Pharmaceutical care of chloroquine phosphate in elderly patients with coronavirus pneumonia (COVID‐19)

1Department of Pharmacy, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Assessment of Clinical Drugs Risk and Individual Application Key Laboratory, Chinese Academy of Medical Sciences, Beijing, China 2Department of Pharmacy Administration and Clinical Pharmacy, School of Pharmaceutical Sciences, Peking University, Beijing, China 3Clinical Trial Center, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Assessment of Clinical Drugs Risk and Individual Application Key Laboratory, Chinese Academy of Medical Sciences, Beijing, China


| INTRODUC TI ON
Since the outbreak of the new coronavirus pneumonia  in December 2019, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it has spread to the whole country. By 12:00 am on February 28, 2020, a total of 78 632 cases had been confirmed nationwide, including 2747 deaths. At present, it has been found that people of all ages are generally susceptible to the new virus, but the elderly and patients with multiple chronic diseases have the highest rates of severe illness and mortality. 1 to apply to adults aged 18-65 years: patients with a bodyweight of 50 kg or above, 500 mg, bid, for 7 days; and those with a bodyweight of 50 kg or less, 500 mg, bid, on the 1st and 2nd days, and 500 mg, qd, on the 3rd to 7th days, with a course of treatment of 7 days.
Chloroquine phosphate is an antimalarial drug that has been on the market for many years. In 1820, the famous French pharmacists Pelletier and Caventou successfully extracted the earliest pure antimalarial drug, quinine (also known as cinchona), from cinchona bark.
German scientist Andersag was the first to synthesize chloroquine in 1934, which caused serious adverse drug reactions ("cinchona reaction") to some users due to excessive dosage of chloroquine. In 1944, scientists modified the structure of chloroquine by adding a hydroxyl group to it, and developed a new antimalarial drug, hydroxychloroquine, which was less toxic and more effective against malaria. 5 At present, two independent experiment teams from China have confirmed that chloroquine has an impact against the SARS virus in vitro. 6 This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
At present, the safety of chloroquine phosphate in the treatment of elderly patients with COVID-19 cannot be determined, but the rate of critical illness in the elderly is high and chloroquine phosphate can still be used as an alternative antiviral drug for the elderly. The use of chloroquine phosphate is prohibited in the following elderly patients: those who are clearly allergic to 4-aminoquinoline compounds; those with arrhythmia (eg, conduction block) or chronic heart disease; those with chronic liver and kidney diseases who are reaching the terminal stage; those with known retinal disease or hearing loss; those with known psychiatric disorders; those with skin diseases (including rashes, dermatitis, and psoriasis); and those with glucose-6-phosphate dehydrogenase deficiency.

| CHLORO QU INE PHOS PHATE FOR TRE ATMENT OF ELDERLY WITH COVID -19
Based on the published clinical guidelines and research results, this paper proposes the following pharmaceutical care for the elderly using chloroquine phosphate in the treatment of COVID-19.

| Administration method of chloroquine phosphate
Oral administration of chloroquine phosphate is the only suggested administration in elderly patients.

| Dosage of chloroquine phosphate
For elderly patients with a bodyweight of more than 50 kg, chloroquine phosphate 500 mg orally, bid, for 7 days is recommended. For those with a bodyweight of 50 kg or less, 500 mg, bid, on the 1st and 2nd days, and 500 mg, qd, on the 3rd to 7th days, with a course of treatment of 7 days is recommended. According to the Wuhan Institute of Virology, Chinese Academy of Sciences, the lethal dose of chloroquine phosphate in adults is 2-4 g and doses should be closely monitored during the treatment period. The concentration of chloroquine phosphate is maintained for a long time, the plasma proteinbinding rate is about 55%, and the half-life is 2.5-10 days. The drug is metabolized by the liver, and 10%-15% of the drug is excreted by the kidney as the original. Older patients with impaired kidney function may be at greater risk for toxic reactions to the drug. Elderly patients are more likely to suffer from decreased renal function, decreased metabolism of drugs, and weakened excretory function. Therefore, the drug residual dose in patients taking chloroquine phosphate for 7 consecutive days may reach or even exceed the lethal dose. 9 Oral chloroquine can be quickly absorbed. Elderly patients should be advised to take it with food. Serious toxic reactions can occur within 1 to 3 hours, or even a few minutes after use.
Acute poisoning can be fatal, with a lethal dose as low as 50 mg/ kg. Death can occur within 2 to 3 hours. Once the above symptoms appear, the medication should be discontinued immediately and symptomatic treatment should be carried out, especially to maintain cardiopulmonary function. Refer to the treatment advice for acute hydroxychloroquine poisoning: induce vomiting or emptying of the stomach contents as soon as possible; within half an hour of taking the medicine, you can take activated carbon powder to inhibit further absorption of the drug, and use angiotensin drugs when shock occurs; provide fluid replacement at the same time; and provide plenty of ammonium chloride (8 g/day) to promote the excretion of the drugs. Acute poisoning survivors should be closely monitored for at least 6 hours, even if they show no symptoms.

| Adverse drug reactions of chloroquine phosphate
The main adverse reactions of chloroquine phosphate are as follows: If white blood cells progressively decrease or anemia and thrombocytopenia progressively increase, the dosage should be reduced or discontinued.
2. Routine electrocardiogram examination should be conducted before treatment and the electrocardiogram should be monitored at 4. Regularly check the patient's ankle and knee reflexes in case the medicine causes skeletal muscle injury. Elderly patients often spend a long time in bed, which may mask such symptoms, so the examination process should be especially careful.

Pay attention to the mental and psychological state of elderly
patients. In the isolation process of treatment, patients with neopneumonia may suffer from excessive pressure, resulting in forgetfulness, insomnia, depression, and so forth, so attention should be paid to distinguish these symptoms from the adverse reactions caused by chloroquine.

| Drug interactions of chloroquine phosphate
According to the drug instructions of chloroquine phosphate, it can interact with the following drugs, which may lead to adverse reactions and adverse events when used together.  Furthermore, staff should monitor and report adverse drug reactions in strict accordance with the requirements of the measures for the reporting, monitoring, and management of adverse drug reactions, so as to ensure drug safety for the elderly during the treatment of COVID-19.

CO N FLI C T S O F I NTE R E S T
Nothing to disclose.

AUTH O R CO NTR I B UTI O N S
Xuelin Sun and Xin Hu conceptualized the study. Xuelin Sun wrote the original draft of the manuscript. Shaoqiang Li provided methodology. Xin Hu provided data resources and supervised the study.
Kexin Li reviewed and edited the manuscript.