key: cord-0946600-pis57zmj authors: Ailabouni, Nagham J; Hilmer, Sarah N; Kalisch, Lisa; Braund, Rhiannon; Reeve, Emily title: COVID-19 Pandemic: Considerations for Safe Medication Use in Older Adults with Multimorbidity and Polypharmacy date: 2020-04-30 journal: J Gerontol A Biol Sci Med Sci DOI: 10.1093/gerona/glaa104 sha: c7b21fb7506df5069c56cc5759b318212e3caa64 doc_id: 946600 cord_uid: pis57zmj nan A c c e p t e d M a n u s c r i p t Current clinical management of COVID-19 infection focuses on early recognition, isolation, infection control measures and provision of supportive care 7, 8 . Researchers have identified actions to help recognize COVID-19 symptoms early in older adults and provide appropriate management of the disease 9, 10 . While there is no specific antiviral treatment for COVID-19, the World Health Organization (WHO) has prioritized some medications to be further investigated in clinical trials based on in-vitro clinical effectiveness and available safety data 11 . These include oseltamavir/remdesivir, lopinavir/ritonavir, chloroquine phosphate/(hydroxy)chloroquine sulfate. 10, 11 The Clinicaltrials.gov registry has over 200 registered studies investigating COVID-19 and the Chinese Clinical Trial registry has over 500 12, 13 . Table 1 lists dosing and safety considerations in older adults for the above medications 14 . Of note, chloroquine and hydroxychloroquine have received attention for potential prevention and/or treatment of COVID-19. Both these medications are 4-aminoquinoline derivatives that differ only by a hydroxy group 14 . They have similar pharmacokinetic (PK) profiles (Table 1 ) and are immunomodulant drugs that are used to prevent and treat malaria, and in the treatment of rheumatoid arthritis and lupus 15 . In-vitro, chloroquine and hydroxychloroquine have been shown to reduce viral replication of SARS-CoV-2. 15 This has sparked interest to investigate their efficacy and clinical safety in-vivo. A c c e p t e d M a n u s c r i p t A c c e p t e d M a n u s c r i p t A number of controversial links have been made between certain medications and the risk of infection with and severity from COVID-19 infection. 21 These are particularly relevant to older people, who have a high prevalence of medication use for management of chronic diseases 5 . These associations are currently being investigated in pharmacovigilance studies and interventional clinical trials. Chronic administration of ACE inhibitors and ARBs can lead to the increased expression of Angiotensin converting enzyme 2 (ACE2) 21 , an enzyme that mediates the entry of SARS-CoV-2 into cells 22 . The clinical relevance of these claims is currently unclear and subject to confounding 23 . International cardiology societies currently recommend to continue using these medications 24,25 . The use of ibuprofen and other NSAIDs, has been raised as a concern in people with COVID-19 26 . Similar to ACE inhibitors and ARBs, long-term exposure to NSAIDs has been reported to increase ACE2 expression 21, 23 . Albeit controversial, long-term use of NSAIDs has also been associated with an increased risk of cardiovascular (CV) outcomes (e.g. stroke, myocardial infarction) 27 . Considering the higher risk of CV events during any acute respiratory tract infection, using NSAIDs (even short-term) is thought to increase this risk in A c c e p t e d M a n u s c r i p t people with COVID-19 26 . Additionally, there is a concern that fever and/or dehydration due to COVID-19 in combination with NSAID use could lead to nephrotoxicity 28 . Prescribing NSAIDs in older adults for any indication has been identified as potentially inappropriate due to the risk of several ADRs 6 . The World Health Organization (WHO) does not endorse claims that the use of NSAIDs worsens outcomes in COVID-19 7 . Current guidance recommends acetaminophen as first line treatment for fever in COVID-19 29 . When considering the use of NSAIDs in older adults, risks and benefits should be individually assessed and carefully balanced 23 . Judicious use of corticosteroids such as one or two doses, to reduce immunopathological damage in the acute phase of an infection, has been proposed for COVID-19 treatment 30 . This is currently being evaluated in clinical trials. However, prolonged administration beyond the early stage of the disease has been shown to enhance viral replication (i.e. viral rebound) and increase the risk of adverse events (e.g. acute respiratory distress syndrome) 30 . Therefore, current recommendations suggest avoiding corticosteroids when treating COVID-19 outside a clinical trial setting, unless indicated for other reasons such as septic shock or exacerbation of pre-existing chronic obstructive pulmonary disease 7, 24 . A c c e p t e d M a n u s c r i p t With the increased complexity of medication regimens and increased strains on the healthcare system due to COVID-19, medication errors and medication-related problems are more likely and can lead to significant negative health consequences. Increased vigilance to prevent errors is needed. Geriatric syndromes, including falls and delirium may be precipitated by pre-existing medications and/or by COVID-19 and could be more difficult to manage considering required COVID- A c c e p t e d M a n u s c r i p t Here we described three main considerations for medication management in older adults during COVID-19; pharmacokinetics and drug interactions when considering investigational therapies, medication reviews to simplify existing regimens and minimize iatrogenic geriatric syndromes and responding to supply shortages. Cumulatively, these considerations can help prevent avoidable drug-related adverse events and facilitate the recovery of older adults affected by A c c e p t e d M a n u s c r i p t M a n u s c r i p t A c c e p t e d M a n u s c r i p t Mainly renal excretion of metabolites MOA: Mechanism of action; PK: pharmacokinetic; CrCl: Creatinine Clearance; ESRD: End-stage Renal Disease, ACE2: Angiotensin Converting Enzyme 2; GFR: Glomerular Filtration Rate. A c c e p t e d M a n u s c r i p t M a n u s c r i p t Figure 1 Coronavirus disease (COVID-19) Pandemic Centers for Disease Control and Prevention. Severe Outcomes Among Patients with Coronavirus Disease 2019 (COVID-19) -United States European Centre for Disease Prevention and Control. Coronavirus disease 2019 (COVID-19) pandemic: increased transmission in the EU/EEA and the UK -seventh update COVID-19 Surveillance Group. Characteristics of COVID-19 patients dying in Italy. Report based on available data on Aging with multimorbidity: a systematic review of the literature Updated AGS Beers Criteria(R) for Potentially Inappropriate Medication Use in Older Adults Clinical management of severe acute respiratory infection when novel coronavirus (nCoV) infection is suspected (ncov)-infection-is-suspected COVID-19-New Insights on a Rapidly Changing Epidemic Coronavirus Disease 2019 in Geriatrics and Long-term Care: The ABCDs of COVID-19 Novel Coronavirus (COVID-19) Epidemic: What Are the Risks for Older Patients? World Health Organization (WHO). Coronavirus disease (COVID-2019) R&D IBM Micromedex® Coronavirus Disease 2019 (COVID-19) Investigational Therapies A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19 Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label non-randomized clinical trial Efficacy of hydroxychloroquine in patients with COVID-19: results of a randomized clinical trial medRxiv Clinical pharmacology in the geriatric patient Pharmacokinetic and pharmacodynamic alterations in older people with dementia Liver injury in COVID-19: management and challenges The Lancet Gastroenterology & Hepatology 2020 Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection?