Anti-infectivity efficacy and pharmacokinetics of WHO recommended single low-dose primaquine in children with acute Plasmodium falciparum in Burkina Faso: study protocol.

BACKGROUND: Primaquine (PQ) has activity against mature P. falciparum gametocytes and proven transmission blocking efficacy (TBE) between humans and mosquitoes. WHO formerly recommended a single transmission blocking dose of 0.75 mg/kg but this was little used. Then in 2012, faced with the emergence of artemisinin-resistant P. falciparum (ARPf) in SE Asia, the WHO recommended a lower dose of 0.25 mg/kg to be added to artemisinin-based combination therapy in falciparum-infected patients in low transmission areas. This dose was considered safe in glucose-6-phosphate dehydrogenase deficiency (G6PDd) and not requiring G6PD testing. Subsequent single low-dose primaquine (SLDPQ) studies have demonstrated safety in different G6PD variants. Dosing remains challenging in children under the age of 5 because of the paucity of PQ pharmacokinetic (PK) data. We plan to assess the anti-infectivity efficacy of SLDPQ using an allometrically scaled, weight-based regimen, with a target dose of 0.25 mg/kg, in children with acute uncomplicated falciparum malaria. METHODS: This study is an open label, randomised 1:1, phase IIb study to assess TBE, tolerability, pharmacokinetics and acceptability of artesunate pyronaridine (ASPYR) administered alone or combined with SLDPQ in 56 Burkinabe children aged ≥ 6 months- < 5 years, with uncomplicated P. falciparum and a haemoglobin (Hb) concentration of ≥ 5 g/dL. We will assess TBE, using direct membrane feeding assays (DMFA), and further investigate PQ pharmacokinetics, adverse events, Hb dynamics, G6PD, sickle cells, thalassaemia and cytochrome 2D6 (CYP2D6) status, acceptability of flavoured PQ [CAST-ClinSearch Acceptability Score Test®], and the population's knowledge, attitude and practices on malaria. EXPECTED RESULTS AND DISCUSSION: We expect children to accept tablets, confirm the TBE and gametocytocidal effects of SLDPQ and then construct a PK infectivity model (including age, sex, baseline Hb, G6PD and CYP2D6 status) to define the dose response TBE relationship that may lead to fine tuning our SLDPQ regimen. Our study will complement others that have examined factors associated with Hb dynamics and PQ PK. It will provide much needed, high-quality evidence of SLDPQ in sick African children and provide reassurance that SLDPQ should be used as a strategy against emerging ARPf in Africa. TRIAL REGISTRATION: ISRCTN16297951. Registered on September 26, 2021.

Ceftolozane/Tazobactam for the Treatment of Complicated Infections in Hospital Settings-A French Real-world Study.

Background: This study describes the conditions of use of ceftolozane/tazobactam (C/T) and associated outcomes in French hospital settings. Methods: This was a prospective, multicenter, French observational study. Patients who received at least 1 dose of C/T were included and followed up as per routine clinical practice, until stop of C/T. Results: A total of 260 patients were enrolled between October 2018 and December 2019 in 30 centers across France. Of these, 177 (68.0%) received C/T as per indication of usage following the results of the antibiogram (documented cases). Among documented patients, the mean age was 61.8 years, 73.4% were males, and 93.8% presented with multidrug-resistant (MDR) bacteria at inclusion. C/T was most frequently prescribed for pneumonia (48.6%), bacteremia (14.7%), complicated intra-abdominal infections (13.0%), or complicated urinary tract infections (9.6%). Pseudomonas aeruginosa was the species most frequently isolated with 212 strains from 155 patients, and 96.2% of these strains were susceptible to C/T. The median duration of C/T treatment was 16.1 days (1-115, n = 176). Complete or partial cure was achieved in 71.7% of patients, C/T was discontinued upon adaptation to microbiology results in 11.3% of patients for the following reasons: treatment failure in 2.8%, death in 4.0%, adverse events in 1.7%, and other in 8.5%. Conclusions: This is the first prospective observational study of C/T utilization in a health care setting enrolling many patients in France. C/T demonstrated a high rate of clinical effectiveness in MDR infections, confirming it as an effective treatment option for complicated infections in a high-risk population.

Association between culture and the preference for, and perceptions of, 11 routes of medicine administration: A survey in 21 countries and regions.

Medicines can be taken by various routes of administration. These can impact the effects and perceptions of medicines. The literature about individuals' preferences for and perceptions of the different routes of administration is sparse, but indicates a potential influence of culture. Our aim was to determine: (i) any association between one's culture and one's preferred route of medicine administration and (ii) individual perceptions of pain, efficacy, speed of action and acceptability when medicines are swallowed or placed in the mouth, under the tongue, in the nose, eye, ear, lungs, rectum, vagina, on the skin, or areinjected. A cross-sectional, questionnaire-based survey of adults was conducted in 21 countries and regions of the world, namely, Tunisia, Ghana, Nigeria, Turkey, Ethiopia, Lebanon, Malta, Brazil, Great Britain, United States, India, Serbia, Romania, Portugal, France, Netherlands, Japan, South Korea, Hong Kong, mainland China and Estonia, using the Inglehart-Welzel cultural map to ensure coverage across all cultures. Participants scored the pain/discomfort, efficacy, speed of onset and acceptability of the different routes of medicine administration and stated their preferred route. Demographic information was collected. A total of 4435 participants took part in the survey. Overall, the oral route was the most preferred route, followed by injection, while the rectal route was the least preferred. While the oral route was the most preferred in all cultures, the percentage of participants selecting this route varied, from 98% in Protestant Europe to 50% in the African-Islamic culture. A multinomial logistic regression model revealed a number of predictors for the preferred route. Injections were favoured in the Baltic, South Asia, Latin America and African-Islamic cultures while dermal administration was favoured in Catholic Europe, Baltic and Latin America cultures. A marked association was found between culture and the preference for, and perceptions of the different routes by which medicines are taken. This applied to even the least favoured routes (vaginal and rectal). Only women were asked about the vaginal route, and our data shows that the vaginal route was slightly more popular than the rectal one.

Dosage Forms Suitability in Pediatrics: Acceptability of Antibiotics in a German Hospital.

Although drug acceptability can have a significant impact on patient adherence in pediatric therapy, data are limited, even for common therapeutic areas. We present the second part of an acceptability study conducted at the University Children's Hospital Düsseldorf, Germany. The study investigated the acceptability of most commonly used antibiotics in a pediatric hospital setting. The researchers used the acceptability reference framework to score the acceptability of five antibiotics based on 150 real-life observer reports of medicine intake. Four antibiotics assessed in this study were formulated as preparations for injection (ampicillin, ampicillin/sulbactam, ceftriaxone, and gentamicin) and one as a powder for oral liquid suspension (co-amoxiclav). All the antibiotics formulated as preparations for injection were rated negatively due to high rates of negative reactions (80%), the use of restraint (51%), the use of extra devices (99%), and long preparation and administration times (100%). The antibiotic formulated as a powder was significantly more well accepted. The study concluded that there is a lack of appropriate formulations for antibiotics for use in children. These findings are important in improving knowledge on acceptability drivers and might help in formulating and prescribing better medicines for children. The study highlights the need for healthcare professionals to have knowledge about the acceptability of different products to select the best-adapted product for each patient.

A Guide to Best Practice in Sensory Analysis of Pharmaceutical Formulations.

It is well established that treatment regime compliance is linked to the acceptability of a pharmaceutical formulation, and hence also to therapeutic outcomes. To that end, acceptability must be assessed during the development of all pharmaceutical products and especially for those intended for paediatric patients. Although acceptability is a multifaceted concept, poor sensory characteristics often contribute to poor patient acceptability. In particular, poor taste is often cited as a major reason for many patients, especially children, to refuse to take their medicine. It is thus important to understand and, as far as possible, optimise the sensory characteristics and, in particular, the taste/flavour/mouthfeel of the formulation throughout the development of the product. Sensory analysis has been widely practiced, providing objective data concerning the sensory aspects of food and cosmetic products. In this paper, we present proposals concerning how the well-established principles of sensory analysis can best be applied to pharmaceutical product development, allowing objective, scientifically valid, sensory data to be obtained safely. We briefly discuss methodologies that may be helpful in reducing the number of samples that may need to be assessed by human volunteers. However, it is only possible to be sure whether or not the sensory characteristics of a pharmaceutical product are non-aversive to potential users by undertaking sensory assessments in human volunteers. Testing is also required during formulation assessment and to ensure that the sensory characteristics remain acceptable throughout the product shelf life. We provide a risk assessment procedure to aid developers to define where studies are low risk, the results of a survey of European regulators on their views concerning such studies, and detailed guidance concerning the types of sensory studies that can be undertaken at each phase of product development, along with guidance about the practicalities of performing such sensory studies. We hope that this guidance will also lead to the development of internationally agreed standards between industry and regulators concerning how these aspects should be measured and assessed throughout the development process and when writing and evaluating regulatory submissions. Finally, we hope that the guidance herein will help formulators as they seek to develop better medicines for all patients and, in particular, paediatric patients.

A review of paediatric injectable drug delivery to inform the study of product acceptability - An introduction.

AIM: The EMA defines acceptability as "the overall ability and willingness of the patient to use, and their caregiver to administer, the medicine as intended" [1]. This paper seeks to outline issues of acceptability in relation to injectable therapy, namely intravenous (IV), intramuscular (IM) and subcutaneous (SC) administration routes, and to lay a foundation to identify a minimum set of data that would satisfy Regulatory Authorities when discussing the acceptability of an injectable product. In addition, it will alert drug product developers to other factors that might contribute to good practice, alternative administration strategies and overall adherence to achieve successful treatment. Whilst the term 'parenteral' means "outside the intestine" [2,3] and so potentially covers a range of administration routes including intranasal and percutaneous administration, this review focuses on IV, IM and SC administration by injection. The use of indwelling canulae or catheters to reduce venepuncture and facilitate prolonged treatment is common and may impact acceptability [4]. This may be influenced by information provided by the manufacturer but is not always in their direct control. Other injectable products suitable for routes such as intradermal, intra-articular, intraosseous and intrathecal, share the requirement to be acceptable but are not specifically covered in this paper [2,5].

Rational and practical considerations to guide a target product profile for patient-centric drug product development with measurable patient outcomes - A proposed roadmap.

The increasing awareness of acceptability and usability of pharmaceutical drug products by the patient as a key quality requirement continues to drive need for integrating patient centric drug product design into the pharmaceutical development process. The complex matrix of multiple drug product related decisions during the early drug development process often limits patient-centric drug product (PCDP) design options in the final commercial drug product development phase. To integrate the specific needs and perspectives of patients into drug development and product design process, a rational approach integrated into the complex development matrix is required from the start and weighs product development decision options accordingly. The aim of this work was to develop a roadmap for PCDP design in a multidisciplinary approach that leads to better usability, adherence and acceptance of the drug by patients via early integration into the development matrix. The proposed rational approach is based upon regulatory requirements and lessons learned from pediatric and geriatric drug development.

Dosage Forms Suitability in Pediatrics: Acceptability of Analgesics and Antipyretics in a German Hospital.

Although medicine acceptability is likely to have a significant impact on the patient's adherence in pediatrics and therefore on therapy success, there is still little data even for common therapeutic areas. For analgesics/antipyretics, healthcare professionals face a wide variety of products and need knowledge to select the best adapted product for each patient. We investigated acceptability of those products most used at the University Children's Hospital Düsseldorf, Germany. Based on 180 real-life observer reports of medicine intake, we used the acceptability reference framework to score acceptability of six distinct medicines. Both ibuprofen and paracetamol tablets, mainly used in adolescents, were positively accepted. This was not the case for the solution for injection of metamizole sodium. Regarding syrups, mainly used in children under 6 years of age, ibuprofen flavored with strawberry and provided with an oral syringe was positively accepted, while paracetamol flavored with orange and provided with a measuring cup was not. Suppository appeared to be an alternative to oral liquids in infants and toddlers with palatability and administration issues. Differences appeared to be driven by dosage forms and formulations. These findings improve knowledge on acceptability drivers and might help formulating and prescribing better medicines for children.

Health technology assessment of paediatric medicines: European landscape, challenges and opportunities inside the conect4children project.

The medicine development process is complex and requires time and effort to ensure safety, efficacy and quality. In paediatrics, this process is even more challenging, as it involves a subgroup of the population that already faces a considerable gap in the clinical evaluation of medicines and devices compared to the adult population. Moreover, access to therapies is heavily influenced by national health technology assessment (HTA) recommendations, which often form the basis for pricing and reimbursement decisions that affect the availability of effective treatments within the national health systems. Yet performing an HTA to assess the relative effectiveness and cost-effectiveness of a new children's treatment has several non-trivial implications, creating a critical issue for the paediatric population. In addition, the advent of innovative health technologies for children emphasises the need to empower the role of HTAs in paediatrics. This article aims at describing the most relevant elements of the drug development process in the paediatric field by focusing on the HTA. Particular attention will be paid to the factors that influence market access for new paediatric medicines and patients' access to treatment. The article will also highlight some central methodological challenges in conducting HTA in the paediatric field. Finally, the article will provide insight into how initiatives, such as conect4children, may subsequently reinforce HTA awareness in the paediatric community and strengthen collaborations through network mechanisms.

Medicine acceptability for older people in hospital and care home: the influence of setting.

OBJECTIVE: Medicines acceptability is likely to have a significant impact on older people's adherence and, consequently, treatment effectiveness. The objective was to explore the influence of setting on medicines acceptability in older people. METHODS: A multi-centre, prospective, cross-sectional, observational study was conducted in one care home and one elderly care hospital ward in London, UK, involving individuals on ≥1 medicine(s) and aged ≥65 years. Data-driven approach was applied using multiple observer-reported outcomes analysis tool to distinguish between positively and negatively accepted medicines. KEY FINDINGS: 263 observer reports from the care home (n = 97) and hospital ward (n = 166) involving 155 distinct medicinal products were assessed. Collectively, medicines appeared better accepted by patients at the hospital. Differences appeared to be driven by variations in solid oral dosage form (SODF) acceptability. Patients with dysphagia poorly accepted medicines in both settings, as expected. SODFs were unexpectedly better accepted in the hospital than in the care home in patients without dysphagia. CONCLUSIONS: Medicines acceptability was affected by patient's characteristics, dosage form type and setting. Changes in care practices between care home and hospital may affect medicine administration and lead to variations in the ability and willingness of patients and carers to use the product as intended.

Proposed Tool to Compare and Assess the Applicability of Taste Assessment Techniques for Pharmaceuticals.

Palatability is amongst the most important determinants of whether or not a child will take a medicine. In order to increase concordance with treatment regimens it is often necessary to utilise a range of formulation techniques to improve the palatability of medicines. These can include selecting a different molecule or version of a molecule (such as a different polymorph or salt form), various taste masking techniques and/or the inclusion of flavours and sweeteners. In order to be able to understand the taste of the Active Pharmaceutical Ingredient (API) and to validate the formulation approach used, it is necessary to be able to use the most reliable taste evaluation method possible. Multiple in vivo and in vitro methods exist nowadays or are proposed in the literature but are often little understood by the pharmaceutical product development community. In particular, different methods may be more relevant at different stages of product development. The aim of this article is to propose a tool to guide the selection of the most appropriate method for the desired evaluation. A spreadsheet-based tool is proposed that is designed to allow the systematic assessment of the applicability of any taste assessment technique existing or new to the users proposed application. A series of criteria are defined that will allow the user to assess the analytical, usability and availability factors for the technique that is being considered. Such a systematic review will help the user to understand the benefits and risks of using each methodology for that application. The use of the tool is illustrated based on currently available data and literature. As new/existing methods are developed/improved, the outcomes of the tool may change.

Acceptability of different oral dosage forms in paediatric patients in hospital setting.

OBJECTIVE: The understanding of acceptability of existing dosage forms is limited in most of the world and hinders the development of acceptable, age-appropriate medicines. The attributes of paediatric medicine acceptability may differ from country to country based on culture, healthcare infrastructure and health policies. This study was designed to map the acceptability of oral medicines in paediatric patients treated in hospital in India. METHODS: An observational, cross-sectional study was conducted in patients aged below 18 years and taking any form of oral medication. Acceptability scores were obtained using CAST-ClinSearch Acceptability Score Test tool. FINDINGS: 490 patients were recruited and 193 evaluations of different pharmaceutical products available in 20 dosage forms and 7 routes of administration were studied. Oral liquids (50%) and tablets (35%) were the most commonly prescribed and administered forms. Regardless of the therapeutic class and age, the oral liquids were 'positively accepted' in infants and toddlers. Acceptability of tablets improved with age and appeared to be generally good from the age of 6. CONCLUSION: This study indicates the limited progress towards adoption of age-appropriate dosage forms in India and thus impact on the acceptability of existing oral dosage forms. The key challenges posed by the adoption of age-appropriate formulations in India are (1) awareness of importance of appropriate administration and acceptability of medicines to children in India, (2) availability of age-appropriate dosage forms and (3) lack of child-appropriate medicine policies.

Exploring Acceptability Drivers of Oral Antibiotics in Children: Findings from an International Observational Study.

Antibiotics are among the most commonly prescribed drugs in children. Adherence to the treatment with these drugs is of the utmost importance to prevent the emergence of resistant bacteria, a global health threat. In children, medicine acceptability is likely to have a significant impact on compliance. Herein we used a multivariate approach, considering simultaneously the many aspects of acceptability to explore the drivers of oral antibiotic acceptability in children under twelve, especially in toddlers and in preschoolers. Based on 628 real-life observer reports of the intake of 133 distinct medicines, the acceptability reference framework highlighted the influence of many factors such as age and sex of patients, previous exposure to treatment, place of administration, administration device, flavor agent in excipients and active pharmaceutical ingredient. These findings from an international observational study emphasize the multidimensional nature of acceptability. Therefore, it is crucial to consider all these different aspects for assessing this multi-faceted concept and designing or prescribing a medicine in order to reach adequate acceptability in the target population.

Real-world evaluation of ceftolozane/tazobactam therapy and clinical outcomes in France.

OBJECTIVES: To describe the real-world clinical use of ceftolozane/tazobactam (C/T) and associated outcomes in France. PATIENTS AND METHODS: Multicenter, prospective cohort study conducted in 22 hospitals. All adult patients who received at least one dose of C/T were asked to participate (2018-2019). Patients were treated according to standard hospital practice and followed up until C/T stop. RESULTS: At the time of the analysis, 84 patients were evaluated. The median age was 64.8 years, and 67.9% (57/84) of patients were males. Fifty-seven patients (57/82, 69.5%) had one or more risk factors for multidrug-resistant (MDR) infections (missing MDR risk factor data for two patients). Most patients were critically ill and had several comorbidities. A majority (59/84, 70.2%) of patients had nosocomial infections. Half of all patients (n=42) had a diagnosis of pneumonia, of which 69% (29/42) were hospital acquired. Overall, 90.5% (76/84) of patients had MDR bacteria. Pseudomonas aeruginosa was the most frequently isolated bacterium (71/80, 88.8%), including 93% (80/86) of C/T-susceptible strains. C/T was prescribed as the first-line treatment to 29.8% (25/84) of patients. A concomitant antibiotic treatment was prescribed to 48.8% (41/84) of patients, of whom 65.9% (27/41) were prescribed concomitant antibiotics at the same time as C/T initiation. Empirical C/T prescription was microbiologically appropriate in 11/16 patients after susceptibility testing. Most patients (44/72, 61.1%) were cured and four (4/72, 5.6%) deaths were reported. CONCLUSIONS: The results showed that C/T was most frequently prescribed for documented cases of P. aeruginosa infections. Most outcomes were positive, including among pneumonia patients.

Adherence and Acceptability of an Oral Antibiotic Used for the Prevention of Pediatric Urinary Tract Infection in Japan.

Urinary tract infection (UTI) is a common health care-associated adverse event and the leading nosocomial complication following pediatric urological surgery. While continuous antimicrobial prophylaxis effectively reduces the risk of UTI following such a surgery, non-adherence is common and represents a distinct clinical entity that is associated with renal scarring. Acceptability is likely to have a significant impact on patient adherence. Herein we used a validated data-driven approach-the ClinSearch acceptability score test (CAST)-to investigate the acceptability of cefaclor, an oral antibiotic widely used for the prevention of pediatric UTI in Japan. Standardized observer reports were collected for 58 intakes of cefaclor 10% fine granules in patients aged from 0 to 17 years. The medicine was classified as positively accepted on the acceptability reference framework. According to the percentage of the prescribed dose taken reported at the end of the treatment, patients exhibited good adherence to this well-accepted medicine. Nonetheless, requirements for greater dosing frequency or poor acceptability in certain patients could affect adherence. Acceptability should be established to ensure patient adherence to medicines used for long-term prophylaxis and consequently guarantee the safety and efficacy of the treatment.

Acceptability of a Sublingual Drug Formulation for Respiratory Tract Infections in Children Aged 3 to 5 Years.

In pediatrics, acceptability has emerged as a key factor for compliance, and consequently for treatment safety and efficacy. Polyvalent mechanical bacterial lysate (PMBL) in 50-mg sublingual tablets is indicated in children and adults for the prophylaxis of recurrent respiratory tract infections. This medication may be prescribed in children over 3 years of age; the appropriateness of this sublingual formulation should thus be demonstrated amongst young children. Using a multivariate approach integrating the many aspects of acceptability, standardized observer reports were collected for medication intake over the course of treatment (days 1, 2, and 10) in 37 patients aged 3 to 5 years, and then analyzed in an intelligible model: the acceptability reference framework. According to this multidimensional model, 50-mg PMBL sublingual tablets were classified as "positively accepted" in children aged 3 to 5 years on all three days of evaluation. As the acceptability evaluation should be relative, we demonstrated that there was no significant difference between the acceptability of these sublingual tablets and a score reflecting the average acceptability of oral/buccal medicines in preschoolers. These results highlight that sublingual formulations could be appropriate for use in preschoolers.

Anticholinergic Activity of Psychotropic Drugs and Cognitive Impairment Among Participants Aged 45 and Over: The CONSTANCES Study.

INTRODUCTION: Psychotropic drugs such as anxiolytics, antidepressants and antipsychotics may have anticholinergic properties that could directly affect patients' cognition. OBJECTIVES: Our objective was to assess the relationship between exposure to anticholinergic-positive (AC+) psychotropic drugs and cognitive impairment compared with psychotropic drugs without anticholinergic activity (AC-). METHODS: This analysis included participants (aged 45-70 years) enrolled between January 2012 and October 2017 in the CONSTANCES cohort treated with psychotropic drugs (antidepressants n = 2602, anxiolytics n = 1195, antipsychotics n = 197) in the 3 years preceding cognitive assessment. Within each drug class, the Anticholinergic Cognitive Burden scale was used to classify drugs as either AC+ or AC-. Cognitive impairment was defined as a score below - 1 standard deviation from the standardized mean of the neuropsychological score. We used multiple logistic regression models and matching on propensity score to estimate the relationship between anticholinergic activity and cognitive impairment. RESULTS: Our analyses did not show any increased risk of cognitive impairment for AC+ antidepressants and anxiolytics, with the exception of a slight increase for AC+ antidepressants in episodic memory (odds ratio [OR] 1.19; 95% confidence interval [CI] 1.05-1.36). Conversely, we found a more marked increase in risk with AC+ antipsychotics on executive function (Trail Making Test-A [TMT-A], OR 4.49 [95% CI 2.59-7.97] and TMT-B, OR 3.62 [95% CI 2.25-5.89]). CONCLUSION: Our results suggest there is no clinically relevant association between the anticholinergic activity of antidepressant and anxiolytic drugs and cognitive impairment in middle-aged adults. An association could exist between AC+ antipsychotics and executive function.

Acceptability of Mebendazole Chewable Tablet in Children Aged 2 to 4 Years in Peru.

Soil-transmitted helminthiasis (STH) is among the most common of parasitic infections, affecting vulnerable populations in tropical/subtropical areas globally. In endemic countries, children, a high-risk population, require treatment and preventive interventions. Mebendazole, a WHO-recommended medicine, originally formulated as a tablet that was often crushed for administration to young children unable to swallow it, was reformulated as a chewable tablet. Acceptability is a key aspect for treatment effectiveness in pediatrics. Herein, we used a validated data-driven approach to investigate the acceptability of the 500-mg mebendazole chewable tablet in children aged 2 to 4 years in Peru. Observer-reported outcomes were collected for 182 medicine intakes. Acceptability was scored using the acceptability reference framework: a three-dimensional map juxtaposing "positively accepted" and "negatively accepted" profiles. Results found that the 500-mg mebendazole chewable tablet was classified as "positively accepted" in children aged 2 to 4 years. Acceptability increased with age and some acceptability issue remain for the younger children. Nevertheless, this formulation was considerably better accepted than the conventional tablets regardless of treatment in young children. This chewable formulation appears to be an appropriate alternative to the hard tablet of mebendazole for treatment of STH and preventive interventions in children aged 2 to 4 years.

Acceptability of generic versus innovator oral medicines: not only a matter of taste.

Optimum use of generic products would require equivalence, not only in terms of quality, safety, and efficacy in clinical studies, but also patient acceptability to not jeopardize treatment success because of non-adherence which would de facto limit the potential cost saving anticipated by their use. Although acceptability is a requirement for the authorization of pediatric innovator products, a survey of European Union (EU) regulatory authorities showed that few have a formal process for assessing patient acceptability of generic products during the registration processes. The current International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) focus on unifying guidance for the development and scrutiny of generics but should include acceptability alongside the other factors being considered for harmonization.

Medicines Acceptability in Hospitalized Children: An Ongoing Need for Age-Appropriate Formulations.

Although knowledge on medicine acceptability remains fragmented, this multi-faceted concept has emerged as a key factor for compliance in pediatrics. In order to investigate the acceptability of medicines used in the University Medical Centre Ibn Sina (CHIS) of Rabat, Morocco, an observational study was conducted. Using a multivariate approach integrating the many aspects of acceptability, standardized observer reports were collected for 570 medicine intakes in patients up to the age of 16, then analyzed on a reference framework. Tablets appeared to be well accepted in children greater than 6 years old, but were crushed/dissolved for 90% of the 40 children aged from 3 to 5, and 100% of the 38 patients younger than 3. Moreover, the prescribed dose was fully taken for only 52% and 16% of these younger children, respectively. Despite this, tablets represented 24% of evaluations in children from 3 to 5 and 20% in infants and toddlers. Oral liquid preparations appeared to be better accepted than tablets in preschoolers, but not for those under 3. Overall, these findings highlight the lack of suitable alternatives for the younger children, especially for formulations of antiepileptics, antithrombotic, and psycholeptic agents in the local context.