Vaccines have reduced the transmission and severity of COVID‐19, but there remains a paucity of efficacious treatment for drug‐resistant strains and more susceptible individuals, particularly those who mount a suboptimal vaccine response, either due to underlying health conditions or concomitant therapies. Repurposing existing drugs is a timely, safe and scientifically robust method for treating pandemics, such as COVID‐19. Here, we review the pharmacology and scientific rationale for repurposing niclosamide, an anti‐helminth already in human use as a treatment for COVID‐19. In addition, its potent antiviral activity, niclosamide has shown pleiotropic anti‐inflammatory, antibacterial, bronchodilatory and anticancer effects in numerous preclinical and early clinical studies. The advantages and rationale for nebulized and intranasal formulations of niclosamide, which target the site of the primary infection in COVID‐19, are reviewed. Finally, we give an overview of ongoing clinical trials investigating niclosamide as a promising candidate against SARS‐CoV‐2.
Objectives: To determine if a specific intervention reduces the composite of progression of patients with COVID-19-related disease to organ failure or death as measured by time to incidence of any one of the following: death, invasive mechanical ventilation, ECMO, cardiovascular organ support (inotropes or balloon pump), or renal failure (estimated Cockcroft Gault creatinine clearance <15ml/min). Trial design: Randomised, parallel arm, open-label, adaptive platform Phase 2/3 trial of potential disease modifying therapies in patients with late stage 1/stage 2 COVID-19-related disease, with a diagnosis based either on a positive assay or high suspicion of COVID-19 infection by clinical, laboratory and radiological assessment. Participants: Patients aged 18 and over, with a clinical picture strongly suggestive of COVID-19-related disease (with/without a positive COVID-19 test) AND a risk count (as defined below) >3 OR ≥3 if risk count includes "Radiographic severity score >3". A risk count is calculated by the following features on admission (1 point for each): radiographic severity score >3, male gender, non-white ethnicity, diabetes, hypertension, neutrophils >8.0 x10 9 /L, age >40 years and CRP >40 mg/L. Patients should be considered an appropriate subject for intervention with immunomodulatory or other disease modifying agents in the opinion of the investigator and are able to swallow capsules or tablets. The complete inclusion and exclusion criteria as detailed in the Additional file 1 should be fulfilled. Drug specific inclusion and
Vaccines have reduced the transmission and severity of COVID-19 but there remains a paucity of efficacious treatment for drug resistant strains and more susceptible individuals. Repurposing existing drugs is a timely, safe and scientifically robust method for treating pandemics such as COVID-19. Here, we review the pharmacology and scientific rationale for repurposing niclosamide, an anti-helminth already in human use as a treatment for COVID-19. In addition to potent antiviral activity, niclosamide has shown pleiotropic anti-inflammatory, antibacterial, bronchodilatory and anticancer effects in numerous pre-clinical and early clinical studies. The advantages and rationale for nebulised and intranasal formulations of niclosamide, which target the site of primary infection in COVID-19, are reviewed. Finally, we discuss the TACTIC-E clinical trial, an international COVID-19 therapeutic platform trial for the use of licensed and novel therapeutic agents, which is investigating niclosamide as a promising candidate against SARS-CoV-2.
Little is known about morbidity due to drug-related hyponatraemia, despite hyponatraemia being a common side effect of frequently prescribed medicines. We conducted a 12-month retrospective service evaluation of hospital admissions due to drug-related hyponatraemia to determine what drugs are contributing factors, describe patient demographics and burden of morbidity. This was undertaken at a large acute UK hospital and drug-related hyponatraemia was defined by admissions where hyponatraemia was coded as the principal diagnosis and specific medication(s) were recorded as either contributory factor(s) or the principal cause of hyponatraemia and these medication(s) were discontinued. Of 131 hyponatraemia admissions, 71 (54%) were drug-related. Angiotensin converting enzyme inhibitors/ angiotensin receptor blockers, proton pump inhibitors and thiazide diuretics were drug classes most commonly associated. 61% of patients were women, median age 81 (IQR15.5) years, 61% were on more than 2 implicated drugs. The median length of stay was 4 (2-9 days IQR). This study highlights that elderly woman on more than 2 drugs that can cause hyponatraemia, constituted the majority of patients admitted to hospital with drug-related hyponatraemia.
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