Individual interviews were conducted with 28 healthcare professionals from all over the Chinese mainland. Key stakeholders in implementing the Guideline for the Management of Pediatric Off-Label Use of Drugs in China (2021) were interviewed to identify 57 influencing factors, including 27 facilitators, 29 barriers, and one neutral factor, based on the CFIR framework. The study revealed the complexity of the factors influencing managing children's off-label medication use. A lack of policy incentives was the key obstacle in external settings. The communication barrier between pharmacists and physicians was the most critical internal barrier. CONCLUSION: To our knowledge, this study significantly reduces the implementation gap in managing children's off-label drug use. We provided a reference for the standardized management of children's off-label use of drugs.

[Ophthalmic agents during pregnancy]. / Ophthalmika in der Schwangerschaft.

The use of ophthalmic agents during pregnancy and breastfeeding always represents an off-label use. Therefore, the use of drugs must be particularly carefully assessed with respect to the risk-benefit assessment. In this overview the literature databank of the PubMed library, pharmaceutical lists (Red List, Swiss pharmaceutical compendium), guidelines of the specialist societies the German Society of Ophthalmology (DOG), the Swiss Society of Ophthalmology (SOG), the European Glaucoma Society (EGS), the American Academy of Ophthalmology (AAO) and internet portals (embryotox, reprotox) were inspected and recommendations for the use of ophthalmic agents during pregnancy and breastfeeding were derived. More attention should be dedicated to this topic in the specialist societies.

Right-sided vagus nerve stimulation for drug-resistant epilepsy: A systematic review of the literature and perspectives.

BACKGROUND: Right-sided vagus nerve stimulation (RS-VNS) is indicated when the procedure was deemed not technically feasible or too risky on the indicated left side. OBJECTIVE: The present study aims to systematically review the literature on RS-VNS, assessing its effectiveness and safety. METHODS: A systematic review following PRISMA guidelines was conducted: Pubmed/MEDLINE, The Cochrane Library, Scopus, Embase and Web of science databases were searched from inception to August 13th,2023. Gray literature was searched in two libraries. Eligible studies included all studies reporting, at least, one single case of RS-VNS in patients for the treatment of drug-resistant epilepsy. RESULTS: Out of 2333 initial results, 415 studies were screened by abstract. Only four were included in the final analysis comprising seven patients with RS-VNS for a drug-resistant epilepsy. One patient experienced nocturnal asymptomatic bradycardia whereas the other six patients did not display any cardiac symptom. RS-VNS was discontinued in one case due to exercise-induced airway disease exacerbation. Decrease of epileptic seizure frequency after RS-VNS ranged from 25 % to 100 % in six cases. In the remaining case, VNS effectiveness was unclear. In one case, RS-VNS was more efficient than left-sided VNS (69 % vs 50 %, respectively) whereas in another case, RS-VNS was less efficient (50 % vs 95 %, respectively). CONCLUSION: Literature on the present topic is limited. In six out of seven patients, RS-VNS for drug-resistant epilepsy displayed reasonable effectiveness with a low complication rate. Further research, including prospective studies, is necessary to assess safety and effectiveness of RS-VNS for drug-resistant epilepsy patients.

[Translated article] Current situation and evolution of the availability of drugs in the pediatric population in Spain.

OBJECTIVE: To analyze the characteristics of the new medicines approved in the pediatric population in the last 3 years, both those with studies only in the pediatric population and those that extend their indication in this population group, as well as the current situation in relation to their marketing and financing. METHODS: Descriptive observational study of all drugs that include an indication in the pediatric population in Spain (by extension of the indications of drugs already authorized or because they are new drugs that already include an indication in this population group), from January 2019 to March 2022. RESULTS: During the study period, 129 drugs included their indication in the pediatric population. 13.9% of them are not marketed, 46.5% are in a situation of non-financing, under study or without a request for financing, and 4.6% are financed for a specific pediatric subpopulation. 52.7% are original drugs, 4.7% are generic, 38.8% are biological, 3.8% are biosimilar, and 17.8% are orphan drugs. 57.36% of these medicines obtain the pediatric indication due to extension of the indication and 42.64% obtain it because they are new medicines that already include their studies in the pediatric population. CONCLUSIONS: Drugs with authorized indications are increasingly available in the pediatric population and the trend is to extend the indication of authorized drugs to the adult population. However, barriers in terms of financing and marketing need to be expedite and overcome to facilitate access to them.

On- and Off-Label Atypical Antipsychotic Prescription Trends Across a Nine-Year Period Among Adolescents Pre- to Post-COVID-19.

OBJECTIVE: This study examined atypical antipsychotic prescribing by Food and Drug Administration (FDA) approved-use (on-label) status for adolescents before and during the COVID-19 pandemic. METHODS: Retrospective data were collected from electronic health records (EHRs) of adolescents aged 10-17 years in Kaiser Permanente Northern California. New outpatient atypical antipsychotic prescription orders during 2013-2021 were evaluated. Prescriptions were categorized as on-label if linked in EHRs to autism, psychosis, bipolar disorder, or Tourette's diagnoses; otherwise, they were potentially off-label (herein, off-label). Trend analysis of monthly prescribing rates assessed slope change at pandemic onset for the cohort and by sex and age groups. RESULTS: Among 5828 patients, 74.5% of new antipsychotic orders were off-label in 2021. Overall prescribing decreased significantly until early 2020 (slope = -0.045, P < .01) but then significantly increased through 2021 (post-March 2020 slope change = 0.211, P = .01). Off-label prescriptions increased at a similar rate during the COVID-19 time period, but on-label prescriptions did not change significantly. Males and younger adolescents (ages 10-14 years) showed significant decreases until early 2020, while females and older adolescents (ages 15-17 years) did not. Females and younger adolescents exhibited significant increases in overall and off-label prescribing rates following pandemic onset; older adolescents exhibited increases in overall prescriptions while males had no detectable changes. CONCLUSIONS: Antipsychotic prescribing declined slightly but then increased significantly following COVID-19 onset for overall and off-label prescriptions. Pandemic onset differentially impacted antipsychotic prescribing by sex and age, with overall and off-label prescribing driven by increases among female and younger adolescents.

A Randomized Controlled Trial of Povidone-Iodine Versus Chlorhexidine Gluconate With Isopropyl Alcohol for Preoperative Vaginal Antisepsis.

Many surgeons request use of 10% povidone-iodine (PI) for vaginal antisepsis; however, when PI is contraindicated, some surgeons request use of chlorhexidine gluconate (CHG) instead. The purpose of this randomized controlled trial was to determine any significant differences in self-reported symptoms associated with vaginal antisepsis with either 10% PI scrub or 4% CHG with 4% isopropyl alcohol. The control group comprised 62 participants who underwent vaginal antisepsis with the PI product, and the intervention group comprised 58 participants who underwent vaginal antisepsis with the CHG product. Participants completed surveys immediately before surgery, immediately after surgery, and 48 to 72 hours after surgery. No significant differences were found in the reported vaginal symptoms between the two groups for any survey. One participant in the intervention group reported symptoms consistent with an allergic reaction. Additional studies are needed on the use of CHG for vaginal antisepsis.

Model-based exploration of the rationality of off-label use of cetirizine in Chinese pediatric patients: a prospective cohort study.

Aims: Cetirizine is frequently administered at an increased dosage in clinical practice and recommended by several guidelines. Nonetheless, the pharmacokinetic (PK) profile and real-world safety data remain insufficient in the Chinese pediatric population. The objective of the current study is to develop a population pharmacokinetic (PPK) model for cetirizine in Chinese pediatric patients and to investigate the rationale behind its off-label usage. Methods: A prospective cohort study was conducted, enrolling children who had been diagnosed with allergic diseases and prescribed cetirizine. The outcomes were safety and pharmacokinetic (PK) parameters. Cetirizine concentrations were measured using a pre-established analytical method. Subsequently, a PK model was developed, followed by model evaluation and simulation. The developed PK model was employed to investigate the drug exposure differences across various age groups and to simulate scenarios of potential overdose. Results: Sixty-three children were enrolled, and 24 of them received a cetirizine dose exceeding the recommended dosage. A PPK model, based on published literature, served as the basis of our analysis, with adjustment made to estimate certain parameters. The final model evaluation and validation indicated accurate predictive performance and robust parameter estimation. Simulations conducted for the label-dose among age 1-12 indicated median maximum concentration at steady state (Cmax,ss) of 7 year old children could be the highest. The model was also used to predict the off-label dose scenarios and overdose patient to support the clinical decision. There were no adverse drug reactions in either group. Conclusion: This study provides evidence-based and model-based exploration for optimizing cetirizine usage in Chinese pediatric patients. The cetirizine PPK model showed accurate predictive performance and could be utilized to simulate individual patient exposure in real-world clinical scenarios.

Use of antimicrobials in pediatric wards of five Brazilian hospitals.

The use of antimicrobials (AMs) in pediatric infections is common practice and use may be inappropriate leading to antimicrobial resistance. Off-label AM use is also common in this group and can result in drug-related problems. There is lack of DUR data in Brazil and in Latin America, specially for AM pediatric use. The aim of this study was to describe the utilization of AMs in hospitalized children in five hospitals in Brazil. We conducted an observational study of the utilization of AMs in pediatric wards in hospitals in the states of Ceará (CE), Sergipe (SE), Rio de Janeiro (RJ), Rio Grande do Sul (RS) and the Federal District (DF). Data derived from patient medical records and prescriptions were collected over a six-month period in each hospital. The number of AMs used by each patient was recorded, and AM use was assessed using Days of therapy (DOT) and Length of therapy (LOT) per 1000 patient days according to different patient characteristics. Off-label (OL) use was described according to age. The study analyzed data from 1020 patients. The sex and age distributions were similar across the five hospitals. However, differences were found for comorbidities, history of ICU admission and length of hospital stay. The most common diseases were respiratory tract infections. There were wide variations in DOT/1000PD (278-517) and LOT/1000PD (265-390). AM utilization was highest in the hospital in SE. The consumption of second-generation penicillins and cephalosporins was high. The prevalence of OL use of AMs was higher for patients in the RJ hospital, in infants, in patients who underwent prolonged hospital stays, and in patients who used multiple AMs. The AM that showed the highest prevalence of OL use was azithromycin, in both oral and parenteral formulations. Overall AM use was high and showed differences in each setting, possibly influenced by local characteristics and by prescribing standards adopted by pediatricians.

Editor's Choice - Comparison of Open Surgery and Endovascular Techniques for Juxtarenal and Complex Neck Aortic Aneurysms: The UK COMPlex AneurySm Study (UK-COMPASS) - Peri-operative and Midterm Outcomes.

OBJECTIVE: Treatment of juxtarenal and complex neck abdominal aortic aneurysms (AAAs) is now commonly by endovascular rather than open surgical repair (OSR). Published comparisons show poor validity and scientific precision. UK-COMPASS is a comparative cohort study of endovascular treatments vs. OSR for patients with an AAA unsuitable for standard on label endovascular aneurysm repair (EVAR). METHODS: All procedures for AAA in England (November 2017 to October 2019) were identified, AAA anatomy assessed in a Corelab, peri-operative risk scores determined, and propensity scoring used to identify patients suitable for either endovascular treatment or OSR. Patients were stratified by aneurysm neck length (0 - 4 mm, 5 - 9 mm, or ≥ 10 mm) and operative risk; the highest quartile was considered high risk and the remainder standard risk. Death was the primary outcome measure. Endovascular treatments included fenestrated EVAR (FEVAR) and off label standard EVAR (± adjuncts). RESULTS: Among 8 994 patients, 2 757 had AAAs that were juxtarenal, short neck, or complex neck in morphology. Propensity score stratification and adjustment method comparisons included 1 916 patients. Widespread off label use of standard EVAR devices was noted (35.6% of patients). The adjusted peri-operative mortality rate was 2.9%, lower for EVAR (1.2%; p = .001) and FEVAR (2.2%; p = .001) than OSR (4.5%). In standard risk patients with a 0 - 4 mm neck, the mortality rate was 7.4% following OSR and 2.3% following FEVAR. Differences were smaller for patients with a neck length ≥ 5 mm: 2.1% OSR vs. 1.0% FEVAR. At 3.5 years of follow up, the overall mortality rate was 20.7% in the whole study population, higher following FEVAR (27.6%) and EVAR (25.2%) than after OSR (14.2%). However, in the 0 - 4 mm neck subgroup, overall survival remained equivalent. The aneurysm related mortality rate was equivalent between treatments, but re-intervention was more common after EVAR and FEVAR than OSR. CONCLUSION: FEVAR proves notably safer than OSR in the peri-operative period for juxtarenal aneurysms (0 - 4 mm neck length), with comparable midterm survival. For patients with short neck (5 - 9 mm) and complex neck (≥ 10 mm) AAAs, overall survival was worse in endovascularly treated patients compared with OSR despite relative peri-operative safety. This warrants further research and a re-appraisal of the current clinical application of endovascular strategies, particularly in patients with poor general survival outlook owing to comorbidity and age.

Identifying in-market application of Pelargonium root extract EPs 7630 for the treatment of COVID-19: analysis of pharmacovigilance data.

Introduction: Phytopharmaceutical products are successfully used for acute respiratory infections and may therefore be promising candidates for adjuvant symptomatic treatment of COVID-19. In vitro and clinical studies suggest that the proprietary Pelargonium sidoides DC. root extract EPs 7630 has antiviral and immunomodulatory properties, and effects on SARS-CoV-2 propagation have been shown in vitro. Medicinal products containing the extract have been approved for the symptomatic treatment of acute viral respiratory tract infections. Methods: We present a retrospective review of case reports submitted spontaneously to the pharmacovigilance database of the manufacturer of EPs 7630 and containing information on the off-label use of the extract for the treatment and prophylaxis of COVID-19 and of post-COVID-19 syndrome. Eligible case reports were identified by automated database searches. Results: Forty-four case reports filed between December 2019 and February 2023 were eligible for analysis. More than ¾ described the use of EPs 7630 for treatment of COVID-19 while the remaining reports referred to the treatment of post-COVID-19 syndrome or to COVID-19 prophylaxis. 15/22 cases which reported on treatment duration indicated an intake of EPs 7630 for up to 7 days. Five case reports indicated the use of EPs 7630 as COVID-19 monotherapy while 14 indicated a combination treatment with other drugs. All 28 cases that reported on treatment outcome characterized the patients as improved. Thirty case reports (68%) did not indicate any complications. The most frequent suspected adverse reactions were gastrointestinal complaints and hypersensitivity reactions, both of which may occur as known adverse effects of EPs 7630. No unexpected adverse reactions were observed. Conclusion: Reported cases confirm that there was a certain off-label use of EPs 7630 for COVID-19 in the market. Even though no formal conclusions about the efficacy of EPs 7630 in COVID-19 can be drawn, a beneficial effect would be explainable by the pharmacological profile of the extract. Further assessment of the effects of EPs 7630 in COVID-19-related indications therefore appears to be both justified and promising, particularly as the available case reports did not give rise to any safety concerns also in this patient group.

Safety and Outcomes of the Off-Label Treatment of Intracranial Aneurysms with Pipeline Embolization Device: A Systematic Review and Meta-analysis.

BACKGROUND: Off-label use of pipeline embolization devices (PEDs) has been increasingly used for endovascular treatment of intracranial aneurysms. Numerous articles have highlighted the safety and effectiveness of PED placement from independent centers for both on- and off-label indications. There remains a paucity of information that considers overall safety and efficacy of off-label PED placement across the existing literature. Our objective is to systematically review the safety and occlusion outcomes of PED off-label use in intracranial aneurysm embolization. METHODS: A systematic search of PubMed and Embase was performed to identify studies on off-label use of PED. The selected studies provided relevant information, including study characteristics, patient demographics, clinical outcomes, peri-procedural complications, and long-term outcomes, which were subjected to meta-analysis. RESULTS: Twelve studies met the inclusion and exclusion criteria. There were 747 patients and 791 aneurysms included for analysis. Among the patient, 69.2% were female, with an age range of 16 to 80 years. The overall incidence rates for ischemic and hemorrhagic complications were 7% (95% CI: 4%-10%) and 2% (95% CI: 0%-4%), respectively. The mortality rate was 1% (95% CI: 0%-4%). The occlusion rates of aneurysm at initial follow up and 1 year follow-up were 82% (95% CI: 72%-91%) and 81% (95%CI: 75%-86%), respectively. Meta-regression analysis indicated no correlation between occlusion rate and factors such as age, sex, aneurysm size, location, morphology, rupture, or history of treatment. CONCLUSIONS: Despite variations in results observed in single-center studies, this meta-analysis provides evidence supporting the safety and efficacy of PED off-label use.

Syringes for intraocular administration: Systematic review. / Jeringas para administración intraocular: revisión sistemática.

OBJECTIVE: The off-label use in clinical practice of non-approved syringes for intravitreal drug administration has resulted in the detection of silicone oil drops in the vitreous of some patients. This situation derives from the lack of approved syringes for intraocular use in the Spanish market. The aim of this work is to review the use of syringes for intraocular administration, as well as to search for alternatives that meet the legal requirements for these unmet needs. METHOD: A systematic review was performed following the PRISMA 2020 Guidelines by searching PubMed with the descriptors: "silicone" AND "syringes" AND ("intraocular" OR "intravitreal") and filtering all existing publications from January 2006 to December 2023, including all those articles dealing with silicone oil release in intravitreal injections and analysing the possible consequences. RESULTS: Sixty-eight results were found, 23 of which were excluded because they did not deal with the subject under study, leaving a total of 45 articles for the systematic review. These were classified according to the conclusions obtained in 4 groups: the adverse reactions produced by silicone, the administration technique, the physicochemical aspects of silicone release, and the characteristics of the medical device. After reviewing the current manufacturers and technical data sheets of commercialized syringes, the existing syringes for this use have been collected, finding two that will probably be commercialized in Spain at the beginning of 2024: Zero Residual™ 0.2 ml SiO-free and VitreJect® Ophthalmic. CONCLUSIONS: From the results obtained, it can be interpreted that the use of syringes and needles with silicone for intravitreal use is a concern for health professionals due to the implications and consequences that may arise in patients, the most important being adverse reactions, so it is necessary to have silicone-free syringes on the market that are specific for intraocular use. Safety and legality in the use of intraocular syringes and needles is essential to guarantee ocular integrity and patient health.

Repurposing of rituximab biosimilars to treat B cell mediated autoimmune diseases.

Rituximab, the first monoclonal antibody approved for the treatment of lymphoma, eventually became one of the most popular and versatile drugs ever in terms of clinical application and revenue. Since its patent expiration, and consequently, the loss of exclusivity of the original biologic, its repurposing as an off-label drug has increased dramatically, propelled by the development and commercialization of its many biosimilars. Currently, rituximab is prescribed worldwide to treat a vast range of autoimmune diseases mediated by B cells. Here, we present a comprehensive overview of rituximab repurposing in 115 autoimmune diseases across 17 medical specialties, sourced from over 1530 publications. Our work highlights the extent of its off-label use and clinical benefits, underlining the success of rituximab repurposing for both common and orphan immune-related diseases. We discuss the scientific mechanism associated with its clinical efficacy and provide additional indications for which rituximab could be investigated. Our study presents rituximab as a flagship example of drug repurposing owing to its central role in targeting cluster of differentiate 20 positive (CD20) B cells in 115 autoimmune diseases.

Off-label: The results of adjunctive bone morphogenetic protein for challenging femur fractures; a review of two cases.

Background: Although bone morphogenetic proteins (BMPs) are used as an adjunct to promote healing, they may have unintended effects such as heterotopic ossification (HO). The literature is limited regarding the effect of using off-label BMPs for femur fractures. Case presentation: We report two outcomes after off-label use of BMPs for the treatment of femur fractures and propose a possible explanation for the difference. Conclusions: BMPs are critical osteoinductive factors in injured bone and muscle that facilitate bony healing. However, it may be important to recognize the potentially negative effects of adding BMP to bone graft material in certain cases to stimulate bone repair. We hope this case series helps surgeons consider the risks and benefits of using BMP for femur fractures, and therefore to decide with caution when BMP is indicated.

Real-world treatment outcomes of immune checkpoint inhibitors used off-label in oncology: A comprehensive cancer institution experience.

Off-label use (OLU) is quite common in oncology due to the complexity of cancer and the time-consuming regulatory process. However, outcomes of OLU in cancer treatment remain unclear. This study aimed to evaluate the overall survival (OS), event-free survival (EFS), duration of treatment (DOT), and reason for treatment discontinuation in patients receiving immune checkpoint inhibitors (ICI) as OLU for solid tumors from 2011 to 2020. The study collected data on 356 episodes (353 patients), with a median age of 64.4 years, 36.2% women, and 14.6% ECOG ≥ 2. Median OS was 15.7 (11.9-18.7) months, and median EFS was 5.4 (3.8-6.6) months. Men, patients with metastatic disease or ECOG-PS higher than 1, had worse survival outcomes. The findings derived from this study provide valuable information regarding the real-world use of ICI-OLU and contributes to enhancing the decision-making process for individuals with cancer. Further research on immunotherapy outcomes of OLU in cancer is needed.

How to handle off-label prescriptions of rupatadine, a second-generation antihistamine and PAF antagonist: a review.

The off-label use of second-generation antihistamines, used outside of the formal indications authorized by regulatory authorities, in different age groups, doses or in special populations, is very common for many allergic, autoimmune and dermatological diseases. The off-label use of rupatadine (a second-generation antihistamine with PAF antagonist activity) in these conditions is reviewed here, including in combination with immunotherapy in the treatment of food allergy or allergic rhinitis, at high doses in chronic urticaria, and with prescriptions of less common but challenging conditions such as skin pruritus or mast cell activation disorders like mastocytosis. Rupatadine use is reviewed herein to confirm if its off-label management is supported by well-designed clinical trials or by published real-world cases. This review will contribute to increasing compliance and achieving better results in clinical practice. Off-label use of rupatadine should be left to the discretion of the prescribing healthcare professional after careful clinical evaluation.