RTS,S/AS01, a vaccine targeting pre-erythrocytic stages of Plasmodium falciparum

2017 ◽  
Vol 1 (6) ◽  
pp. 533-537
Author(s):  
Lorenz von Seidlein ◽  
Borimas Hanboonkunupakarn ◽  
Podjanee Jittmala ◽  
Sasithon Pukrittayakamee
Keyword(s):  
Protective Efficacy ◽  
Age Groups ◽  
Sub Saharan Africa ◽  
Phase Iii ◽  
European Medicines Agency ◽  
Older Children ◽  
Pivotal Phase ◽  
Malaria Epidemiology ◽  
Maximum Benefit ◽  
Sub Saharan

RTS,S/AS01 is the most advanced vaccine to prevent malaria. It is safe and moderately effective. A large pivotal phase III trial in over 15 000 young children in sub-Saharan Africa completed in 2014 showed that the vaccine could protect around one-third of children (aged 5–17 months) and one-fourth of infants (aged 6–12 weeks) from uncomplicated falciparum malaria. The European Medicines Agency approved licensing and programmatic roll-out of the RTSS vaccine in malaria endemic countries in sub-Saharan Africa. WHO is planning further studies in a large Malaria Vaccine Implementation Programme, in more than 400 000 young African children. With the changing malaria epidemiology in Africa resulting in older children at risk, alternative modes of employment are under evaluation, for example the use of RTS,S/AS01 in older children as part of seasonal malaria prophylaxis. Another strategy is combining mass drug administrations with mass vaccine campaigns for all age groups in regional malaria elimination campaigns. A phase II trial is ongoing to evaluate the safety and immunogenicity of the RTSS in combination with antimalarial drugs in Thailand. Such novel approaches aim to extract the maximum benefit from the well-documented, short-lasting protective efficacy of RTS,S/AS01.

Wie sicher sind pädiatrische Arzneimittelverordnungen?

2007 ◽  
Vol 7 (06) ◽  
pp. 345-350 ◽  
Author(s):  
Martin Grimm ◽  
Corinna Gebauer ◽  
Thomas Kapellen ◽  
Oana Brosteanu ◽  
Wieland Kiess
Keyword(s):  
Vitamin K ◽  
European Medicines Agency ◽  
Off Label

ZusammenfassungHintergrund: Viele pädiatrisch eingesetzte Arzneimittel sind für Kinder nicht zugelassen. Der Mangel an Informationen zu Anwendung und Nebenwirkungen ist in der Frühgeborenen- und Intensivmedizin besonders hoch.Ziel: Das Ziel bestand in der Untersuchung des Zulassungsstatus der Medikamentenverordnungen an einer universitären Kinderklinik zur Priorisierung und Planung von Arzneimittelstudien.Material und Methoden: Auf einer interdisziplinären, einer neonatologischen Intensivstation und einer allgemeinpädiatrischen Station wurden über einen Zeitraum von 3 Monaten alle Arzneimittelverordnungen erfasst. Zur Analyse des Zulassungsstatus dienten die „Rote Liste®” und die Fachinformationen.Ergebnisse: 377 Patienten erhielten 2486 Verordnungen. Die häufigsten Arzneimittel waren Paracetamol, Vitamin K und Acetylcystein (ACC). Unlizensiert waren 5,5% aller Verordnungen; 39,5% wurden außerhalb der Altersgrenzen, 16,7% mit nicht zugelassener Indikation angewendet.Schlussfolgerung: Die unlizensierte und Off-Label-Arzneimittelanwendung ist noch weit verbreitet. Durch systematische Analysen können in Zusammenarbeit mit EMEA (European Medicines Agency) und PAED-Net Prioritätenlisten für Studien erstellt werden, die die Arzneimittelsicherheit erhöhen.

Alternativas farmacéuticas: ¿pueden ser intercambiables?

2020 ◽  
Vol 2 (2) ◽  
pp. 38-42
Author(s):  
Miriam del Carmen Carrasco-Portugal ◽  
Francisco Javier Flores-Murrieta
Keyword(s):  
Generic Substitution ◽  
In Vivo Studies ◽  
Regulatory Agencies ◽  
European Medicines Agency ◽  
Reference Formulation ◽  
Active Moiety ◽  
Significant Difference ◽  
Pharmaceutical Form ◽  
Extent Of Absorption

Pharmaceutical alternatives are products with the same active moiety, but different salt, ester or pharmaceutical form. Regulatory agencies have different criteria for this kind of drug. The European Medicines Agency (EMA) accepts the generic substitution using these alternatives, whereas the Food and Drug Administration (FDA) only authorizes generic substitution of pharmaceutical equivalents. The objective of this paper is to describe some relevant aspects that should be considered before deciding on making a generic substitution with pharmaceutical alternatives. It is important to note that a pharmaceutical alternative must show no significant difference in the rate and extent of absorption (bioequivalence) in a well-conducted in vivo study when compared with the reference formulation. Current Mexican regulations state that generic substitution is possible using pharmaceutical alternatives when bioequivalence is demonstrated in in vivo studies conducted under the NOM-177-SSA1-2013 criteria. In conclusion, generic substitution with pharmaceutical alternatives is possible if these products demonstrate in vivo bioequivalence when compared with the reference product.

Biosimilars of Adalimumab in Inflammatory Bowel Disease: Are we Ready for that?

2019 ◽  
Vol 25 (1) ◽  
pp. 7-12 ◽  
Author(s):  
Marjorie Argollo ◽  
Gionata Fiorino ◽  
Daniela Gilardi ◽  
Federica Furfaro ◽  
Giulia Roda ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Health Care Providers ◽  
Bowel Disease ◽  
Biological Treatment ◽  
Reference Product ◽  
European Medicines Agency ◽  
Care Providers ◽  
Inflammatory Bowel ◽  
To Receive ◽  
The Ideal

Introduction: Biosimilars present a considerable potential to reduce costs related to clinical management allowing health-care providers to reinvest this money, leading to a wider access to an effective biological treatment with monoclonal antibodies (mAb). Infliximab biosimilars have already been incorporated in daily clinical practice and are currently used in all indications for which the reference product (RP) was approved. Areas covered: In the next few years, also adalimumab biosimilars will become available for the treatment of inflammatory bowel disease (IBD). In fact, several of them (ABP501, BI 695501, GP2017, and SB5) have been approved by the European Medicines Agency (EMA) with the same indications of the reference product (Humira ®). Initial preclinical data proved a strong similarity between all biosimilars and the RP. Moreover, phase 3 studies in rheumatoid arthritis and psoriasis showed no differences in terms of efficacy, safety, and immunogenicity. Data on IBD patients are urgently needed. Expert opinion: Biosimilars of adalimumab showed equivalent clinical efficacy to the RP in other immunemediated diseases. However, defining the ideal patient’s profile to receive or to be switched to a biosimilar, choosing one biosimilar vs. another, or cross-switching among biosimilars, will become the next challenge in IBD.

Do the Natural Chemical Compounds Interact with the Same Targets of Current Pharmacotherapy for Weight Management?-A Review

2019 ◽  
Vol 20 (4) ◽  
pp. 399-411 ◽  
Author(s):  
Shiqi Luo ◽  
George Binh Lenon ◽  
Harsharn Gill ◽  
Heidi Yuen ◽  
Angela Wei Hong Yang ◽  
...  
Keyword(s):  
Weight Loss ◽  
Weight Management ◽  
Pancreatic Lipase ◽  
Weight Reduction ◽  
Chemical Compounds ◽  
Alpha Amylase ◽  
Melanocortin Receptor ◽  
Health Concern ◽  
European Medicines Agency ◽  
Ppar Γ

Background: Obesity has become a worldwide health concern. Pharmacotherapies are now being introduced because lifestyle modifications alone are insufficient for weight management. The treatment outcomes of current approved anti-obesity agents are not satisfying due to drug-related intolerances. And so natural therapies including herbal medicines are popular alternatives for weight reduction; however, there are limited studies about their mechanism of actions. Methods: Five databases (PubMed, Scopus, Google Scholar, Science Direct, Proquest) were searched to investigate the targets and safety profiles of the current and past anti-obesity drugs that have been approved by the Food and Drug Administration (FDA) or the European Medicines Agency (EMA) as well as the commonly used off-label agents. The targets for weight-loss natural products and their principle bioactive components have also been searched. Only articles in English were included. Results: The targets for current anti-obesity single agents include pancreatic lipase, Glucagon Like Peptide-1(GLP-1) receptor, and serotonin 2C (5-HT2C) receptor. Potential targets such as amylin, pancreatic alpha amylase, leptin receptor, melanocortin receptor 4 receptor (MC4R), Peroxisome Proliferator- Activated Receptors gamma (PPAR γ), endocannabinoid 1 (CB1) receptor and Adenosine Monophosphate (AMP)-Activated Protein Kinase (AMPK) were discussed in various studies. Natural compounds have been found to interact with targets like pancreatic lipase, pancreatic alpha amylase, AMPK and PPAR γ to achieve weight reduction. Conclusion: Current pharmacotherapies and natural chemical compounds do act on same targets. Further investigations on the interactions between herbal compounds and the above targets are essential for the development of novel weight-loss therapies.

scholarly journals Recent advances in understanding NRF2 as a druggable target: development of pro-electrophilic and non-covalent NRF2 activators to overcome systemic side effects of electrophilic drugs like dimethyl fumarate

F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 2138 ◽  
Author(s):  
Takumi Satoh ◽  
Stuart Lipton
Keyword(s):  
Side Effects ◽  
Specific Interaction ◽  
Dimethyl Fumarate ◽  
Carnosic Acid ◽  
European Medicines Agency ◽  
Related Factor ◽  
Inflammatory Phase ◽  
First Case ◽  
Systemic Side Effects ◽  
Transcriptional Pathway

Dimethyl fumarate (DMF) is an electrophilic compound previously called BG-12 and marketed under the name Tecfidera®. It was approved in 2013 by the US Food and Drug Administration and the European Medicines Agency for the treatment of relapsing multiple sclerosis. One mechanism of action of DMF is stimulation of the nuclear factor erythroid 2-related factor 2 (NRF2) transcriptional pathway that induces anti-oxidant and anti-inflammatory phase II enzymes to prevent chronic neurodegeneration. However, electrophiles such as DMF also produce severe systemic side effects, in part due to non-specific S-alkylation of cysteine thiols and resulting depletion of glutathione. This mini-review presents the present status and future strategy for NRF2 activators designed to avoid these side effects. Two modes of chemical reaction leading to NRF2 activation are considered here. The first mode is S-alkylation (covalent reaction) of thiols in Kelch-like ECH-associated protein 1 (KEAP1), which interacts with NRF2. The second mechanism involves non-covalent pharmacological inhibition of protein-protein interactions, in particular domain-specific interaction between NRF2 and KEAP1 or other repressor proteins involved in this transcriptional pathway. There have been significant advances in drug development using both of these mechanisms that can potentially avoid the systemic side effects of electrophilic compounds. In the first case concerning covalent reaction with KEAP1, monomethyl fumarate and monoethyl fumarate appear to represent safer derivatives of DMF. In a second approach, pro-electrophilic drugs, such as carnosic acid from the herb Rosmarinus officinalis, can be used as a safe pro-drug of an electrophilic compound. Concerning non-covalent activation of NRF2, drugs are being developed that interfere with the direct interaction of KEAP1-NRF2 or inhibit BTB domain and CNC homolog 1 (BACH1), which is a transcriptional repressor of the promoter where NRF2 binds.

scholarly journals Thrombocytopenia and Intracranial Venous Sinus Thrombosis after “COVID-19 Vaccine AstraZeneca” Exposure

2021 ◽  
Vol 10 (8) ◽  
pp. 1599
Author(s):  
Marc E. Wolf ◽  
Beate Luz ◽  
Ludwig Niehaus ◽  
Pervinder Bhogal ◽  
Hansjörg Bäzner ◽  
...  
Keyword(s):  
Sinus Thrombosis ◽  
Clinical Manifestations ◽  
Venous Sinus ◽  
European Medicines Agency ◽  
Coagulation Disorder ◽  
Platelet Factor ◽  
Venous Sinus Thrombosis ◽  
Antiplatelet Antibodies ◽  
Imaging Results ◽  
Venous Thromboembolic Events

Background: As of 8 April 2021, a total of 2.9 million people have died with or from the coronavirus infection causing COVID-19 (Corona Virus Disease 2019). On 29 January 2021, the European Medicines Agency (EMA) approved a COVID-19 vaccine developed by Oxford University and AstraZeneca (AZD1222, ChAdOx1 nCoV-19, COVID-19 vaccine AstraZeneca, Vaxzevria, Covishield). While the vaccine prevents severe course of and death from COVID-19, the observation of pulmonary, abdominal, and intracranial venous thromboembolic events has raised concerns. Objective: To describe the clinical manifestations and the concerning management of patients with cranial venous sinus thrombosis following first exposure to the “COVID-19 vaccine AstraZeneca”. Methods: Patient files, laboratory findings, and diagnostic imaging results, and endovascular interventions of three concerning patients were evaluated in retrospect. Results: Three women with intracranial venous sinus thrombosis after their first vaccination with “COVID-19 vaccine AstraZeneca” were encountered. Patient #1 was 22 years old and developed headaches four days after the vaccination. On day 7, she experienced a generalized epileptic seizure. Patient #2 was 46 years old. She presented with severe headaches, hemianopia to the right, and mild aphasia 13 days after the vaccination. MRI showed a left occipital intracerebral hemorrhage. Patient #3 was 36 years old and presented 17 days after the vaccination with acute somnolence and right-hand hemiparesis. The three patients were diagnosed with extensive venous sinus thrombosis. They were managed by heparinization and endovascular recanalization of their venous sinuses. They shared similar findings: elevated levels of D-dimers, platelet factor 4 antiplatelet antibodies, corona spike protein antibodies, combined with thrombocytopenia. Under treatment with low-molecular-weight heparin, platelet counts normalized within several days. Conclusion: Early observations insinuate that the exposure to the “COVID-19 vaccine AstraZeneca” might trigger the expression of antiplatelet antibodies, resulting in a condition with thrombocytopenia and venous thrombotic events (e.g., intracranial venous sinus thrombosis). These patients’ treatment should address the thrombo-embolic manifestations, the coagulation disorder, and the underlying immunological phenomena.

Sign in / Sign up

Export Citation Format

Share Document