AIM: To explore the level of agreement on drug-drug interaction (DDI) information listed in three major online drug information resources (DIRs) in terms of: (1) interacting drug pairs; (2) severity rating; (3) evidence rating and (4) clinical management recommendations. METHODS: We extracted DDI information from the British National Formulary (BNF), Thesaurus, and Micromedex. Following drug name normalisation, we estimated the overlap of the DIRs. We annotated clinical management recommendations either manually, where possible, or through application of a machine learning algorithm. RESULTS: The DIRs contained 51,481 (BNF), 38,037 (Thesaurus), and 65,446 (Micromedex) drug pairs involved in DDIs. The number of common DDIs across the three DIRs was 6,970 (13.54% of BNF, 18.32% of Thesaurus, and 10.65% of Micromedex). Micromedex and Thesaurus overall showed higher levels of similarity in their severity ratings, while the BNF agreed more with Micromedex on the critical severity ratings and with Thesaurus on the least significant ones. Evidence rating agreement between BNF and Micromedex was generally poor. Variation in clinical management recommendations was also identified, with some categories (i.e. Monitor and Adjust dose) showing higher levels of agreement compared to others (i.e. Use with caution, Wash-out, Modify administration). CONCLUSIONS: There is considerable variation in the DDIs included in the examined DIRs, together with variability in categorisation of severity and clinical advice given. DDIs labelled as critical are more likely to appear in multiple DIRs. Such variability in information could have deleterious consequences for patient safety, and there is a need for harmonisation and standardisation.
Aims: To continually evaluate the role of cardiovascular drugs in COVID-19 clinical outcomes. Methods: Eligible publications were identified from >500 databases on 1-Nov-2020. One reviewer extracted data with 20% of the records independently extracted/evaluated by a second reviewer. Results: Of 52,735 screened records, 429 and 390 studies were included in the qualitative and quantitative syntheses, respectively. The most-reported drugs were angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) with ACEI/ARB exposure having borderline association with positive COVID-19 status (OR 1.14, 95% CI 1.00–1.31). Among COVID-19 patients, unadjusted estimates showed that ACEI/ARB exposure was associated with hospitalization (OR 1.76, 1.34–2.32), disease severity (OR 1.41, 1.27–1.56) and all-cause mortality (OR 1.22, 1.12–1.33) but not hospitalization length (mean difference -0.27, -1.36; 0.82 days). After adjustment, ACEI/ARB exposure was not associated with positive COVID-19 status (OR 0.92, 0.71–1.19), hospitalization (OR 0.93, 0.70–1.24), disease severity (OR 1.05, 0.81–1.38), or all-cause mortality (OR 0.85, 0.71–1.01). Similarly, subgroup analyses involving only hypertensive patients revealed that ACEI/ARB exposure was not associated with positive COVID-19 status (OR 0.93, 0.79–1.09), hospitalization (OR 0.84, 0.58–1.22), hospitalization length (mean difference -0.14, -1.65; 1.36 days), disease severity (OR 0.92, 0.76–1.11) while it decreased the odds of dying (OR 0.76, 0.65–0.88). A similar trend was observed for other cardiovascular drugs. However, the validity of these findings is limited by a high level of heterogeneity and serious risk of bias. Conclusion: Cardiovascular drugs are not associated with poor COVID-19 outcomes in adjusted analyses. Patients should continue taking these drugs as prescribed.
Warfarin has existed for more than seven decades and has been the anticoagulant of choice for many thromboembolic disorders. The recent introduction of direct acting oral anticoagulants (DOACs) has however caused a shift in preference by healthcare professionals all over the world. DOACs have been found to be at least as effective as warfarin in prevention of stroke in patients with atrial fibrillation and in treatment of venous thromboembolism. In sub-Saharan Africa, however, the widespread use of DOACs has been hampered mainly by their higher acquisition costs. As the drugs come off patent, their use in sub-Saharan Africa is likely to increase. However, very few trials have been conducted in African settings, and safety concerns will need to be addressed with further study before widespread adoption into clinical practice.
Patients in sub-Saharan Africa generally have poor anticoagulation control. We review the potential reasons for this poor control, as well as the potential solutions. Challenges include the affordability and centralisation of anticoagulation care, problems with access to medicines and INR monitoring, the lack of locally-validated standardized dosing protocols, and low levels of anticoagulation knowledge among health care workers and patients. Increasing numbers of patients will need anticoagulation in the future because of the epidemiological transition in the region. We propose that locally-developed “warfarin care bundles” which address multiple anticoagulation challenges in combination may be the most appropriate solution in this setting currently.
Intense effort is underway to evaluate potential therapeutic agents for the treatment of COVID-19. In order to respond quickly to the crisis, the repurposing of existing drugs is the primary pharmacological strategy. Despite the urgent clinical need for these therapies, it is imperative to consider potential safety issues. This is important due to the harm-benefit ratios that may be encountered when treating COVID-19, which can depend on the stage of the disease, when therapy is administered and underlying clinical factors in individual patients. Treatments are currently being trialled for a range of scenarios from prophylaxis (where benefit must greatly exceed risk) to severe life-threatening disease (where a degree of potential risk may be tolerated if it is exceeded by the potential benefit). In this perspective, we have reviewed some of the most widely-researched repurposed agents in order to identify potential safety considerations using existing information in the context of COVID-19.