Tenecteplase use in the management of acute ischemic stroke: Literature review and clinical considerations

Disclaimer In an effort to expedite the publication of articles related to the COVID-19 pandemic, AJHP is posting these manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose Several research articles have been published within the last decade comparing the use of tenecteplase to alteplase in ischemic stroke management. Prior reporting on the comparative therapeutic efficacy and safety profiles of tenecteplase and alteplase is reviewed. Summary Tenecteplase is a variant of native tissue-type plasminogen activator, which rapidly promotes thrombolysis by catalyzing formation of the serine protease plasmin. Tenecteplase has theoretical advantages over alteplase as it has greater fibrin specificity and has a longer half-life than alteplase. This allows the administration of a single bolus over 5 to 10 seconds, as opposed to a bolus followed by a 1-hour infusion with alteplase. While currently approved by the Food and Drug Administration for the treatment of ST-segment elevation myocardial infarction, tenecteplase has also been studied in the treatment of acute ischemic stroke and has extensive data for this off-label indication. The most comprehensive trials to date evaluating the use of tenecteplase in acute ischemic stroke include the TNK-S2B, Australian TNK, ATTEST, Nor-Test, and EXTEND-IA TNK trials. Findings from these randomized controlled studies suggest that tenecteplase is at least as efficacious as alteplase in terms of neurological outcomes. The majority of these studies also reported a trend toward improved safety profiles with the use of tenecteplase. Conclusion Current clinical evidence shows that tenecteplase is not inferior to alteplase for the treatment of ischemic stroke and suggests that tenecteplase may have a superior safety profile. Furthermore, tenecteplase also has practical advantages in terms of its administration. This can potentially lead to a decrease in medication errors and improvement in door to thrombolytic time.

The extent to which off-patent registered prescription medicines are used for off-label indications in Australia: A scoping review

Aim The aim of this scoping review was to determine the extent of off-patent prescription medicine use beyond registered indications in various Australian clinical settings. Method The review followed the Joanna Briggs Institute approach and reported using PRISMA Extension for Scoping Reviews. Online databases were used to identify published literature about off-patent registered prescription medicines used for off-label indications in Australian public hospital, community and primary healthcare settings. In addition, empirical data from the Queensland and the South Australian state-wide medicine formularies were screened for the same medication/off-label indication dyads identified in the literature, and other locally approved uses. Results Overall, fourteen studies were included, conducted in public hospitals (n = 11), palliative care units (n = 2) and the community setting (n = 1). There were 213 reports extracted from the literature describing off-patent registered prescription medicines used for off-label indications, representing 128 unique medication/off-label indication dyads and 32 different medicines. Of these, just five medication/off-label indication dyads were approved for use on both the Queensland and South Australian state-wide medicine formularies, with 12 others only approved for use in Queensland and 16 others only approved for use in South Australia. Further examination of these state-wide formularies demonstrated that the use of off-patent registered prescription medicines beyond registered indications is more extensive than has been reported to date in the literature. There were 28 additional medication/off-label indication dyads approved on the Queensland state-wide medicine formulary and 14 such examples approved for use in South Australia. Of these, just two medication/off-label indication dyads were approved for use on both formularies. Conclusion The extent to which off-patent registered prescription medicines have been repurposed in clinical settings for off-label indications in Australia is greater than previously reported in the literature. Usage and funded availability of certain medication/off-label indication dyads, varies across Australia. These results further expose the two tiered system of medicines regulation in Australia, and its impact on equity of access to medicines. Further research is required to support policy change to encourage submission of registration updates for off-patent prescription medicines.

Where and how to use botulinum toxin on the face and neck – Indications and techniques

Botulinum toxin (BT) is a proteinaceous substance that is derived from the bacterium Clostridium botulinum. It was initially used for the treatment of strabismus by Dr. Alan Scott in the late 1970s after which, it was regularly being used for the cosmetic correction of benign essential blepharospasm by the Carruthers couple. Jean Carruthers while treating one such patient noticed an improvement in the glabellar furrows with an effect on the brow of the patient as well. By the late 1980s through the 1990s, BT was used rampantly as an off-label indication to treat glabellar frown lines. In 2002, the US Food and Drug Administration approved the use of BT type A for the treatment of glabellar furrows. This changed the global scene of facial rejuvenation, heralding a new era. Ever since then, BT has proved to be effective and safe for the treatment of dynamic facial rhytides and is currently being used for various indications. These indications and techniques have evolved with a better understanding of the face and neck musculature and their interactions and actions as well as efficacy of the BT formulations. The authors present an overview of the various cosmetic indications of BT for the face and neck along with the approach to injection techniques for various muscle groups involved.

Pharmacovigilance of the Covid19 therapeutic protocol: Experience of the Hassan II University Hospital of Fez, Morocco and analysis of national and international data

Faced with the pandemic related to the dissemination of the new Coronavirus and the health emergency, Morocco decided to treat patients with Covid-19 with Hydroxychloroquine (HCQ) or Chloroquine (CQ), associated with Azithromycin (AZM) according to a standardized therapeutic scheme, an off-label indication that required pharmacovigilance monitoring to ensure the safety of treated patients. Objective. To present the experience of the Hassan II University Hospital of Fez concerning the management of adverse events of the Covid19 therapeutic protocol. A notification form was made available to the nursing staff to be filled in for any adverse reaction (ADR) observed after the treatment was taken. A daily collection and in-depth analysis was performed. We present the results of the analysis of the data collected in our training between April 21 and August 22, 2020, discussing them with data from national and international databases. 102 ADR cases were collected out of 915 patients hospitalized at the UHC for Covid19 during this period with a prevalence of 11%. 23 patients had underlying defects. The incriminating protocol contained CQ in 55.8% and HCQ in 44.2%. The mean age of the patients was 40.83±17.1 years (18 to 86 years) with a M/F sex ratio of 0.92. The mean time to onset was 3 days (range 1-6 days). The most noted ADRs were digestive, cardiac and neurological. 14 cases were severe (one QT prolongation), 6 of which required transfer to an intensive care unit. The course of action adopted was the restoration of corrective treatment with 12 cases of treatment discontinuation and 8 cases of switching to 2nd line treatment.

Treatment patterns and clinical outcomes with palbociclib-based therapy received in US community oncology practices

Background: Limited studies have evaluated palbociclib-based therapy use in patients with advanced/metastatic breast cancer in the real world. This retrospective study used medical records from US community oncology practices to address the gap. Materials & methods: Eligible patients receiving palbociclib-based therapy per label indication from 3 February 2015 to 31 December 2017 were included. Descriptive analyses were conducted for patient characteristics, treatment patterns and clinical outcomes. Results: The study included 233 patients who received palbociclib + aromatase inhibitor (P+AI) and 48 who received palbociclib + fulvestrant (P+F). Real-world progression-free rate for P+AI was 69.8% (46.8%) at 12 (24) months (P+F: 43.5% [39.9%]) months. Real-world survival rate was 89.8% (71.4%) at 12 (24) months (P+F: 76.3% [65.0%]). Conclusion: The study findings are consistent with previous studies of palbociclib-based therapy.

The WOVEN trial: Wingspan One-year Vascular Events and Neurologic Outcomes

BackgroundPrior studies evaluating the Wingspan stent for treatment of symptomatic intracranial atherosclerotic disease have included patients with a spectrum of both on-label and off-label indications for the stent. The WEAVE trial assessed 152 patients stented with the Wingspan stent strictly by its current on-label indication and found a 2.6% periprocedural stroke and death rate.ObjectiveThis WOVEN study assesses the 1-year follow-up from this cohort.MethodsTwelve of the original 24 sites enrolling patients in the WEAVE trial performed follow-up chart review and imaging analysis up to 1 year after stenting. Assessment of delayed stroke and death was made in 129 patients, as well as vascular imaging follow-up to assess for in-stent re-stenosis.ResultsIn the 1-year follow-up period, seven patients had a stroke (six minor, one major). Subsequent to the periprocedural period, no deaths were recorded in the cohort. Including the four patients who had periprocedural events in the WEAVE study, there were 11 strokes or deaths of the 129 patients (8.5%) at the 1-year follow-up.ConclusionsThe WOVEN study provides the 1-year follow-up on a cohort of 129 patients who were stented according to the current on-label use. It provides a more homogeneous patient group for analysis than prior studies, and demonstrates a relatively low 8.5% 1-year stroke and death rate in stented patients.

Utility of a US Food and Drug Administration (FDA) label indication for condoms for anal sex

Condoms are highly effective for HIV prevention, yet are not currently indicated by the US Food and Drug Administration (FDA) for anal sex. We surveyed a national sample of men who have sex with men to assess whether FDA label indication could affect anticipated condom use, and to determine levels of perceived condom failure for anal sex. We found that 69% of respondents anticipated that a label indication change would increase their likelihood of condom use. Median perceived failure was 15%. We anticipate that these results may aid the FDA in developing standards for a label indication for anal sex.