Drug Substitution Research Articles

Safety of Rituximab biosimilar (Riximyo®) following a single switch from the reference product in patients with Non-Hodgkin’s lymphoma: a retrospective study

Unlike small molecule drugs and generic products, the active component of biologics and biosimilars are not identical chemical entities. Despite bioequivalence, there is limited evidence in clinical practice (i.e. Phase IV post-marketing surveillance) regarding the safety of biosimilar rituximab and even less so for “switching therapy” with respect to safety. Drug substitution by switching aims to realise cost savings by changing therapy involving a reference (biologic) product to a biosimilar. A retrospective analysis of safety outcomes including treatment-emergent adverse effects (TEAEs), rates of death and discontinuation of therapy, for all patients that received switching therapy (from reference to biosimilar rituximab, n = 33) was compared to patients who did not did not switch therapy (received biosimilar rituximab only, n = 18) at an Australian metropolitan cancer centre, over a six-month period. There was no statistical significant differences for any safety outcomes examined. Switching therapy for patients receiving rituximab does not lead to poorer safety outcomes.

Concomitant Administration of Psychotropic and Prostate Cancer Drugs: A Pharmacoepidemiologic Study Using Drug-Drug Interaction Databases.

Prostate cancer (PC) represents the second most common diagnosed cancer in men. The burden of diagnosis and long-term treatment may frequently cause psychiatric disorders in patients, particularly depression. The most common PC treatment option is androgen deprivation therapy (ADT), which may be associated with taxane chemotherapy. In patients with both PC and psychiatric disorders, polypharmacy is frequently present, which increases the risk of drug-drug interactions (DDIs) and drug-related adverse effects. Therefore, this study aimed to conduct a pharmacoepidemiologic study of the concomitant administration of PC drugs and psychotropics using three drug interaction databases (Lexicomp®, drugs.com®, and Medscape®). This study assayed 4320 drug-drug combinations (DDCs) and identified 814 DDIs, out of which 405 (49.63%) were pharmacokinetic (PK) interactions and 411 (50.37%) were pharmacodynamic (PD) interactions. The most common PK interactions were based on CYP3A4 induction (n = 275, 67.90%), while the most common PD interactions were based on additive torsadogenicity (n = 391, 95.13%). Proposed measures for managing the identified DDIs included dose adjustments, drug substitutions, supplementary agents, parameters monitoring, or simply the avoidance of a given DDC. A significant heterogenicity was observed between the selected drug interaction databases, which can be mitigated by cross-referencing multiple databases in clinical practice.

Substance abuse in Bhopal: An epidemiological survey

Background: Substance abuse has become a significant problem worldwide, affecting both developed and developing countries. In India, the situation is particularly concerning, with a likelihood of further increase in drug abuse and substitution of more potent drugs due to rapid industrialization and urbanization. Methods: Descriptive Survey Research was carried out among Seventy males of different De-addiction and Rehabilitation centers in Bhopal during the period of 19 November to 18 December 2022. A Predesigned and Pretested questionnaire was used to collect information from the Respondents. Results: Majority of the Respondents come from a background where the family or friends were into Drugs. Most of the Substance Users exist between the age group of 21-30 years. The major reason for the initiation of Drug according to the study was Curiosity and Enjoyment, and the major Source for initiation of Drugs were Friends (accounting to 86%) and Families (7%) respectively. Large number of the Respondents were Multi addicts followed by Alcohol, Ganja/Weed, Opioid and Cocaine Users. Conclusion: The study emphasizes the need for comprehensive approaches to address the underlying reasons of substance abuse, including community and family engagement. This study highlights the complexity of substance abuse, with multiple factors driving drug initiation, including curiosity, external persuasion, and psychological stress.

Real-World Use of Off-Label MVASI in the Treatment of Patients With Neovascular AMD and DME.

The purpose of this study was to evaluate the efficacy and safety of bevacizumab-awwb in the off-label treatment of neovascular age-related macular degeneration (n-AMD) and diabetic macular edema (DME). All patients with n-AMD and DME treated in the maintenance phase according to the "treat and extend" strategy, who underwent forced drug substitution from bevacizumab to bevacizumab-awwb from October 2022 to April 2023 at the Tor Vergata Polyclinic in Rome, were evaluated in a retrospective study. The primary outcome was changes in central retinal thickness (CRT) over time following drug substitution. The secondary outcomes were variations in drug durability, best corrected visual acuity (BCVA) and retinal fluid, and the incidence of drug-related local and systemic serious adverse events. Of 80 eyes of 76 patients with n-AMD and 55 eyes of 44 patients with DME included, before and after drug substitution, the average CRT did not statistically differ; the proportion of patients within time intervals of q8, q12, and q16 was not different; and the mean BCVA remained constant. Of a cumulative 3496 bevacizumab-awwb treatments (2154 for patients with n-AMD and 1342 for patients with DME), no local severe complications were detected. Out of a total of 544 patients (342 affected by n-AMD and 202 affected by DME), no serious adverse events were reported. In our cohort of patients with n-AMD and DME in the maintenance phase, bevacizumab-awwb seems to represent a viable and cost-effective intravitreal therapy with comparable efficacy and safety to the originator. This study provides a preliminary assessment of the efficacy and safety of intravitreal bevacizumab-awwb, which is widely used off-label in retinal vascular diseases.

A novel near-infrared-II fluorescence probe for serum albumin biosensing and site-binding mechanism study

Abnormal albumin levels are predictors of nephropathy, liver cirrhosis, coronary heart disease, and diabetes. Sensitive and rapid detection of endogenous albumin is of great significance to disease diagnosis and new drug discovery. Here, the first near-infrared-II fluorescence probe for albumin was developed. Based on the remarkable fluorescence enhancement induced by albumin, both human serum albumin (HSA) and bovine serum albumin (BSA) were quantified in several minutes. The limit of detection for albumin in urine samples is as low as 50 nM, which meets the requirement well for clinical analysis. The fluorescence imaging of drug-induced albumin in living cells verified strong capability for the probe to monitor the endogenous albumin. The site-binding mechanism between the probe and albumin was investigated via Job's plots analysis, drug substitution assays, and molecular docking. The NIR-II probe exhibits a specific and high-affinity binding (Kb=5.26×1011 M−1) with albumin, which enabled a further determination of trypsin and a protease inhibitor. This novel versatile biosensor provides a promising strategy for on-site evaluating of endogenous albumin for clinical diagnostics and drug screening.

Antibacterial resistance and the cost of affecting demand: The case of UK antibiotics

Consumption of broad-spectrum antibiotics is associated with rising antimicrobial resistance (AMR) levels. The use of broad-spectrum drugs, particularly of cephalosporins, quinolones, and co-amoxiclav contributes the most to the rise in AMR. We use aggregate sales data on antibiotics from the UK to estimate structural demand models and reveal drug substitution patterns. We then simulate alternative tax schemes to evaluate the effectiveness of shifting demand from broad- to narrow-spectrum drugs. Our estimates suggest that these policies can be highly effective in demand management and come at a relatively low cost regarding changes in consumer and producer surplus.

Opioid Use, Mortality Risks and Crime: Insights from a Rapid Reduction in Heroin Supply

Abstract In 2001, a large and sustained supply shock halted a heroin epidemic in Australia. We use drug offenses to identify individual opioid users and examine how the shock affected their mortality risks and criminal activity over the next eight years. Initially, gains from fewer overdoses are offset by drug substitution and more crime, including homicides. Most adverse effects dissipate over time, while persistent mortality reductions save the lives of around one in 48 individuals in our sample. Our results demonstrate that reducing the supply of illicit opioids can lead to meaningful longer-term improvements, even when the short-term effects are ambiguous.

Barriers to access to hepatitis C treatment with direct-acting antivirals in people who inject drugs in the community setting

Barriers to access to hepatitis C treatment with direct-acting antivirals in people who inject drugs in the community setting. Qualitative study with prison population. Hepatitis C (HCV) treatments with direct-acting antiviral therapy (DAA) are an easy and effective option among people who inject drugs (PWID). However, difficulties in accessing and monitoring treatment in community services and dropouts on release from prison are detected among PWID. For this reason, the aim of the study is to know the access barriers in the diagnosis and treatment of HCV in community health services. An exploratory qualitative study was carried out through semi-structured interviews with 33 PWID recruited in a pre-trial detention prison in Barcelona. The information obtained was analysed using grounded theory. Among PWID sub-population entering prison, personal barriers are related to intense drug use, lack of interest and ignorance of HCV infection and treatment, as well as being in a situation of social exclusion. In relation to health providers, they reported receiving little information, the existence of language barriers in migrants, not receiving screening and treatment proposals, and having poor interactions with some professionals. Systemic barriers were expressed related to the health system circuit being complicated, perceiving little comprehensive care and lack of community support. It is recommended to intensify prevention and treatment campaigns, promoting drug substitution programmes than current ones, improve health education, make the diagnosis and treatment process more flexible, and promote social policies and holistic care for greater coverage of the needs of PWID.

Reduced emergency department use among insured individuals receiving extended-release buprenorphine in a health system setting

IntroductionExtended-release buprenorphine (XR-Bup) is associated with reduced opioid use and opioid negative urine drug screens. Little is known about its use in outpatient addiction care provided within health systems. MethodsIndividuals prescribed XR-Bup were identified from electronic health records; chart abstraction was conducted. Primary outcome was all-cause emergency department (ED) use. Secondary outcomes included ED use or inpatient stays for mental health or substance use, ED use for any other cause, discontinuation reasons, and drug substitution. Statistical comparisons used nonparametric tests from related samples (McNemar’s test and Wilcoxon matched pair tests) to test outcomes six months prior and 6 months following XR-Bup initiation. Results152 individuals had an XR-Bup order, 126 received >1 injection. Among those consistently insured 6 months prior to and following XR-Bup initiation (n=99), the mean number of injections following initiation was 3.95; one-third received 6 doses in the 6 months. The proportion of individuals using ED services for all causes declined (41% prior vs. 28% following XR-Bup initiation, p<.05); similar results were found for secondary ED use outcomes. The proportion of individuals requiring inpatient treatment for mental health or substance use also declined (46% vs. 16%, p<.01). Common reasons for discontinuing XR-Bup included losing insurance (21%) or cost (11%). The most common non-prescribed substances used during treatment were opioids (n=31) and THC (n=20). ConclusionsIn this non-randomized retrospective observational study, use of XR-Bup was associated with reduced ED use 6 months following initiation. XR-Bup may help health systems reduce use of costly ED services.

Viral suppression with antiretroviral therapy after single drug substitution of efavirenz with dolutegravir at an HIV Centre in Karachi, Pakistan

Background: AIDS was first reported in the 1980s. The HIV prevalence rate among Pakistani adults is 0.2%. The Sindh Center for AIDS Control Programs (SACP) was established in Karachi in 2006. In 2018, the SACP introduced the integrase chain transfer inhibitor dolutegravir (DTG) and lamivudine (3TC) and tenofovir diproxilfumarate (TDF). Patients who developed virological failure on Efavirenz, 3TC, and TDF were switched to DTG/3TC/TDF. As the two nucleoside reverse transcriptase inhibitors remained the same, EFV and DTG were effectively substituted as single agents. We assessed immunological, virological and clinical responses to DTG. Material and Methods: A retrospective chart review was conducted at the SACP of adults with virological failure on EFV/3TC/TDF who were switched to DTG/3TC/TDF from April 2019 till November 2023. Results: The 14 patients were switched after a mean of 28.2 months of prior antiretroviral therapy with mean CD4 of 116 cells/mm3. Mean age was 28.4 years with 7 (50.0%) males.12 were adherent to the DTG regimen; 11 (92 %) achieved viral suppression. The Mean period of suppression was31 months. There was no clinical or immunological failure with upsurge of mean CD4 to 632 cells/mm3. Conclusion: The patients with virological failure on an efavirenz-based regimen are likely to have viral suppression after switch to a dolutegravir-based routine even if they potentially have NRTI resistance. These results are relevant to HIV programs in resource-poor settings where switches between regimens are often implemented without frequent viral load or resistance testing. Keywords: HIV, Dolutegravir, Efavirenz, Tenofovir, Viral suppression, CD4 count

Roots Cause of the Drug Shortage and Expired Drug Problem at Hospital X

Good drug management in the Hospital Pharmacy Installation is the key to the smooth running of pharmaceutical services. The availability of the necessary drugs at the right time and place affects patient safety and satisfaction. Empty drugs and expired drugs are problems in drug management, mainly Hospital X. Empty drugs result in the replacement of drugs in prescriptions, thus increasing the burden on pharmaceutical services and creating risks for patient safety. Expired drugs cause hospital losses. This study aims to describe the root cause of drug shortages and expired drugs in Hospital X. The research used a qualitative approach to dig deeper into these complex problems—elicitation of data using semi-structured interviews supported by secondary data from the hospital. Data were analyzed using a Fishbone diagram to get a systematic overview of the root causes of problems based on specific domains. The root causes of expired drug problems and empty drug substitution in Hospital X are materials/inputs, methods, people, machinery/equipment, measurement (process evaluation), and the pharmacy facility environment domains.

Amlodipine-Induced Gingival Enlargement – A Case Report

One of the etiological factors for Gingival Enlargement is administration of certain drugs like calcium channel blockers, anticonvulsants, and immunosuppressant. The drug that is been commonly used for the management of portal hypertension is calcium channel blockers. Among the various drugs in calcium channel blockers, the occurrence of drug-induced gingival enlargement is high with the use of nifedipine drug whereas the occurrence of gingival enlargement due to the usage of amlodipine drug is a very rare phenomenon. Amlodipine is a third-generation drug belonging to dihydropyridine calcium channel blocker that has been used for its longer duration of action. Treatment for drug-induced gingival enlargement includes referral of patients to their physician for possible drug substitution or alteration in dosage of drug, periodontal therapy that includes oral prophylaxis followed by gingivectomy or gingivoplasty, and maintenance care. In this study, we report a case of gingival enlargement in a 44-year-old female patient taking amlodipine drug for a period of six months and nonsurgical and surgical management of amlodipine-induced gingival enlargement in the patient.

Adulteration and substitution of drugs purchased in Australia from cryptomarkets: An analysis of Test4Pay.

Prohibited drugs in unregulated markets may be adulterated, resulting in increased risks for people who use drugs. This study investigated levels of drug adulteration and substitution of drugs purchased in Australia from cryptomarkets. Data were collected from a darknet forum called Test4Pay from 1 September 2022 to 23 August 2023. Posts were included if they reported the results of drug samples submitted by post to the Vancouver-based Get Your Drugs Tested service, which uses Fourier-transform infrared spectroscopy with immunoassay strip tests (fentanyl and benzodiazepines). Of 103 samples, 65% contained only the advertised substance, 14% contained the advertised substance in combination with other psychoactive and/or potentially harmful substances and for 21%, the advertised substance was absent. Substances sold as MDMA, methamphetamine or heroin were consistently found to contain only the advertised substance, while substances sold as 2C-B, alprazolam or ketamine were the most likely to be completely substituted. Only 4 samples sold as cocaine contained solely the advertised substance, with 13 containing cocaine with adulterants like lidocaine, creatine, levamisole and boric acid (n = 19). No fentanyl contamination was detected. Novel dissociatives and novel benzodiazepines were detected, as well as a nitazene compound. Drug markets under prohibition continue to contain numerous unexpected substances, some of which can elevate risk of harm. Cryptomarkets are not immune to this problem, despite review systems, which should, in theory, make vendors more accountable for the quality of their stock. These findings demonstrate a need for expansion of local drug checking services in Australia.

Rhenium(I) coordinated carbon nitride as type II immunogenic cell death inducers for enhancing photoimmunotherapy against triple-negative breast cancer

Immunotherapy is a promising modality for treating triple-negative breast cancer (TNBC). However, its therapeutic effect is severely restricted by the drug resistance and non-immunogenic tumor microenvironment. Herein, an endoplasmic reticulum (ER)-targeting rhenium(I) coordinated carbon nitride photosensitizer based on Re(CO)5Cl coordinated to g-C3N4 nanosheets can realize photoimmunotherapy against hypoxic-drug resistant TNBC. Compared with the clinical anti-cancer chemotherapy drug doxorubicin, the photosensitizer induces robust ER stress to evoke damage-associated molecular patterns (DAMPs) exposure on the cell surface by a combinatorial interaction mechanism of apoptosis, pyroptosis, ferroptosis, and ICD under two-photon light irradiation. The DAMPs can stimulate the antigen-presenting function of dendritic cells. As a result, a series of immunological responses are activated, including CD8+ and CD4+ T cell proliferation, which effectively inhibited the growth of the primary and secondary distant tumor in vivo. In all, we present a light-dependent type II ICD inducer of metal-based complexes that can conquer drug resistance for hypoxic TNBC, which may have great potential in the substitution of clinical anticancer drugs.

Impacts of national volume-based drug procurement policy on the utilization and costs of antihypertensive drugs in a Chinese medicine hospital: an interrupted time series analysis of 5138 patients.

Objectives: The study aimed to estimate the effects of National Volume-based Drug Procurement (NVBP) policy on drug utilization and medical expenditures of hypertension patients in public medical institutions in mainland China. Methods: This study used patient-level data based on electronic health records retrieved from the hospital information system of Nanjing Hospital of Chinese Medicine. Data on patients with hypertension who received care at this institution between 2016 and 2021 was used for analysis. Segmented linear regression models incorporating Interrupted Time Series (ITS) analysis were adopted to examine the effects of NVBP policy on drug utilization and health expenditures of eligible patients. Drug utilization volume and health expenditures were the primary outcomes used to assess the policy effects, and were measured using the prescription proportion of each drug class and the overall per-encounter treatment costs. Results: After the implementation of NVBP policy, the volume of non-winning drugs decreased from 54.42% to 36.25% for outpatient care and from 35.62% to 15.65% for inpatient care. The ITS analysis showed that the volume of bid-winning drugs in outpatient and inpatient settings increased by 9.55% (p < 0.001) and 6.31% (p < 0.001), respectively. The volume changes in non-volume based purchased (non-VBP) drugs differed between outpatients and inpatients. The proportion of non-VBP drugs immediately increased by 5.34% (p = 0.002) overall, and showed an upward trend in the outpatient setting specially (p < 0.001) during the post-intervention period. However, no significant differences were observed in the proportion of non-VBP drugs in inpatient setting (p > 0.05) in term of level change (p > 0.05) or trend change (p > 0.05). The average per-visit expenditures of outpatients across all drug groups exhibited an upward trend (p < 0.05) post policy intervention. In addition, a similar increase in the overall costs for chemical drugs were observed in inpatient settings (coefficient = 2,599.54, p = 0.036), with no statistically significant differences in the regression slope and level (p = 0.814). Conclusion: The usage proportion of bid-winning drugs increased significantly post policy intervention, indicating greater use of bid-winning drugs and the corresponding substitution of non-winning hypertensive drugs. Drug expenditures for outpatients and health expenditures per visit for inpatients also exhibited an upward trend, suggesting the importance of enhanced drug use management in Traditional Chinese Medicine hospital settings.

Pregled lista i preporuka za zamenljivost lekova u izabranim evropskim zemljama

Generic substitution has been introduced in the healthcare systems of many countries to reduce the costs and ensure the continuity of drug market supply. Common and country-specific strategies on this topic have been presented for several European countries, as well as for the Republic of Serbia. The factors that need to be considered when assessing the interchangeability of medicines may be related to the medicine or the individual patient. Particular caution is required with narrow therapeutic index drugs, drugs with non-linear pharmacokinetics, antiepileptic drugs, medicines with prolonged release formulations, medicines administered in a specific way or with a medical device. Factors such as the different appearance of the medicines, excipients, packaging, indications, but also the patient's condition, age, concomitant diseases, pregnancy, hand function, vision, ability to swallow, and the patient's attitude towards the alternative medicines should also be taken into account. When substituting two generic medicines, it should be noted that those medicines may not be bioequivalent, since bioequivalence is confirmed between a generic medicine and a reference (usually original) medicine, and thus pose an additional risk to the patient's safety. Some countries have opted to form lists of interchangeable medicines and/or detailed guidelines regarding interchangeability to assist healthcare professionals in making decisions on drug substitution.

Generic orphan drug substitution: a critical analysis of global practices and Saudi Arabia's perspective.

In an era of cost pressure, substituting generic drugs represents one of the main cost-containment strategies of healthcare systems. Despite the obvious financial benefits, in a minority of cases, substitution may require caution or even be contraindicated. In most jurisdictions, to obtain approval, the bioequivalence of generic products with the brand-name equivalent needs to be shown via bioavailability studies in healthy subjects. Rare diseases, defined as medical conditions with a low prevalence, are a group of heterogenous diseases that are typically severe, disabling, progressive, degenerative, and life-threatening or chronically debilitating, and disproportionally affect the very young and elderly. Despite these unique features of rare diseases, generic bioequivalence studies are typically carried out with single doses and exclude children or the elderly. Furthermore, the excipients and manufacturing processes for generic/biosimilar products can differ from the brand products which may affect the shelf-life of the product, its appearance, smell, taste, bioavailability, safety and potency. This may result in approval of generics/biosimilars which are not bioequivalent/comparable in their target population or that meet bioequivalence but not therapeutic equivalence criteria. Another concern relates to the interchangeability of generics and biosimilars which cannot be guaranteed due to the phenomenon of biocreep. This review summarizes potential concerns with generic substitution of orphan drugs and discusses potentially problematic cases including narrow therapeutic index drugs or critical conditions where therapeutic failure could lead to serious complications or even death. Finally, we put forward the need for refining regulatory frameworks, with emphasis on Saudi Arabia, for generic substitution and recent efforts toward this direction.

AUTHENTICATION OF SOME COMMERCIAL TEAS IN ILORIN, NORTH-CENTRAL, NIGERIA

Adulteration and substitution of herbal drugs are trending issue in the herbal industry, posing a serious threat to commercial natural product research. Anatomical and chemical studies were carried out on Camellia sinensis and 6 commercial tea samples using chemical maceration technique (C-tea, L-tea, T-tea, H-tea, N-tea and A-tea). C. sinensis has hypostomatic leaves with paracytic and anomocytic stomatal complex types and thick-cell wall. The plant also possessed non-glandular unicellular trichomes. The anticlinal wall pattern was straight and rectangular, and it is undulating on the adaxial surface. Anatomically, C-tea has paracytic and pericytic stomatal complex types and unicellular non-glandular and multicellular glandular trichomes. L-tea has paracytic and anomocytic with unicellular glandular and multicellular non glandular trichomes. Paracytic, polocytic and anisocytic stomatal complex types with unicellular glandular and multicellular non-glandular trichomes were observed in T-tea. Occurrence of paracytic and anomocytic stomata was observed in H-tea; paracytic and tetracytic stomata were present in N-tea while paracytic stomata were observed in A-tea with unicellular glandular trichomes. The chemical tests shown that Prussian blue was present in three commercial samples of black tea and turmeric was present in two commercial green tea samples. Anatomical studies revealed that four of the selected commercial tea samples shown traces of adulteration.

PHARMACOGNOSTIC EVALUATION OF APIUM GRAVEOLENS LINN. AND TRACHYSPERMUM ROXBURGHIANUM (DC.) CRAIB.: THE DRUG “AJMODA” IN INDIAN SYSTEM OF MEDICINE

Two species, namely, Apium graveolens Linn. and Trachyspermum roxburghianum (DC.) Craib., are being popularly known as ‘Ajmoda’ in India and ‘Celery’ in English. Both the species belong to the family Apiaceae. The plant specimens are mostly collected from wild sources by unskilled collectors on the basis of the local names, which leads to adulteration and substitution for genuine drugs. There is a chance of improper identification because of similar name. The seeds of these species are morphologically very similar and it is difficult to identify because of their smaller size. Therefore, this study aims to find out the detailed pharmacognostical evaluation to differentiate the seeds of the two species on the basis of microscopic characters, fluorescence analysis, physicochemical values and TLC fingerprint profile.

A risk-based approach to community illicit drug toxicosurveillance: operationalisation of the Emerging Drugs Network of Australia – Victoria (EDNAV) project

IntroductionThe Emerging Drugs Network of Australia – Victoria (EDNAV) project is a newly established toxicosurveillance network that collates clinical and toxicological data from patients presenting to emergency departments with illicit drug related toxicity in a centralised clinical registry. Data are obtained from a network of sixteen public hospital emergency departments across Victoria, Australia (13 metropolitan and three regional). Comprehensive toxicological analysis of a purposive sample of 22 patients is conducted each week, with reporting of results to key alcohol and other drug stakeholders. This paper describes the overarching framework and risk-based approach developed within Victoria to assess drug intelligence from EDNAV toxicosurveillance. MethodsRisk management principles from other spheres of public health surveillance and healthcare clinical governance have been adapted to the EDNAV framework with the aim of facilitating a consistent and evidence-based approach to assessing weekly drug intelligence. The EDNAV Risk Register was reviewed over the first two years of EDNAV project operation (September 2020 – August 2022), with examples of eight risk assessments detailed to demonstrate the process from signal detection to public health intervention. ResultsA total of 1112 patient presentations were documented in the EDNAV Clinical Registry, with 95 signals of concern entered into the EDNAV Risk Register over the two-year study period. The eight examples examined in further detail included suspected drug adulteration (novel opioid adulterated heroin, para-methoxymethamphetamine adulterated 3,4-methylenedioxymethamphetamine (MDMA)), drug substitution (25B-NBOH sold as lysergic acid diethylamide, five benzodiazepine-type new psychoactive substances in a single tablet, protonitazene sold as ketamine), new drug detection (N,N-dimethylpentylone), contamination (unreported acetylfentanyl) and a fatality subsequent to MDMA use. A total of four public Drug Alerts were issued over this period. ConclusionsContinued toxicosurveillance efforts are paramount to characterising the changing landscape of illicit drug use. This work demonstrates a functional model for risk assessment of illicit drug toxicosurveillance, underpinned by analytical confirmation and evidence-based decision-making.