Removing barriers to accessing medical cannabis for paediatric patients.

Medical cannabis (MC) may offer therapeutic benefits for children with complex neurological conditions and chronic diseases. In Canada, parents, and caregivers frequently report encountering barriers when accessing MC for their children. These include negative preconceived notions about risks and benefits, challenges connecting with a knowledgeable healthcare provider (HCP), the high cost of MC products, and navigating MC product shortages. In this manuscript, we explore several of these barriers and provide recommendations to decision-makers to enable a family-centered and evidence-based approach to MC medicine and research for children.

From paediatric formulations development to access: Advances made and remaining challenges.

Developing suitable paediatric formulations and ensuring access to them by the greatest number of the 2.2 billion children worldwide are equally important to provide optimal pharmacotherapy. This review focuses on the progress made over the last two decades with paediatric oral formulations with respect to evidence for acceptability and dosing flexibility of liquid and solid oral dosage forms. It also discusses the clinical needs for, and the access to, paediatric formulations for existing authorised medicines. A significant body of new knowledge now supports the acceptability of solid oral dosage forms in children, resulting in an increasing number of medicines commercialised as multiparticulates, including minitablets that are starting to be brought to market. However, there are gaps with these formulations that deserve more research. Even though efforts have been made to identify medicines in need of age-appropriate formulations, there is no common priority list shared internationally. Such prioritisation would help to develop paediatric formulations with the greatest potential for providing a health benefit to children worldwide. In addition, available data highlight that paediatric formulation access is fragmented and unequal, with commercialisation of suitable paediatric formulations too often limited to some countries/regions. We propose actions to better align decisions during the development of paediatric formulations and promote a more globalised approach to facilitate registration pathways between different jurisdictions. Furthermore, discussions about alignment between approval, pricing and reimbursement processes should also happen, leaving working in siloes behind us. It is time for adults to start thinking outside the box for children.

Topical nitroglycerin ointment as salvage therapy for peripheral tissue ischemia in newborns: a systematic review.

BACKGROUND: Topical nitroglycerin (TNG) ointment has been used for almost 3 decades to treat neonatal peripheral tissue ischemia, but this product is now no longer being produced by its Canadian manufacturer. Our aim was to investigate the efficacy and safety of TNG products in newborns in neonatal intensive care units. METHODS: In this systematic review we searched Embase, CINAHL, MEDLINE, PubMed and Web of Science from inception to April 2020 for studies on the use of TNG products (TNG ointment, TNG spray, glyceryl trinitrate [GTN] patch) for the treatment of neonatal tissue ischemia. We did not apply language or study design limitations. Animal studies and duplicate records were excluded. Two reviewers screened and extracted data. The Tool for Evaluating the Methodological Quality of Case Reports and Case Series was used to assess the risk of bias of individual studies. RESULTS: We included 23 articles (20 case reports, 2 case series and 1 retrospective audit) describing the use of TNG ointment, TNG spray or GTN patch in the treatment of 39 tissue ischemia events in 37 newborns. Twenty-three (62.2%), 12 (32.4%), 1 (2.7%) and 1 (2.7%) infants received TNG ointment, GTN patch, both TNG ointment and GTN patch, and TNG spray, respectively. Nineteen (76.0%) and 7 (53.8%) injuries treated with TNG ointment and GTN patch showed complete recovery, respectively. Two (16.7%) infants treated with GTN patch experienced adverse events (i.e., methemoglobinemia) requiring treatment discontinuation. INTERPRETATION: TNG ointment presents a safe therapeutic modality for salvage therapy of neonatal tissue ischemia. Engagement of stakeholders is essential to address its recent commercial inaccessibility in Canada.

Providing Suitable Pediatric Formulations for Canadian Children: A Call for Action.

BACKGROUND: Many medications given to children have no commercially available, age-appropriate formulations. This leads to manipulation of dosage forms designed for adults (compounding), which can result in an increased risk of dosing errors and adverse events, lack of medication adherence because of taste issues, and suboptimal dosing with therapeutic failure. OBJECTIVES: To determine which drugs required compounding for oral administration to children in a Canadian hospital and, for each compounded drug, to determine whether it was available as licensed oral pediatric formulations in the United States or the European Union. METHODS: Drugs requiring compounded liquid formulations for oral administration, dispensed from January 1 to December 31, 2015, at a Canadian university-affiliated tertiary pediatric hospital, and prepared in a quantity exceeding 0.5 L per year, were retrospectively identified. The online drug databases of Health Canada, the US Food and Drug Administration, the European Medicines Agency (EMA), and the UK Medicines and Healthcare Products Regulatory Agency were searched to determine the availability of child-friendly oral formulations for these drugs. The regulatory status in each jurisdiction was also compared. For licensed formulations with potential concerns about excipient safety, EMA guidelines for sorbitol, propylene glycol, ethanol, and sodium benzoate were used to determine pediatric suitability. RESULTS: Of the 56 compounded drugs investigated, 27 (48%) had a suitable commercialized child-friendly formulation available outside Canada. Overall, these drugs had been on the Canadian market for a median of 35 years, and almost half (27 [48%]) had a pediatric indication in Canada. CONCLUSIONS: Canada is lagging behind the United States and the European Union in ensuring availability of and access to suitable pediatric formulations. Potential explanations for this gap include small market size, regulatory uncertainties, and reimbursement shortcomings. Steps must be taken to implement pediatric-sensitive regulations and incentives, as well as reimbursement policies, to address these unmet needs.

CONTEXTE: Plusieurs médicaments administrés aux enfants ne sont pas disponibles commercialement sous une forme pharmaceutique adaptée à leur âge. Ceci entraîne une manipulation des formes destinées aux adultes (préparation magistrale) et peut conduire à une augmentation du risque d'erreurs de dosage et d'effets indésirables, un manque d'observance médicamenteuse secondairement à des problèmes de goût, et un dosage sous-optimal associé à des échecs thérapeutiques. OBJECTIFS: Définir les médicaments qui exigent une préparation magistrale pour être administrés par voie orale aux enfants dans un hôpital canadien et, pour chaque médicament faisant l'objet d'une préparation magistrale, déterminer s'il est disponible sous une forme pharmaceutique orale autorisée pour les enfants aux États-Unis ou dans l'Union européene. MÉTHODES: Les médicaments nécessitant des préparations magistrales liquides pour administration orale, distribués entre le 1er janvier et le 31 décembre 2015 dans un hôpital de soins pédiatriques tertiaires affilié à une université canadienne et dont la quantité préparée était supérieure à 0.5 L par an, ont été déterminés rétrospectivement. Les bases de données en ligne de médicaments de Santé Canada, de la Food and Drug Administration américaine, de l'Agence européenne des médicaments (AEM) et de la Medicines and Healthcare Products Regulatory Agency (Royaume-Uni) ont été interrogées pour déterminer la disponibilité de formes pharmaceutiques orales adaptées aux enfants pour ces médicaments. Le statut réglementaire de chaque pays a également fait l'objet d'une comparaison. Pour les formes pharmaceutiques autorisées présentant des problèmes potentiels d'innocuité des excipients, les directives de l'AEM concernant le sorbitol, le propylène glycol, l'éthanol et le benzoate de sodium ont servi à déterminer si un usage pédiatrique était acceptable. RÉSULTATS: Des 56 médicaments étudiés faisant l'objet d'une préparation magistrale, 27 (48 %) avaient une forme pharmaceutique commercialisée adaptée aux enfants en dehors du Canada. Au total, ces médicaments sont sur le marché canadien depuis une médiane de 35 ans et près de la moitié (27 [48 %]) ont une indication pédiatrique au Canada. CONCLUSIONS: Le Canada accuse un retard par rapport aux États-Unis et à l'Union européenne quant à la disponibilité et à l'accès à des formes pharmaceutiques adéquates pour les enfants. La petite taille du marché, les incertitudes en matière réglementaire et les lacunes concernant le remboursement pourraient notamment expliquer cet écart. Il est nécessaire de prendre des mesures pour mettre en place des réglementations et des incitatifs ainsi que des politiques de remboursement axés sur les enfants pour répondre à ces besoins criants.

Pediatric drug data in Canadian drug monographs: a descriptive analysis.

BACKGROUND: Optimal drug therapy in children relies on the availability of pediatric-specific information. We aimed to describe the current status of pediatric pharmacotherapy data in monographs of new drugs approved by Health Canada. METHODS: In this descriptive analysis, we reviewed the quality and quantity of monographs of new drugs approved by Health Canada between Jan. 1, 2007, and Dec. 31, 2016. We excluded drugs withdrawn from the Canadian market and drugs with primary indications irrelevant to pediatrics. We determined the percentage of included drug monographs that listed pediatric-specific information. RESULTS: During this study period, Health Canada approved 281 drugs, 270 of which met our inclusion criteria. Pediatric-specific information and indication were present in 127 (47.1%) and 75 (27.8%) of the drug monographs, respectively. Of all pediatric age groups, neonates had the lowest number of indications listed in the product monographs (7, 2.6%). Only 9 (60%) oral drugs indicated for children 6 years of age or younger were available in child-friendly, age-appropriate dosage forms. INTERPRETATION: Most of the new drugs approved by Health Canada do not contain pediatric or neonatal indications in their product monographs, and therefore, are used "off-label." Regulatory mechanisms are required to promote both neonatal and pediatric drug development and submission of available pediatric data by manufacturers to Health Canada.

Pharmacare in Canada: The paediatric perspective.

Canada's drug insurance system is one of the most expensive in the world, yet millions of Canadians still struggle to access necessary medications. As a result, provincial, territorial, and federal governments are considering public pharmacare policy proposals to ensure that all Canadians can access the medications they need. Pharmacare policies offer an opportunity to prioritize children and youth, whose unique drug needs have long been neglected. Prescription drug use is common in this population, with approximately half of Canadian children and youth requiring at least one prescription in any given year. Drug use remains concentrated, however, among those with complex, chronic, and serious diseases. Children and youth rely heavily on compounded and off-label prescription drugs, which impacts safety, efficacy, palatability, and cost. Reimbursement decision-making bodies do not appropriately value the unique benefits of paediatric drugs, including child-friendly formulations, improved quality of life for children and families, and cost-savings outside the healthcare system. Regardless of the pharmacare model ultimately implemented, ensuring universal, comprehensive, and portable prescription drug coverage for all children and youth is essential. To accomplish this, paediatric drug experts should develop a national, evidence-informed formulary of paediatric drugs. Health Canada should also improve processes to make commercial paediatric drugs and child-friendly formulations more available and accessible. The federal government must also support paediatric drug research and development to this end.