scholarly journals Container Closure and Delivery Considerations for Intravitreal Drug Administration

2021 ◽  
Vol 22 (3) ◽  
Author(s):  
Ashwin C. Parenky ◽  
Saurabh Wadhwa ◽  
Hunter H. Chen ◽  
Amardeep S. Bhalla ◽  
Kenneth S. Graham ◽  
...  
Keyword(s):  
Adverse Events ◽  
Product Development ◽  
Drug Product ◽  
Healthcare Providers ◽  
Standard Of Care ◽  
Volume Determination ◽  
Common Procedure ◽  
Drug Products ◽  
Fill Volume ◽  
Container Closure

AbstractIntravitreal (IVT) administration of therapeutics is the standard of care for treatment of back-of-eye disorders. Although a common procedure performed by retinal specialists, IVT administration is associated with unique challenges related to drug product, device and the procedure, which may result in adverse events. Container closure configuration plays a crucial role in maintaining product stability, safety, and efficacy for the intended shelf-life. Careful design of primary container configuration is also important to accurately deliver small volumes (10-100 μL). Over- or under-dosing may lead to undesired adverse events or lack of efficacy resulting in unpredictable and variable clinical responses. IVT drug products have been traditionally presented in glass vials. However, pre-filled syringes offer a more convenient administration option by reducing the number of steps required for dose preparation there by potentially reducing the time demand on the healthcare providers. In addition to primary container selection, product development studies should focus on, among other things, primary container component characterization, material compatibility with the formulation, formulation stability, fill volume determination, extractables/leachables, and terminal sterilization. Ancillary components such as disposable syringes and needles must be carefully selected, and a detailed administration procedure that includes dosing instructions is required to ensure successful administration of the product. Despite significant efforts in improving the drug product and administration procedures, ocular safety concerns such as endophthalmitis, increased intraocular pressure, and presence of silicone floaters have been reported. A systematic review of available literature on container closure and devices for IVT administration can help guide successful product development.

scholarly journals Immunotherapy in hepatocellular carcinoma: evaluation and management of adverse events associated with atezolizumab plus bevacizumab

2021 ◽  
Vol 13 ◽  
pp. 175883592110311
Author(s):  
Chiun Hsu ◽  
Lorenza Rimassa ◽  
Hui-Chuan Sun ◽  
Arndt Vogel ◽  
Ahmed O. Kaseb
Keyword(s):  
Hepatocellular Carcinoma ◽  
Adverse Events ◽  
Kinase Inhibitor ◽  
Treatment Options ◽  
Healthcare Providers ◽  
Safety Data ◽  
Standard Of Care ◽  
Antiangiogenic Agents ◽  
Efficacy And Safety ◽  
First Line

In light of positive efficacy and safety findings from the IMbrave150 trial of atezolizumab plus bevacizumab, this novel combination has become the preferred first-line standard of care for patients with unresectable hepatocellular carcinoma (HCC). Several additional trials are ongoing that combine an immune checkpoint inhibitor with another agent such as a multiple kinase inhibitor or antiangiogenic agent. Therefore, the range of first-line treatment options for unresectable HCC is likely to increase, and healthcare providers need succinct information about the use of such combinations, including their efficacy and key aspects of their safety profiles. Here, we review efficacy and safety data on combination immunotherapies and offer guidance on monitoring and managing adverse events, especially those associated with atezolizumab plus bevacizumab. Because of their underlying liver disease and high likelihood of portal hypertension, patients with unresectable HCC are at particular risk of gastrointestinal bleeding, and this risk may be exacerbated by treatments that include antiangiogenic agents. Healthcare providers also need to be alert to the risks of proteinuria and hypertension, colitis, hepatitis, and reactivation of hepatitis B or C virus infection. They should also be aware of the possibility of rarer but potentially life-threatening adverse events such as pneumonitis and cardiovascular events. Awareness of the risks associated with these therapies and knowledge of adverse event monitoring and management will become increasingly important as the therapeutic range broadens in unresectable HCC.

Determinants of national drug products acceptance across patients, pharmacists, and manufacturers: A mixed method study

2020 ◽  
pp. 174113432092662
Author(s):  
Kawther Khalid Ahmed ◽  
Ali Azeez Al-Jumaili ◽  
Shihab Hattab Mutlak ◽  
Mohammed Kamel Hadi
Keyword(s):  
Mixed Method ◽  
Drug Product ◽  
Healthcare Providers ◽  
Health Sector ◽  
Cross Sectional Study ◽  
Structured Interviews ◽  
Product Price ◽  
Cross Sectional ◽  
Drug Products ◽  
National Drug

Introduction The national pharmaceutical industry is pivotal for both the health sector and the national economy. This study aims to identify determinants of national drug products acceptance. The objectives of this study were to quantitatively measure the level of patient and community pharmacist acceptance of national drug products available in community pharmacies and to qualitatively explore the barriers facing national pharmaceutical companies and investigate the suggested solutions. Methods This cross-sectional study used an explanatory mixed method design. It was conducted in Baghdad, Iraq from July through October 2018. The study included two surveys (one for pharmacy customers and another for pharmacists) and thereafter semi-structured interviews of national pharmaceutical company owners/managers. The interview guide was developed based on preliminary quantitative results. Thematic analysis was used to analyze the interview findings. Results We received 123 patient surveys and 125 usable pharmacist surveys. We conducted seven interviews and stopped when we reached saturation. Integrated qualitative and quantitative findings showed that the main determinants of national drug product acceptance are product characteristics (namely price, packaging, brand, and availability), healthcare providers effect on product promotion and perceived effectiveness, and regulations enforced by authorities mainly the Ministry of Health. Conclusions Product price was the number one modulating factor in patient decision-making when purchasing a drug product. It appears that physicians and pharmacists are playing negative or at least neutral role in promoting national drug products and sustaining patients trust in national drug products. Current policies appeared to slow national drug industry growth and limit manufacturers’ ability to expand their share in the market. Manufacturer marketing efforts can help in gaining physicians and pharmacists support of the national drug product. Reforms to current drug policy and regulations were proposed by manufacturers.

Flexibility in Drug Product Development: A Perspective

2021 ◽  
Author(s):  
Yash Kapoor ◽  
Robert F. Meyer ◽  
Heidi M. Ferguson ◽  
Daniel Skomski ◽  
Pierre Daublain ◽  
...  
Keyword(s):  
Product Development ◽  
Drug Product

scholarly journals High-dose oral and intravenous rifampicin for the treatment of tuberculous meningitis in predominantly HIV-positive Ugandan adults: a phase II open-label randomised controlled trial

2021 ◽  
Author(s):  
Fiona V Cresswell ◽  
David B Meya ◽  
Enock Kagimu ◽  
Daniel Grint ◽  
Lindsey te Brake ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Tuberculous Meningitis ◽  
Geometric Mean ◽  
Standard Of Care ◽  
Hiv Positive ◽  
High Dose ◽  
Open Label ◽  
Dose Oral ◽  
Csf Levels

Abstract Background High-dose rifampicin may improve outcomes of tuberculous meningitis (TBM). Little safety or pharmacokinetic (PK) data exist on high-dose rifampicin in HIV co-infection, and no cerebrospinal fluid (CSF) PK data exist from Africa. We hypothesized that high-dose rifampicin would increase serum and CSF concentrations without excess toxicity. Methods In this phase II open-label trial, Ugandan adults with suspected TBM were randomised to standard-of-care control (PO-10, rifampicin 10mg/kg/day), intravenous rifampicin (IV-20, 20mg/kg/day), or high-dose oral rifampicin (PO-35, 35mg/kg/day). We performed PK sampling on day 2 and 14. The primary outcomes were total exposure (AUC0-24), maximum concentration (Cmax), CSF concentration and grade 3-5 adverse events. Results We enrolled 61 adults, 92% were HIV-positive, median CD4 count was 50cells/µL (IQR 46–56). On day 2, geometric mean plasma AUC0-24hr was 42.9h.mg/L with standard-of-care 10mg/kg dosing, 249h.mg/L for IV-20 and 327h.mg/L for PO-35 (P<0.001). In CSF, standard-of-care achieved undetectable rifampicin concentration in 56% of participants and geometric mean AUC0-24hr 0.27mg/L, compared with 1.74mg/L (95%CI 1.2–2.5) for IV-20 and 2.17mg/L (1.6–2.9) for PO-35 regimens (p<0.001). Achieving CSF concentrations above rifampicin minimal inhibitory concentration (MIC) occurred in 11% (2/18) of standard-of-care, 93% (14/15) of IV-20, and 95% (18/19) of PO-35 participants. Higher serum and CSF levels were sustained at day 14. Adverse events did not differ by dose (p=0.34) Conclusion Current international guidelines result in sub-therapeutic CSF rifampicin concentration for 89% of Ugandan TBM patients. High-dose intravenous and oral rifampicin were safe, and respectively resulted in exposures ~6- and ~8-fold higher than standard-of-care, and CSF levels above the MIC

scholarly journals A Late Dermatologic Presentation of Bullous Pemphigoid Induced by Anti-PD-1 Therapy and Associated with Unexplained Neurological Disorder

2021 ◽  
pp. 861-867
Author(s):  
Xiaoxiao Wang ◽  
Mariano Suppa ◽  
Pascal Bruderer ◽  
Nicolas Sirtaine ◽  
Sandrine Aspeslagh ◽  
...  
Keyword(s):  
Adverse Events ◽  
Bullous Pemphigoid ◽  
Neurological Disorder ◽  
Skin Toxicity ◽  
Standard Of Care ◽  
Immune Checkpoints ◽  
Unusual Association ◽  
Cancer Types ◽  
Favorable Clinical Outcome ◽  
Melanoma Skin

Immunotherapy has become the standard of care for various cancer types. The widespread use of immune checkpoints inhibitors confronts us with a whole range of novel immune-related adverse events. Skin toxicity is one of the most frequent adverse events. In this article, we report a case of anti-PD-1 induced late bullous pemphigoid (BP) with mucosal erosions and associated with a troublesome neurological disorder of undetermined origin in a patient with metastatic melanoma. Skin biopsy was essential to make the diagnosis and rapid initiation of systemic prednisolone played a role in favorable clinical outcome of BP. We will discuss the difficulty of early diagnosis of BP, its unusual association with neurological disorders, and the specific management of this particular dermatological entity.

scholarly journals Randomized phase 2 study of FcRn antagonist efgartigimod in generalized myasthenia gravis

Neurology ◽  
2019 ◽  
Vol 92 (23) ◽  
pp. e2661-e2673 ◽  
Author(s):  
James F. Howard ◽  
Vera Bril ◽  
Ted M. Burns ◽  
Renato Mantegazza ◽  
Malgorzata Bilinska ◽  
...  
Keyword(s):  
Adverse Events ◽  
Myasthenia Gravis ◽  
Vital Signs ◽  
Standard Of Care ◽  
Placebo Treatment ◽  
Phase 2 ◽  
Double Blind ◽  
Severity Scores ◽  
Quality Of Life Scale ◽  
Life Scale

ObjectiveTo investigate safety and explore efficacy of efgartigimod (ARGX-113), an anti-neonatal Fc receptor immunoglobulin G1 Fc fragment, in patients with generalized myasthenia gravis (gMG) with a history of anti-acetylcholine receptor (AChR) autoantibodies, who were on stable standard-of-care myasthenia gravis (MG) treatment.MethodsA phase 2, exploratory, randomized, double-blind, placebo-controlled, 15-center study is described. Eligible patients were randomly assigned (1:1) to receive 4 doses over a 3-week period of either 10 mg/kg IV efgartigimod or matched placebo combined with their standard-of-care therapy. Primary endpoints were safety and tolerability. Secondary endpoints included efficacy (change from baseline to week 11 of Myasthenia Gravis Activities of Daily Living, Quantitative Myasthenia Gravis, and Myasthenia Gravis Composite disease severity scores, and of the revised 15-item Myasthenia Gravis Quality of Life scale), pharmacokinetics, pharmacodynamics, and immunogenicity.ResultsOf the 35 screened patients, 24 were enrolled and randomized: 12 received efgartigimod and 12 placebo. Efgartigimod was well-tolerated in all patients, with no serious or severe adverse events reported, no relevant changes in vital signs or ECG findings observed, and no difference in adverse events between efgartigimod and placebo treatment. All patients treated with efgartigimod showed a rapid decrease in total immunoglobulin G (IgG) and anti-AChR autoantibody levels, and assessment using all 4 efficacy scales consistently demonstrated that 75% showed a rapid and long-lasting disease improvement.ConclusionsEfgartigimod was safe and well-tolerated. The correlation between reduction of levels of pathogenic IgG autoantibodies and disease improvement suggests that reducing pathogenic autoantibodies with efgartigimod may offer an innovative approach to treat MG.Classification of evidenceThis study provides Class I evidence that efgartigimod is safe and well-tolerated in patients with gMG.

Microcannula Utilization for Injectable Facial Fillers: Standard of Care?

2018 ◽  
Vol 35 (4) ◽  
pp. 189-197 ◽  
Author(s):  
Kian Karimi ◽  
Chester F. Griffiths ◽  
Alex Reivitis ◽  
Austin Davis-Hunter ◽  
Elizabeth Zhang ◽  
...  
Keyword(s):  
Adverse Events ◽  
Electronic Medical Records ◽  
Medical Records ◽  
Standard Of Care ◽  
Dermal Filler ◽  
Popular Method ◽  
Patient Reported ◽  
Clinical Series ◽  
Filler Injections

The microcannula technique has become an increasingly popular method for injecting cosmetic fillers. Previous studies have illustrated that the microcannula technique allows filler to be injected with less pain, swelling, and essentially no bruising. This study is a retrospective clinical series examining 247 patients who have undergone dermal filler injections using the microcannula technique from 2011 to 2016 with a single injector, Kian Karimi. The purpose of this study is to assess the frequency of adverse events associated with injections such as bruising and swelling. All 666 recorded patient visits from 2011 to 2016 were analyzed using electronic medical records based on the criteria that the patients had cosmetic filler using the microcannula technique by the surgeon investigator. Of the 666 filler treatments using the microcannula technique, 3 treatments (0.5%) produced adverse events on the day of service, and 32 treatments (4.8%) produced adverse events at 2-week follow-up. In total, 5.4% of treatments produced adverse events. At the 2-week follow-up, 5.7% of treatments using the 25-gauge microcannula produced adverse events ( P = .830); 3.9% of treatments using the 27-gauge microcannula produced adverse events ( P = .612]). Only 3 patients were treated with the 30-gauge microcannula, and 1 patient reported adverse events on the day of service. None of the treatments using the 30-gauge microcannula produced adverse events at the 2-week follow-up ( P = .160). The data support that the microcannula technique is a safe and effective alternative to hypodermic needles for the injection of dermal filler to minimize common adverse events.

scholarly journals Handwash versus hand-rub practices for preventing nosocomial infection in hospital intensive care units: A systematic review and meta-analysis

2020 ◽  
pp. 82-90
Author(s):  
S Bello ◽  
EA Bamgboye ◽  
DT Ajayi ◽  
EN Ossai ◽  
EC Aniwada ◽  
...  
Keyword(s):  
Systematic Review ◽  
Intensive Care ◽  
Adverse Events ◽  
Nosocomial Infection ◽  
Intensive Care Units ◽  
Meta Analysis ◽  
Healthcare Providers ◽  
Length Of Hospital Stay ◽  
Clinical Effectiveness ◽  
Infection Rates

Background: Compliance with handwashing in busy healthcare facilities, such as intensive care units (ICUs), is suboptimal and alcohol hand-rub preparations have been suggested to improve compliance. There is no evidence on the comparative effectiveness between handwash and hand-rub strategies. This systematic review was to assess the effectiveness of handwash versus hand-rub strategies for preventing nosocomial infection in ICUs. Methods Studies conducted in ICUs and indexed in PubMed comparing the clinical effectiveness and adverse events between handwash and hand-rub groups were included in a systematic review. The primary outcome was nosocomial infection rates. Secondary outcomes included microbial counts on healthcare providers’ hands, mortality rates, patient/hospital cost of treatment of healthcare-associated infections (HCAIs), length of ICU/hospital stays, and adverse events. Studies were independently screened and data extracted by at least two authors. Meta-analyses of risk ratios (RR), incidence rate ratios (IRR), odds ratios (OR) and mean differences (MD), were conducted using the RevMan 5.3 software. Results: Seven studies published between 1992-2009 and involving a total of 11,663 patients were included. Five studies (10,981 patients) contributed data to the ICU acquired nosocomial infection rates. The pooled IRR was 0.71 (95% CI 0.61, 0.82; I2 = 94%). On sensitivity analysis, pooled IRR was 0.39 (95% CI 0.32, 0.48; 4 studies; 8,247 patients; I2 = 0%) in favour of hand rub. The pooled OR for mortality was 0.95 (95% CI 0.78, 1.61; 4 studies; 3,475 patients; I2 = 39%). The pooled MD for length of hospital stay was -0.74 (95% CI -2.83, 1.34; 3 studies; 741 patients; I2 = 0%). The pooled OR for an undesirable skin effect was 0.37 (95% CI 0.23, 0.60; 3 studies;1504 patients; I2 = 0%) in favour of hand rub. Overall quality of evidence was low. Conclusion: Hand rub appeared more effective when compared to handwash in ICUs.

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