Prescription switching: Rationales and risks

Kirby, Michael; Allchorne, Paula; Appanna, Tim; Davey, Patrick; Gledhill, R. F.; Green, James S. A.; Greene, Damian; Rosario, Derek J.

doi:10.1111/ijcp.13429

Cited by 6 publications

(6 citation statements)

References 76 publications

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“…Most patients switched either within the first 3 months of first-line treatment or after 12 months, and most switched to leuprorelin or triptorelin. Therapeutic drug switching does occur and may be done for convenience, to reduce cost or to reduce side effects [47]. However, while there is some evidence of clinical benefit in switching a patient from a GnRH agonist to an antagonist [48] there is limited evidence for the opposite approach with no established protocols for switching between these different classes of drug [47].…”

Section: Discussionmentioning

confidence: 99%

“…Therapeutic drug switching does occur and may be done for convenience, to reduce cost or to reduce side effects [47]. However, while there is some evidence of clinical benefit in switching a patient from a GnRH agonist to an antagonist [48] there is limited evidence for the opposite approach with no established protocols for switching between these different classes of drug [47]. Further, with real-world evidence studies showing mean time to CV event beyond 1-year [36], long-term treatment on an antagonist may be required to reduce CV risk.…”

Section: Discussionmentioning

confidence: 99%

“…A major limitation was the small sample size of degarelix-treated patients, which prevented subgroup analysis of individual risk factors. The small sample size is common to other retrospective analyses of degarelix, with the low number of patients taking degarelix possibly due to clinicians favouring GnRH agonists as first-line treatments [42,47]. Further, events of hypertension, stroke, and CV death were not included in the analysis.…”

Section: Study Limitationsmentioning

confidence: 99%

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Cardiovascular risk profiles of GnRH agonists and antagonists: real-world analysis from UK general practice

Davey

Kirby

2020

World J Urol

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Purpose Androgen deprivation therapy (ADT) is the mainstay for the management of metastatic prostate cancer. Available pharmaceutical ADTs include gonadotropin-releasing hormone (GnRH) agonists and antagonists. Here, real-world data are presented from the UK general practitioner Optimum Patient Care Research Database. The study investigated the hypothesis that GnRH antagonists have lower cardiac event rates than GnRH agonists. Methods The incidence of cardiac events following initiation of GnRH antagonist or agonist therapy was investigated in a population-based cohort study conducted in UK primary care between 2010 and 2017. Results Analysis of real-world data from the UK primary care setting showed that relative risk of experiencing cardiac events was significantly lower with degarelix, a GnRH antagonist, compared with GnRH agonists (risk ratio: 0.39 [95% confidence interval 0.191, 0.799]; p = 0.01). Patients that received degarelix as first-line treatment switched treatment more frequently (33.7%), often to a GnRH agonist, than those who initiated treatment with a GnRH agonist (6.7–18.6%). Conclusion Screening for known or underlying vascular disease and identifying those at high risk of a cardiac event is important for risk mitigation in patients with prostate cancer receiving hormone therapy. The GnRH antagonist degarelix conferred a significantly lower risk of cardiac events than GnRH agonists. Prior to treatment, patients should be stratified based on level of cardiovascular (CV) risk, and appropriate lifestyle, and pharmacological interventions to mitigate CV risk should be recommended. CV risk factors and patient response to the intervention should be monitored at regular intervals.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Study Limitationsmentioning

confidence: 99%

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Cardiovascular risk profiles of GnRH agonists and antagonists: real-world analysis from UK general practice

Davey

Kirby

2020

World J Urol

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“…A plethora of statins now exist with varying pharmacological properties [7][8][9]. Lipophilic prodrug statins, such as lovastatin and simvastatin, become activated when metabolized in the liver, the primary site of de novo cholesterol synthesis [10].…”

mentioning

confidence: 99%

Targeting the Mevalonate Pathway in Cancer

Juarez

Fruman

2021

Trends in Cancer

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“…Multiple‐drug resistance (MDR) in prostate cancer has become a severe problem owing to limited available targeted agents. The majority of the resistance is due to resurgence of the androgen receptor (AR) signaling, which is a primary culprit for therapeutic failure in incurable prostate cancers (PCa), especially in castration‐resistant PCa (CRPC) . First‐line AR‐directed therapies (ADTs; e.g., enzalutamide (Xtandi®) and abiraterone (Zytiga®)) depend on the druggability of the AR ligand binding domain (LBD); however, relapses emerge when affinity‐related mutations (e.g., AR T877A in LNCaP) or complete loss of LBD (known as AR variants; e.g., AR V7 in 22Rv1) occur (models used in this study are listed in Table ), which leads to MDR.…”

Section: Ic50 [μM][a] Of 1–4 and Derivatives 22 A And 22 B With The Cmentioning

confidence: 99%

Affinity‐Driven Covalent Modulator of the Glyceraldehyde‐3‐Phosphate Dehydrogenase (GAPDH) Cascade

Chern

Fang

et al. 2018

Angew Chem Int Ed

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Traditional medicines provide a fertile ground to explore potent lead compounds, yet their transformation into modern drugs is fraught with challenges in deciphering the target that is mechanistically valid for its biological activity. Herein we reveal that (Z)-(+)-isochaihulactone (1) exhibited significant inhibition against multiple-drug-resistant (MDR) cancer cell lines and mice xenografts. NMR spectroscopy showed that 1 resisted an off-target thiolate, thus indicating that 1 was a target covalent inhibitor (TCI). By identifying the pharmacophore of 1 (α,β-unsaturated moiety), a probe derived from 1 was designed and synthesized for TCI-oriented activity-based proteome profiling. By MS/MS and computer-guided molecular biology approaches, an affinity-driven Michael addition of the noncatalytic C247 residue of GAPDH was found to control the "ON/OFF" switch of apoptosis through non-canonically nuclear GAPDH translocation, which bypasses the common apoptosis-resistant route of MDR cancers.

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Prescription switching: Rationales and risks

Cited by 6 publications

References 76 publications

Cardiovascular risk profiles of GnRH agonists and antagonists: real-world analysis from UK general practice

Cardiovascular risk profiles of GnRH agonists and antagonists: real-world analysis from UK general practice

Targeting the Mevalonate Pathway in Cancer

Affinity‐Driven Covalent Modulator of the Glyceraldehyde‐3‐Phosphate Dehydrogenase (GAPDH) Cascade

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