Ivermectin exposures reported to the Poisons Information Helpline in South Africa during the COVID-19 pandemic.

BACKGROUND: Ivermectin is an antiparasitic drug that has shown in vitro activity against COVID­19. Clinical studies supporting ivermectin for COVID­19 prevention and treatment are conflicting, with important limitations. Public support for ivermectin is significant, with extensive off-label use despite the conflicting views on its efficacy. Ivermectin tablets and injectable formulations are not registered in South Africa for human use by the South African Health Products Regulatory Authority. The National Department of Health does not currently recommend the use of ivermectin for COVID­19. OBJECTIVES: To describe cases of ivermectin exposure reported to the Poisons Information Helpline of the Western Cape (PIHWC) before and after publication of the drug's in vitro activity against SARS-CoV-2. METHODS: In a retrospective review, ivermectin-related calls reported to the PIHWC from 1 June 2015 to 30 June 2020 (period 1) were compared with calls received from 1 July 2020 to 31 July 2021 (period 2), dichotomised according to the first publication indicating ivermectin activity against SARS-CoV-2. RESULTS: Seventy-one cases were screened, and 65 were included for analysis; 19 cases were reported during period 1 and 46 during period 2. During period 2, 25 ivermectin cases (54.3%) were related to COVID­19 use. Of these, 24 cases (52.2%) involved veterinary preparations, 3 (6.5%) human preparations and 19 (41.3%) unknown preparations. Fourteen cases (73.7%) during period 1 and 30 (65.2%) during period 2 were reported to be symptomatic. The most common organ systems involved were the central nervous (n=26 cases; 40.0%), gastrointestinal (n=18; 27.7%), ocular (n=9; 13.8%) and dermatological (n=5; 7.7%) systems. CONCLUSION: Ivermectin-related exposure calls increased during study period 2, probably as a result of ivermectin being used as preventive and definitive therapy for COVID­19 in the absence of robust evidence on efficacy, dosing recommendations or appropriate formulations.

Bleeding and thrombosis outcomes in hospitalised COVID-19 patients on low-molecular-weight heparin and antiplatelet therapy.

BACKGROUND: An increased incidence of thromboembolic events in hospitalised COVID­19 patients has been demonstrated despite the use of low-molecular-weight heparin (LMWH). Antiplatelet therapy prior to admission and early in the disease course has been hypothesised to be protective against thrombosis. OBJECTIVES: To describe the bleeding and thrombosis outcomes in hospitalised patients with confirmed COVID­19 receiving LMWH, with and without concomitant antiplatelet therapy. Secondary objectives were to explore predictors of bleeding and thrombosis outcomes, and dosing practices of antiplatelet therapy and LMWH. METHODS: We conducted a descriptive, cross-sectional study of bleeding and thrombosis outcomes at Tygerberg Academic Hospital, Cape Town, South Africa, during the first COVID­19 wave, in 808 hospitalised patients with confirmed COVID­19 receiving LMWH with and without concomitant antiplatelet therapy. Multivariate logistic regression analysis was performed if predictors were deemed statistically and clinically significant. RESULTS: Patients receiving both LMWH and antiplatelet therapy had similar bleeding outcomes compared with patients only receiving LMWH (odds ratio (OR) 1.5; 95% confidence interval (CI) 0.6 - 4.0). Patients receiving both LMWH and antiplatelet therapy had increased odds of developing thrombosis compared with patients only receiving LMWH (OR 4.8; 95% CI 2.1 - 10.7). CONCLUSION: The bleeding risk in COVID­19 patients receiving both LMWH and antiplatelet therapy was not significantly increased. A potentially higher risk of thrombosis in patients receiving LMWH and antiplatelet therapy was observed. However, this could reflect confounding by indication. Randomised studies are required to further evaluate the use of antiplatelet therapy to treat hospitalised patients with COVID­19.

Bleeding and thrombosis outcomes in hospitalised COVID-19 patients on low-molecular-weight heparin and antiplatelet therapy

Background. An increased incidence of thromboembolic events in hospitalised COVID­19 patients has been demonstrated despite the use of low-molecular-weight heparin (LMWH). Antiplatelet therapy prior to admission and early in the disease course has been hypothesised to be protective against thrombosis.Objectives. To describe the bleeding and thrombosis outcomes in hospitalised patients with confirmed COVID­19 receiving LMWH, with and without concomitant antiplatelet therapy. Secondary objectives were to explore predictors of bleeding and thrombosis outcomes, and dosing practices of antiplatelet therapy and LMWH.Methods. We conducted a descriptive, cross-sectional study of bleeding and thrombosis outcomes at Tygerberg Academic Hospital, Cape Town, South Africa, during the first COVID­19 wave, in 808 hospitalised patients with confirmed COVID­19 receiving LMWH with and without concomitant antiplatelet therapy. Multivariate logistic regression analysis was performed if predictors were deemed statistically and clinically significant.Results. Patients receiving both LMWH and antiplatelet therapy had similar bleeding outcomes compared with patients only receiving LMWH (odds ratio (OR) 1.5; 95% confidence interval (CI) 0.6 - 4.0). Patients receiving both LMWH and antiplatelet therapy had increased odds of developing thrombosis compared with patients only receiving LMWH (OR 4.8; 95% CI 2.1 - 10.7).Conclusion. The bleeding risk in COVID­19 patients receiving both LMWH and antiplatelet therapy was not significantly increased. A potentially higher risk of thrombosis in patients receiving LMWH and antiplatelet therapy was observed. However, this could reflect confounding by indication. Randomised studies are required to further evaluate the use of antiplatelet therapy to treat hospitalised patients with COVID­19.

Boomslang (Dispholidus typus) envenomation in a patient on warfarin therapy.

The venom of the boomslang (Dispholidus typus) has potent effects on the coagulation system. It is known to produce a venom-induced consumptive coagulopathy (VICC) through the proposed activation of clotting factor II (prothrombin), factor X, and possibly factor IX. Warfarin, an anticoagulant medication, decreases the circulating vitamin K-dependent clotting factors II, VII, IX and X. We report a unique case of a boomslang bite in a patient on warfarin therapy. During the patient's hospital stay he developed abnormal clotting profiles indicating an underlying VICC, but without major bleeding. He received monovalent antivenom and recovered with no complications. We discuss two possible outcomes of a boomslang bite in a patient on warfarin therapy, exploring the underlying pathophysiology that could lead to the presentation of a reduced risk of overall bleeding or, alternatively, that the bleeding could be compounded and exacerbated. It is possible that in our case the anticoagulant effect of warfarin was wholly obscured by the VICC of the boomslang venom. The composition of the snake venom may have been a contributory factor in the reduced clinical bleeding observed.

Vasopressor therapy in atypical antipsychotic overdose.

Hypotension is a common presentation following an overdose of quetiapine. Adrenaline is often used as the vasopressor of choice for hypotension not responding to intravenous fluids. We present a case of quetiapine overdose with hypotension unresponsive to high-dose adrenaline. The patient was commenced on noradrenaline and made a full recovery. We highlight learning points about vasopressor therapy for atypical antipsychotic overdose. Quetiapine-induced hypotension is thought to be mediated by α1-receptor antagonism. Adrenaline is unlikely to improve blood pressure, as it is an agonist at both α- and ß-receptors. Alpha-2- and ß2-agonism can reduce sympathetic outflow and cause vasodilation, respectively, further exacerbating the hypotension. Noradrenaline is the preferred vasopressor of choice for hypotension caused by quetiapine overdose, as it has less affinity for α2- and ß2-receptors, but maintains α1-receptor agonism. Drugs with a similar mechanism of inducing hypotension should also be treated with noradrenaline as the vasopressor of choice.

Medical cannabis: What practitioners need to know.

The South African (SA) Constitutional Court recently decriminalised the private cultivation, possession and use of cannabis by adults. Cannabis contains varying amounts of the cannabinoids delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), depending on various cultivation factors. No commercial plant-derived cannabis products are currently registered by the SA Health Products Regulatory Authority (SAHPRA) for medical use. Such products are therefore unregulated, but are freely available in SA, and may be of inadequate quality and unverified composition, and not guaranteed to be safe or effective. SAHPRA has to date approved only one synthetic medical cannabis product, dronabinol. Evidence supporting benefit from medical cannabis exists for two drug-resistant childhood forms of epilepsy, Dravet syndrome and Lennox-Gastaut syndrome. Adjuvant therapy with medical cannabis can reduce seizure frequency for Lennox-Gastaut syndrome and Dravet syndrome by 18.8% and 22.8%, respectively, and may be beneficial for other rare forms of epilepsy. There is moderate evidence for chemotherapy-induced nausea and vomiting with the synthetic cannabinoids. Multiple sclerosis-associated spasticity showed a small clinical improvement in self-reported spasticity when a purified form of THC/CBD was added to existing therapy. Currently, low-level or no convincing evidence exists for the use of medical cannabis for chronic pain, sleep and weight disorders, and neuropsychiatric disorders. Cannabis is associated with a greater risk of adverse effects than active and placebo controls, and may be involved in clinically significant drug-drug interactions. The evolving regulatory and legal landscape on the use of medical cannabis will guide prescription and recreational use in the coming years.

Current evidence for directed and supportive investigational therapies against COVID-19.

Coronavirus disease 2019 (COVID-19) is a global health crisis. There is currently a great need for effective and safe therapies directed at the disease, but no drugs are presently registered for use in COVID-19. Several directed therapies have been proposed, and most are still in clinical trials. Currently available published, peer-reviewed results mostly involve small sample sizes with study limitations restricting the interpretation of the findings. Many trials currently published also do not have a control group, limiting the interpretation of the effect of the intervention. Investigational directed therapies as well as investigational supportive therapies against COVID-19 are reviewed here. Chloroquine and hydroxychloroquine show promise as directed therapies, but current trial results are conflicting. Lopinavir/ritonavir also shows potential, but was started late in the disease course in most trials. No randomised controlled evidence is currently available for remdesivir and favipiravir. Corticosteroid use is not recommended for directed therapy against COVID-19, and the role of tocilizumab is currently unclear, based on limited evidence. Early initiation of investigational directed therapies may provide benefit in selected patients. The results from larger randomised controlled trials will clarify the place of these therapies in COVID-19 treatment.