Impact of drug formulation on outcomes of pharmaceutical poisoning in children aged 7 years or younger: A retrospective observational study in South Korea.

ABSTRACT: Pharmaceutical poisoning in children is almost unintentional and there are various types of drug out of curiosity. Understanding the attractive features and formulation of drugs related to poisoning in younger children may be helpful in treatment and prevention of poisoning. To investigate the impact of drug formulation on outcomes of pharmaceutical poisoning in young children.We retrospectively reviewed the data of pharmaceutical exposures among children who were registered in a Korean 23-center, emergency department (ED) based registry from 2011 to 2016. Our study was conducted on preschool children aged 0 to 7 years. According to the formulation and category of the ingested drugs, the exposures were divided into the "tablet and capsule (TAC)" and "syrup" groups. In the TAC group, we additionally recorded data on the shape, color, and size of the drugs. The ED outcomes, such as hospitalization and length of stay, were compared between the 2 groups.Among the 970 enrolled exposures, 674 (69.5%) were classified into the TAC group. In this group, hormones/hormone antagonists (18.5%) were the most commonly ingested, followed by central nervous system drugs (17.1%). In the syrup group, antihistamines (28.4%) were the most commonly ingested, followed by respiratory drugs (24.3%). The TAC group showed a higher hospitalization and transfer rate to tertiary centers than the counterpart (TAC, 18.0% vs syrup, 11.5%, P = .03) without a significant difference in the length of stay (TAC, 173.5 minutes [interquartile range, 95.0-304.0] vs syrup, 152.5 [77.5-272.0]; P = .08). No in-hospital mortality occurred in the exposures. Round-shaped and chromatic TACs, accounting for 91.7% (618) and 56.1% (378), respectively, were more commonly ingested. The median size of the TACs was less than 1.0 cm.Young children who visited the ED ingested TACs more frequently than syrups, particularly small, round-shaped, or chromatic drugs, leading to a higher hospitalization rate. Our findings can contribute to prevention strategies and safety education on childhood drug poisoning.

A Review of the Main Considerations for Formulation Development in Preclinical Toxicology Studies.

The main considerations for the development of a formulation for preclinical safety assessment testing are explored. Intravenous, inhalation, oral and dermal dosing are given focus and although different dose routes do present their own individual challenges there are common themes that emerge. In each case it is necessary to maximise exposure to achieve high doses to satisfy regulatory requirements for safety assessment testing. This often involves producing formulations that are at the limits of solubility and maximum volumes possible for administration to different test species by the chosen route. It is concluded that for all routes it is important to thoroughly explore the stability of the test item in the proposed formulation matrix well ahead of dosing any animals, giving careful consideration to which excipients are used and what their underlying toxicity profile may be for the relevant preclinical species. In addition, determining the maximum achievable concentrations and weighing that against the maximum volumes that can be given by the chosen route in all the test species at an early stage will also give a read on whether it would be theoretically possible to achieve suitably high enough doses to support clinical work. Not doing so can cause delays in the development programme and may have ethical repercussions.

H7N9 pandemic preparedness: A large-scale production of a split inactivated vaccine.

In March 2013 it was reported by the World Health Organization (WHO) the first cases of human infections with avian influenza virus A (H7N9). From 2013 to December 2019, 1568 cases have been reported with 616 deaths. H7N9 infection has been associated with high morbidity and mortality rates, and vaccination is currently the most effective way to prevent infections and consequently flu-related severe illness. Developing and producing vaccines against pandemic influenza viruses is the main strategy for a response to a possible pandemic. This study aims to present the production of three industrial lots under current Good Manufacturing Practices (cGMP) of the active antigen used to produce the pandemic influenza vaccine candidate against A(H7N9). These batches were characterized and evaluated for quality standards and tested for immunogenicity in mice. The average yield was 173.50 ± 7.88 µg/mL of hemagglutinin and all the preparations met all the required specifications. The formulated H7N9 vaccine is poorly immunogenic and needs to be adjuvanted with an oil in water emulsion adjuvant (IB160) to achieve a best immune response, in a prime and in a boost scheme. These data are important for initial production planning and preparedness in the case of a H7N9 pandemic.

Comparison of Safety Profiles of the New and Old Formulations of Levothyroxine in a First Global Introduction in France.

BACKGROUND: Levothyroxine sodium marketed in France was reformulated following a French National Agency for Medicines and Health Products Safety request for a more stringent potency specification. Despite previously established purity and bioequivalence of the new and old formulations, reports of adverse events substantially increased following reformulation. This analysis evaluated the nature and relevance of the medically confirmed safety reports. METHODS: Spontaneous and solicited individual case safety reports in France were retrieved from 26 March 2015 to 30 June 2016 (old formulation) and 26 March 2017 to 30 June 2018 (new formulation). Rates of reports and adverse events were calculated for the overall patient population and for at-risk subgroups. Adverse events delineated by thyroid-stimulating hormone levels were evaluated. RESULTS: A total of 295 and 42 775 reports for the old formulation and new formulation, respectively, were retrieved, with 149 and 5503 medically confirmed. The most common medically confirmed adverse events were consistent with the known safety profile of levothyroxine, with generally comparable rates between both formulations (range of differences, 1.8-4.1%). Most cases were not serious (old formulation, 65.8%; new formulation, 78.7%). Reporting rates were similar or higher for the old formulation within subgroups of at-risk patients. Nature/distributions of adverse events by thyroid-stimulating hormone levels as determined by both the marketing authorization holder of levothyroxine and the French National Agency for Medicines and Health Products Safety were similar. CONCLUSIONS: The new formulation safety profile aligns with the established profile of the old formulation of levothyroxine. The benefit-risk profile is unchanged, such that the benefits of using the new formulation in the approved indications outweigh the risks associated with the treatment.

Pharmacokinetics and Pharmacodynamics of Two Formulations of Pegylated Recombinant Human Granulocyte Colony-Stimulating Factor in Healthy Chinese Subjects: An Open-Label, Randomized, Parallel-Design Bioavailability Study.

Pegylated recombinant human granulocyte colony-stimulating factor (PEG-rhG-CSF, pegfilgrastim) is a long-acting derivative of recombinant human granulocyte colony-stimulating factor with limited renal clearance and a longer half-life. It is used for the prevention of febrile neutropenia, owing to its capacity to promote neutrophil recovery. In this study, the pharmacokinetics, pharmacodynamics, safety, and immunogenicity of 2 formulations of PEG-rhG-CSF were evaluated in healthy Chinese subjects. Twenty-four male subjects who received a single dose of subcutaneous PEG-rhG-CSF 100 µg/kg were randomized to either treatment A (3 mg/mL) or treatment B (1 mg/mL). Noncompartmental pharmacokinetic parameters of PEG-rhG-CSF were derived from serum concentration-time data. In addition, absolute neutrophil count (ANC) as a pharmacodynamic maker, immunogenicity through antidrug antibody testing, and safety were evaluated. The mean area under the concentration-time curve from time zero to the last quantifiable concentration (AUC0-t ) and the mean maximum concentration (Cmax ) of PEG-rhG-CSF after treatment A were 5070 ng·h/mL and 125 ng/mL, respectively; these values were comparable to those measured after treatment B (5340 ng·h/mL and 123 ng/mL, respectively). The mean value of area under the △ANC (baseline-adjusted ANC)-time curve and the maximum △ANC values were 4380 × 109  h/L and 33.1 × 109 /L, respectively, in the treatment A group, and 5170 × 109  h/L and 38.6 × 109 /L, respectively, in the treatment B group. The pharmacokinetic and pharmacodynamic profiles were similar for the 2 PEG-rhG-CSF formulations following a single dose of 100 µg/kg. The safety and immunogenicity profiles were also similar, with no significant differences. The dose adjustment of PEG-rhG-CSF was not considered necessary for formulation transformation.

Review of economic data on closed system transfer drug for preparation and administration of hazardous drugs.

OBJECTIVES: The objectives of this study were to review economic data on the use of closed system drug transfer devices (CSTDs) for preparing and administering hazardous drugs, and to evaluate the quality of data reporting as defined by the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). METHODS: All references from a recent Cochrane review about CSTDs were evaluated for inclusion. A literature review was also conducted. Articles containing economic data about the use of CSTDs were retained for analysis. Two researchers independently graded the articles according to the 24-item CHEERS checklist. RESULTS: Of the 138 articles identified initially, 12 were retained for analysis. Nine of these studies did not report acquisition costs or did not detail acquisition costs. Six studies reported economic benefits associated with the used of CSTDs, all related to extending the beyond-use date. The mean number of CHEERS criteria fulfilled by the included articles was 9.2 (SD 2.4). CONCLUSIONS: CSTDs are costly to acquire. However, few studies have examined the economic impact of these devices, and the existing studies are incomplete. As a result, hospitals planning to implement these devices will be unable to make a sound economic evaluation. Robust economic evaluation of CSTDs is needed.

A Comprehensive Scientific Survey of Excipients Used in Currently Marketed, Therapeutic Biological Drug Products.

PURPOSE: The steady development of biotechnology-derived therapeutic biologics over the last few decades has generated drugs that are now standard medical treatments for a range of indications. While the development of protein products has surged in recent years, the formulation and delivery of these complex molecules have relied on drug-specific studies and, in some instances, data from non-proteinaceous drug products. The commonalities, trends, and gaps in excipient technologies used to support the development of therapeutic proteins largely remain unexplored due to the drug-specific nature of many formulations. METHODS: Using a comprehensive and relational database approach, we aimed to provide a scientific survey of all approved or licensed biotechnology-derived drug products with the goal of providing evidence-based information on common attributes and trending features in protein product excipients. We examined 665 formulations, and 395 unique formulations based on having unique excipients within them, that supported 211 therapeutic proteins as of June 2020. RESULTS: We report the prevalence of each excipient class and excipient chemical used in eight different drug types including monoclonal antibodies, antibody conjugates, cytokines and growth factors, enzymes, polypeptide hormones, pulmonary surfactants, recombinant fusion proteins, and toxins. We also report the prevalence by excipient type among all therapeutic proteins, in the context of each drug's recommended pH range, concentration ranges for excipients, and route of administration. CONCLUSIONS: The results of our analyses indicate certain excipients common to monoclonal antibodies, cytokines, and polypeptide hormones. We also report on excipients unique to protein drug products, such as amino acids, solubilizers, and lyoprotectants. Overall, our report summarizes the current landscape of excipients used in marketed biotechnology-derived therapeutic biologic products.

Cost-Consequences Analysis of Increased Utilization of Triple-Chamber-Bag Parenteral Nutrition in Preterm Neonates in Seven European Countries.

The safety of parenteral nutrition (PN) remains a concern in preterm neonates, impacting clinical outcomes and health-care-resource use and costs. This cost-consequence analysis assessed national-level impacts of a 10-percentage point increase in use of industry-prepared three-chamber bags (3CBs) on clinical outcomes, healthcare resources, and hospital budgets across seven European countries. A ten-percentage-point 3CB use-increase model was developed for Belgium, France, Germany, Italy, Portugal, Spain, and the UK. The cost-consequence analysis estimated the impact on compounding error harm and bloodstream infection (BSI) rates, staff time, and annual hospital budget. Of 265,000 (52%) preterm neonates, 133,000 (52%) were estimated to require PN. Baseline compounding methods were estimated as 43% pharmacy manual, 16% pharmacy automated, 22% ward, 9% outsourced, 3% industry provided non-3CBs, and 7% 3CBs. A modeled increased 3CB use would change these values to 39%, 15%, 18%, 9%, 3%, and 17%, respectively. Modeled consequences included -11.6% for harm due to compounding errors and -2.7% for BSIs. Labor time saved would equate to 41 specialized nurses, 29 senior pharmacists, 26 pharmacy assistants, and 22 senior pediatricians working full time. Budget impact would be a €8,960,601 (3.4%) fall from €260,329,814 to €251,369,212. Even a small increase in the use of 3CBs in preterm neonates could substantially improve neonatal clinical outcomes, and provide notable resource and cost savings to hospitals.

Lymphatic Transport of Drugs after Intestinal Absorption: Impact of Drug Formulation and Physicochemical Properties.

PURPOSE: To provide a comprehensive and up-to-date overview focusing on the extent of lymphatic transport of drugs following intestinal absorption and to summarize available data on the impact of molecular weight, lipophilicity, formulation and prandial state. METHODS: Literature was searched for in vivo studies quantifying extent of lymphatic transport of drugs after enteral dosing. Pharmacokinetic data were extracted and summarized. Influence of molecular weight, log P, formulation and prandial state was analyzed using relative bioavailability via lymph (FRL) as the parameter for comparison. The methods and animal models used in the studies were also summarized. RESULTS: Pharmacokinetic data on lymphatic transport were available for 103 drugs. Significantly higher FRL [median (IQR)] was observed in advanced lipid based formulations [54.4% (52.0)] and oil solutions [38.9% (60.8)] compared to simple formulations [2.0% (27.1)], p < 0.0001 and p = 0.004, respectively. Advanced lipid based formulations also provided substantial FRL in drugs with log P < 5, which was not observed in simple formulations and oil solutions. No relation was found between FRL and molecular weight. There were 10 distinct methods used for in vivo testing of lymphatic transport after intestinal absorption so far. CONCLUSION: Advanced lipid based formulations provide superior ability to increase lymphatic absorption in drugs of various molecular weights and in drugs with moderate to low lipophilicity.

Pharmacokinetics and Bioequivalence Estimation of Two Formulations of Alfuzosin Extended-Release Tablets.

Alfuzosin is a medication approved by the US Food and Drug Administration to treat benign prostatic hyperplasia symptoms. Bioequivalence studies are demanded by regulatory authorities to evaluate the expected in vivo biological similarity of 2 formulations of a medication. The aim of this study is to assess the bioavailability of the generic (test) and branded (reference) formulations of 10-mg alfuzosin extended-release tablets after oral administration to healthy adults under fed conditions. The study used a comparative randomized, single-dose, 2-way crossover open-label study design. Thirty-three participants were recruited and completed the clinical assessment. The pharmacokinetic parameters maximum plasma concentration (Cmax ), area under the plasma concentration-time curve (AUC0-t ), AUC extrapolated to infinity (AUC0-∞ ), time to maximum concentration, and elimination half-life were estimated to prove bioequivalence. The confidence intervals for the log-transformed test/reference ratios for alfuzosin 110.7% (98.0-124.9) and 112.0% (101.9-123.1) for Cmax and AUC0-t respectively, which are within the allowed limits specified by the regulatory authorities (80-125% for Cmax and AUC0-t ). The test formulation can therefore be prescribed as an alternative to the reference for symptomatic treatment of benign prostatic hyperplasia.

Mucus-Penetrating Particles and the Role of Ocular Mucus as a Barrier to Micro- and Nanosuspensions.

The ocular surface is naturally covered with a layer of mucus. Along with other functions, this mucus layer serves to trap and eliminate foreign substances, such as allergens, pathogens, and debris. In playing this pivotal role, mucus can also hinder topical delivery of therapeutics to the eye. Recent studies provide evidence that drugs formulated as traditional micro- or nanoparticles are susceptible to entrapment and rapid clearance by ocular mucus. Mucus-penetrating particles (MPPs) is a nanoparticle technology that emerged over the past decade. With a muco-inert surface and a particle size smaller than the mucus mesh size, MPPs can diffuse in ex vivo mucus essentially freely. Preclinical studies have shown that, compared with particles lacking the mucus-penetrating attributes, MPPs can improve the uniformity of drug particle distribution on mucosal surfaces and enhance drug delivery to ocular tissues.

Fraudulent antibiotic products on the market for aquaculture use.

Antibiotics in aquaculture are used to treat bacterial infections. In order for these products to work effectively fish need to be properly dosed. One of the emerging issues in aquaculture is under-dosing large populations of fish with antibiotics. This happens inadvertently for a number of reasons including the use of fraudulent medications. In this study we evaluated 17 antibiotic products (8 florfenicol and 9 oxytetracycline brands purchased in Asia) by HPLC to determine if the product labels accurately reflected the active pharmaceutical ingredient (API) in the package. We determined authenticity scores for different batches of products at two separate laboratories by comparing the observed API to the label API concentration. We found that 48 % of the antibiotic batches had authenticity scores below 80 % (i.e. observed API in package was at least 20 % less than the label API concentration). Further, there were 9 or the 31 batches of drugs tested had no measureable API. Some products had variation in their authenticity scores between batches making it difficult to rely on a brand. The price of florfenicol products may help identify products with low authenticity scores, but in the case of oxytetracycline, the price of all the products tested was relatively similar. The findings in this study suggest that not all florfenicol and oxytetracycline antibiotic products on the market in Asia have API concentrations indicated on their labels. This could be problematic for medicating fish on aquaculture farms.

Topical Triamcinolone Acetonide-Loaded Liposomes as Primary Therapy for Macular Edema Secondary to Branch Retinal Vein Occlusion: A Pilot Study.

Purpose: To explore safety and therapeutic efficacy of a topical ophthalmic triamcinolone acetonide-loaded liposome formulation (TA-LF) as primary therapy in patients with macular edema (ME) secondary to branch retinal vein occlusion (BRVO). Methods: Twelve eyes of 12 patients with ME secondary to BRVO were exposed to a topical instillation of 1 drop of TA-LF (TA 0.2%) 6 times a day for 12 weeks to evaluate safety and efficacy. Best corrected visual acuity (BCVA) intraocular pressure (IOP), slit lamp examination, and central foveal thickness (CFT) were analyzed at every visit. In addition, the morphology of TA-LF was analyzed using scanning electron microscopy (SEM) and transmission electron microscopy (TEM). Results: Patients presented a significant improvement of BCVA and CFT without significant IOP modification (P = 0.94). Treated eyes showed BCVA improvement from 40 ± 12.05 to 64.83 ± 15.97 letters and CFT reduction from 682.91 ± 278.60 to 271.58 ± 57.66 µm after 12 weeks of TA-LF therapy (P < 0.001). No adverse events, including IOP rising, were registered. SEM analysis of liposomal formulations showed that liposome (LP) size depends on its concentration. As the concentration of TA increased, the average size of LPs and the number of larger particles increased as well. TEM study displayed that LP formulation efficiently solubilizes TA crystals in nanoparticles and encapsulates them. Conclusion: LPs can function as nanocarriers of TA and they could be used as topical ophthalmic primary therapy instead of intravitreal drugs in patients with ME secondary to BRVO.

The infection rate of intralesional triamcinolone and the safety of compounding in dermatology for intradermal and subcutaneous injection: A retrospective medical record review.

BACKGROUND: Intralesional injection of sterile medications remains a mainstay in dermatology, enabling a tailored, low-cost, in-office therapy. After the 2012 United States outbreak of fungal meningitis from contaminated intrathecally administered corticosteroids, there has been increased regulation of in-office compounding, regardless of the administration route. Studies demonstrating the safety data of in-office corticosteroid compounding for intradermal or subcutaneous use are lacking. OBJECTIVE: To assess the incidence of infection caused by compounded in-office intralesional triamcinolone. METHODS: A retrospective medical record review identified patients who received in-office intralesional corticosteroid injections in 2016. Medical documentation within 30 days of injection was reviewed for suspected infection. RESULTS: The records of 4370 intralesional triamcinolone injections were assessed, of which 2780 (64%) were compounded triamcinolone with bacteriostatic saline. We identified 11 (0.25%) suspected localized infections, with 4 of the 11 in the compounding cohort. Of these, 7 of 11 occurred after injection of an "inflamed cyst." No hospitalizations or deaths occurred. No temporal or locational relationships were identified. LIMITATIONS: This study was limited to 2 academic institutions. A 30-day postinjection time frame was used. CONCLUSION: In-office compounding for intralesional dermal and subcutaneous administration is safe when sterile products are used by medical practitioners. There is no increased risk of compounded triamcinolone relative to noncompounded triamcinolone.

Bioequivalence Study of 2 Capsule Formulations of Fingolimod 0.5 mg Assessing Both Parent Drug and Active Metabolite in New Zealand Healthy Subjects (Truncated Design).

Fingolimod is indicated for the treatment of patients with the relapsing-remitting form of multiple sclerosis. The primary study objective was to evaluate the bioequivalence of a test formulation, 0.5 mg fingolimod HCl capsule (Lebrina, Asofarma Sociedad Anónima Industrial y Comercial, Argentina) relative to a reference formulation, 0.5 mg fingolimod capsule (Gilenya, Novartis Pharmaceutical, Australia). In a single-center, randomized, single-dose, single-blinded, 2-way crossover study, 33 New Zealand healthy subjects of both sexes were enrolled to receive a 0.5-mg dose of 3 capsules of each fingolimod formulation under fasting conditions, with a 42-day washout period between administrations. Additional pharmacokinetic information regarding its main active metabolite, fingolimod phosphate, was also provided. The point estimate and 90% confidence intervals of the ratios of maximum concentration and area under the plasma concentration-time curve from time 0 to 72 hours were 99.07 (95.83-102.41) and 97.64 (95.33-100.00) for fingolimod, and 95.60 (90.95-100.49) and 98.54 (96.19-100.96), for fingolimod phosphate. Primary parameters, maximum concentration and area under the plasma concentration-time curve from time 0 to 72 hours for fingolimod and fingolimod phosphate were found to have no significant difference when test and reference formulations were compared. Fingolimod and fingolimod phosphate of both formulations were within the accepted 90% confidence interval limits of 80.00% and 125.00%. No significant differences between the test and reference drug products were detected in any of the pharmacokinetic parameters estimated. Notwithstanding the primary conclusion of bioequivalence is focused on the measurement of the parent compound, compliance with the same criteria by the active metabolite reinforces the comparability between the pharmacokinetic profiles of both formulations (ClinicalTrials.gov Identifier: NCT03757338).

Bioequivalence and Bioavailability of an Orodispersible Tablet of Sildenafil Citrate in Healthy Chinese Male Subjects.

Sildenafil citrate is approved to treat erectile dysfunction. An orally disintegrating tablet (ODT) of sildenafil citrate that does not require swallowing or administration with fluids has been developed. The bioequivalence and bioavailability of sildenafil citrate ODT (50 mg) without and with water were compared with conventional sildenafil citrate tablets (50 mg) in an open-label, randomized crossover study. Healthy Chinese male subjects (n = 36) were allocated to 1 of 6 sildenafil citrate treatment sequences under fasted conditions, and plasma samples for determination of sildenafil concentrations were collected predose through 14 hours postdose. Bioequivalence was demonstrated for sildenafil citrate ODT administered without water relative to the sildenafil citrate tablet administered with water; 90%CIs for the ratios of adjusted geometric means for sildenafil AUClast , Cmax , and AUCinf (ratio, 101.41%; 90%CI, 95.49%-107.70%; ratio, 93.55%; 90%CI, 84.15%-104.00%; and ratio, 101.03%; 90%CI, 94.80%-107.66%; respectively) were wholly contained within the bioequivalence acceptance range of 80% to 125%, indicating bioequivalence criteria were met. Relative bioavailability of sildenafil citrate ODT administered with water to the sildenafil citrate tablet (50 mg) administered with water was 97.10%, 91.43%, and 97.09% with respect to sildenafil AUClast , Cmax , and AUCinf , respectively (90%CI, 91.43%-03.12%, 82.25%-101.65%, and 90.90%-103.71%, respectively). Both sildenafil citrate formulations were generally well tolerated in healthy Chinese men. Sildenafil citrate ODT administered without or with water was bioequivalent to or met bioequivalence criteria compared with conventional sildenafil citrate tablets administered with water under fasted conditions in healthy Chinese men, thus offering a convenient alternative method of oral administration.

Pharmacokinetics and Bioequivalence of Clopidogrel Hydrogen Sulfate Tablets in Fed and Fasted Conditions: An Open-Label, Randomized, Semireplicated Crossover Study in Healthy Chinese Volunteers.

Clopidogrel is an antiplatelet drug with high intraindividual variability in systemic exposure and efficacy. It has been used for treating atherosclerosis and acute coronary syndrome and in preventing stent restenosis and thrombotic complications after stent implantation in clinical practice for nearly 20 years. In this study we aimed to evaluate the bioequivalence of 2 clopidogrel hydrogen sulfate formulations (75-mg tablets) under fed (n = 66) and fasted (n = 66) conditions by using the reference-scaled average bioequivalence method. An open-label, randomized, 3-sequence and 3-period crossover (3×3), semireplicated study was designed and conducted. Clopidogrel concentration of plasma samples was measured by high-precision liquid chromatography and tandem mass spectrometry. The pharmacokinetic parameters were derived by a noncompartmental model. In the fed condition the geometric least-squares mean ratios of peak concentration (Cmax ) and area under the concentration-time curve (AUC0-t ) were, respectively, 103.38% and 98.97%, and the corresponding 90%CIs were 95.68% to 111.70% and 94.67% to 103.47%. In the fasted condition the geometric least squares mean ratios of Cmax and AUC0-t were, respectively, 106.53% and 105.77%, and the corresponding 90%CIs were 97.62% to 116.25% and 96.96% to 115.38%. According to the criteria for bioequivalence (80.00% to 125.00%), the test formulations of clopidogrel and Plavix were determined to be bioequivalent.

Knowledge and associated factors towards cytotoxic drug handling among University of Gondar Comprehensive Specialized Hospital health professionals, institutional-based cross-sectional study.

BACKGROUND: Currently, cancer is among the leading causes of morbidity and mortality in the world. Exposure to CDs may occur during drug preparation and mixing, during drug administration, during transport, and cleaning spills and waste disposal. Healthcare workers who prepare or administer antineoplastic drugs, or who work in areas where these drugs are used, can be exposed to these agents. This also affects the public around the exposed area if appropriate disposal system is not known. Several studies reported increased risks of leukemia and breast cancer among nurses handling CDs and not following safety guidelines. Because of the absence of studies in Ethiopia, the current study was conducted to determine the knowledge level of cytotoxic drug handling and associated factors among health professionals in the University of Gondar Comprehensive Specialized Hospital. METHODS: The institutional-based cross-sectional study was conducted from June to August 2019. Epi info 7.1 was used for data entry and then exported into SPSS version 20 for computing, recording, and statistical analysis. Logistic regression was used to explain the relationship with independent variables. RESULTS: Four hundred and twelve health professionals participated in the study with 53.4% males. The participants' mean age was 29.9 (± 5.43) years ranging from 20-60. Two hundred and twenty-three (54.1%) health professionals heard about cytotoxic drugs, and 52.7% (95% UI 47.8-57.8%) had good knowledge of cytotoxic drug handling. Being male sex (AOR = 1.84, 95% CI (1.13-3.00)), age of 29-31 (AOR = 1.99, 95% CI (1.03-3.84)), hearing information about cytotoxic drug handling (AOR = 2.53, 95% CI (1.43-4.47)), ever attended training on cytotoxic drug handling (AOR = 3.15, 95% CI (1.13-8.79)), ever taking courses related to cytotoxic drugs (AOR = 2.03, 95% CI (1.15-3.59)), and good practice (AOR = 3.24, 95% CI (1.95-5.37)) were significantly associated with knowledge towards cytotoxic drug handling. It is therefore imperative to train health professionals and to incorporate CDs handling related course contents while revising curricula to raise the knowledge of health professionals about proper cytotoxic drug handling. CONCLUSION: Above half of the study participants scored higher than the median of the cytotoxic drug handling knowledge questions. Sex, age, information about cytotoxic drug handling, training, taking courses related to cytotoxic drugs, and good practice were significantly associated with knowledge towards cytotoxic drugs handling.

Using immersive simulation to engage student learners in a nonsterile compounding skills laboratory course.

BACKGROUND AND PURPOSE: Although immersive simulation has been applied successfully in multiple pharmacy education settings, none have been used thus far in nonsterile compounding. The objective of this study was to increase student knowledge and confidence when compounding a natural nonsterile product during an immersive simulation. EDUCATIONAL ACTIVITY AND SETTING: The immersive simulation activity was taught over two weeks in a third year advanced nonsterile compounding elective. The first week focused on the extraction of an active ingredient from yarrow, a natural product. The second week immersed the students into an apocalypse simulation to compound a product using the concentrated yarrow extract for a patient who developed a dental infection, using limited resources and supplies. Knowledge and confidence changes were assessed with a pre- and post-assessment. Students' compounded nonsterile products were assessed with the course rubric. Student feedback on the activity was obtained with two open-ended questions. FINDINGS: All 30 students extracted the active ingredient from yarrow leaves and created a unique mouthwash scoring an average (SD) of 8.1 (1) out of 10 points on their graded compounded product. There was a significant increase in the overall knowledge assessment score. All student confidence assessment questions increased on the post-assessment. Student feedback was overwhelmingly positive for the immersive simulation. SUMMARY: An immersive simulation improved students' overall knowledge and confidence in compounding a natural nonsterile product. Schools can utilize a similar approach to teach compounding skills for emergency preparedness.