16 minute read
COVID-19 Medications
Authors: Emilie Collongette, Pharm.D. candidate Carol Motycka, Pharm.D. Eric F. Egelund, Pharm.D., Ph.D.
COVID-19 Emergence
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COVID-19 (SARS-CoV-2) is a new strain of corona virus and was first identified in Wuhan, China in 2019. Originally coined in 1968, the coronavirus (CoVs) name originates from their “corona” or crown-like morphology observed under an electron microscope. Coronaviruses are enveloped viruses with positive-stranded RNA. 1 Coronaviruses can be subcategorized into four genera: alpha, beta, delta and gamma. Alpha- and beta-CoVs are the two that are known to infect humans. Previously, the 2002 severe acute respiratory syndrome, or SARS, outbreak was associated with beta-HCoV and then in 2012 another pathogenic beta-CoV species was responsible for the Middle East respiratory syndrome (MERS). 2
On Dec. 31, Chinese authorities reported several pneumonia cases in Wuhan, China. Most cases were associated with patients who had reported exposure to a large seafood market, suggesting another pathogenic zoonotic CoV, similar to the origins of SARS and MERS. In addition, human-to-human transmission was confirmed by the infection of health care professionals in Wuhan and outside of the Hubei district. 2,3 Human-to-human transmission is thought to occur via respiratory droplets among close contacts. The Centers for Disease Control and Prevention defines close contact for risking transmission as being within six feet of an individual with COVID-19 for a prolonged period of time or having direct contact with infectious secretions (sputum, serum, blood and respiratory droplets) from an individual with COVID-19. 3
COVID-19 Pandemic
The World Health Organization characterized COVID-19 as a pandemic on March 11. 3 At the time, more than 118,000 cases in 144 countries, and 4,291 deaths had been confirmed. The classification of COVID-19 as a pandemic is due to the “alarming levels of spread and severity.” 4 The WHO urged all countries to search for a balance between protecting health, minimizing economic and social disruptions, and respecting human rights. Four key areas of strategy were provided: 1) Preparation and readiness. 2) Detection, protection and treatment. 3) Reduction of transmission. 4) Innovation and learning. 4
COVID-19 Florida
As of April 21, the Florida Department of Health confirmed more than 25,000 total positive cases of COVID-19 in the state with a majority of counties affected. Miami-Dade, Broward, West Palm Beach, Hillsborough and Orange counties had the overall highest rates of infection. 5
COVID-19 Essential Personnel
The CDC has drafted an Interim Infection Prevention and Control Recommendations with the intention of assisting in the assessment of risk monitoring and work restrictions for health care providers with potential exposure to COVID-19. High-risk exposures are considered for health care providers who have prolonged contact with COVID-19 patients NOT wearing a facemask while the HCP’s nose and mouth were
exposed to material potentially infectious with the virus. Medium-risk exposure includes any HCP who had prolonged close contact with COVID-19 patients while they were wearing a face mask. Low-risk included brief interactions with patients with COVID-19 or prolonged close contact with patients who are wearing a facemask while the HCP also wears a facemask. 6
COVID-19 Clinical Presentation
The estimated incubation period of COVID-19 ranges from two to 14 days following exposure, with most cases occurring within four to five days of exposure. 7-9 A review of publicly reported cases in China revealed that 97.5 percent of the cases experienced symptoms within 11.5 days. The most common clinical features/symptoms include fever (88-97 percent), dry cough (57-76 percent), fatigue and myalgia (44 percent), anorexia, and dyspnea (22-45 percent). Less common symptoms include GI upset, headaches, sore throat and rhinorrhea .7-9
Clinical complications associated with progression of COVID-19 are acute respiratory distress syndrome, arrythmias, acute cardiac injury and shock. 10 Based on an overview of 44,500 COVID-19 cases from the Chinese Center for Disease Control and Prevention, 81 percent were classified as mild and had no pneumonia. Critical disease with respiratory failure, shock, or multiorgan dysfunction was 5 percent and the overall fatality rate was 2.3 percent. 10
COVID-19 Home versus Hospital Management
The CDC and WHO justify that home management is appropriate for patients with mild infection who can be appropriately isolated. 10,11 The main focus of home management is isolation and prevention of remission while monitoring for clinical deterioration. Patients with mild infections should wear facemasks when in the same room, vehicle or setting as other individuals. The CDC recommends discontinuing home isolation after at least seven days from the initial presentation of symptoms and three days since symptoms have resolved. 12 The CDC reports approximately 20-30 percent of hospitalized patients with COVID-19 have pneumonia requiring intensive care for respiratory support. Ultimately, decisions to monitor a patient in the outpatient or inpatient setting should be made on a case-by-case basis and no specific treatment for COVID-19 was available at press time.
COVID- 19 Pharmacotherapy options
A standard of care has not been established for the management of COVID-19. The American Society of Health-System Pharmacists has published an assessment of evidence for COVID-19 Related Treatment which is updated frequently. 13
Chloroquine Phosphate and hydroxychloroquine are antimalarial agents which have been shown to have in vitro activity against some coronaviruses. In addition, both drugs have immunomodulatory activity that could potentially have an ant-inflammatory like response in patients with viral infections. Clinical experience has shown possible benefit in decreasing viral load and duration of illness in COVID-19, but data is limited, and more data is needed to support safety and
efficacy. ASHP suggests chloroquine phosphate and hydroxychloroquine as potential options for COVID- 19 treatment:
DOSING:
■ Chloroquine phosphate: 500 mg PO BID X 10 days 15 ■ Chloroquine phosphate: 500 mg PO BID X 7 days (18-65 years old weighing > 50 kg) 11 ■ 500 mg PO BID days 1 &2, then 500 mg days 3-7 (wt. < 50 kg )11 ■ Chloroquine phosphate: Initial dose (600 mg PO X 1 dose), followed by 300 mg PO 12 hours following first dose, then 300 mg PO BID days 2-5 15 ■ Hydroxychloroquine: 400 mg PO BID on day 1, then 200 mg BID days 2-5 ■ Hydroxychloroquine: 100-200 mg PO BID for 5-14 days 15 ■ Hydroxychloroquine: 200 mg PO TID for 10 days 17
Hydroxychloroquine with azithromycin has shown to be effective in a preliminary studies in France in hospitalized patients with confirmed COVID-19.18 The objective was to assess the efficacy of hydroxychloroquine used alone or with azithromycin with the primary end point being a negative PCR result in nasopharyngeal sample at day six. On day six, 100 percent of patients receiving hydroxychloroquine 200 mg PO TID x 10 days WITH azithromycin 500 mg PO daily on day 1 and 250 mg PO daily days 2-5 versus 57 percent of patients receiving hydroxychloroquine 200 mg PO TID x 10 days had a negative PCR result.
The study was a small nonrandomized trial with 20 patients during which data on disease severity was unclear and information on disease progression and clinical outcomes were not reported. Therefore, additional data is needed before conclusions regarding the effects of hydroxychloroquine and azithromycin in COVID-19 patients. Hydroxychloroquine and azithromycin are associated with QT prolongation. Caution is advised for use in patients with chronic medical conditions such arrythmia, renal failure and hepatic disease. 18
Tocilizumab (Actemra ® ) is a disease modifying anti-rheumatic drug thought to potentially combat cytokine release syndrome featured in severely ill patients. 19 While a randomized, multicenter, controlled clinical trial evaluating the efficacy and safety of COVID-19 is still underway in China, the preliminary data has shown rapid fever reduction and a decreased need for supplemental oxygen after receiving tocilizumab 400 mg via IV infusion. 19-21 In China, it has been used in severely or critically ill COVID-19 patients with extensive lung lesion and high IL-6 levels. DOSING:
Tocilizumab: initial dose 4-8 mg/kg IV over more than 60 minutes. If initial dose is not effective, may administer a second dose (same dosing) after 12 hours. No more than two doses should be given; max dose 800 mg/dose. (Recommendation in China) 20
Inhaled Nitric Oxide (INOpulse ® ) is a selective pulmonary vasodilator thought to be useful in the treatment of acute respiratory distress syndrome, a common complication of COVID-19. On March 20, the FDA granted emergency expanded access allowing INOpulse ® to be immediately used for the treatment of COVID-19. 21 Inhaled nitric oxide reversed pulmonary hypertension, improved severe hypoxia, and shortened the duration of ventilator support amongst SARS-CoV patients in a small pilot study in China during the 2003 outbreak. 21 Clinical trials are evaluating the role of inhaled nitric oxide in COVID-19 treatment or prevention. DOSING:
Inhaled nitric oxide therapy was given for > three days (30 ppm on day one, followed by 20 ppm on day two and 10 ppm on days 3, then weaned on day four; therapy was resumed at 10 ppm if deteriorating oxygenation occurred (SARS-CoV patients) 22
COVID- 19 Investigational Therapeutics
Several clinical trials are ongoing for the treatment of COVID-19, some of which involve non-commercially available or FDA approved agents. Remdesivir is a broad-spectrum antiviral with activity against coronaviruses, previously tested in SARS, MERS and Ebola. Remdesivir is given via IV infusion. A Phase 3 open-label trial and a Phase 2 randomized placebocontrol trial are underway for hospitalized patients with COVID-19. 24,25 Gilead, the manufacturer, is transitioning to an expanded access program for emergency access to the drug for those severely ill patients with COVID-19. 26
Colchicine is being assessed in a phase 3 randomized double-blind trial to determine if short term treatment will reduce mortality and lung complications due to COVID-19. 27
Numerous other medications are being examined as well: statins, high dose vitamin C, zinc, among many others. For further information, The American Society of Health System Pharmacists is maintaining a table listing the various agents used in treatment as well as an assessment of those agents’ efficacy in treating COIVD-19.
COVID-19 Therapeutic Agents to Avoid
The WHO and CDC recommend to not use corticosteroids routinely in patients with COVID-19 who have developed pneumonia or acute respiratory distress syndrome unless otherwise indicated. There is no evidence to show the survival benefit of corticosteroids in patients with SARS and MERS. Delayed viral clearance, avascular necrosis, psychosis and diabetes have been shown to be potential effects associated with the use of corticosteroids in COVID-19 patients. 28,29 However, some endocrinologists recommend “a stress dose” of glucocorticoids in patients who use them on a routine basis for inflammatory conditions (e.g., asthma, arthritis).30
COVID-19 and Fish Antibiotics
Fish medications are not FDA-approved to treat humans and, therefore, do not have the labeling information for human dosing, administration or side effects. 31 Chloroquine phosphate and hydroxychloroquine are anti-viral medications available under the care/orders of a supervising provider that have shown efficacy in the treatment of COVID-19. Chloroquine phosphate is also available over the counter as an additive used to clean fish tanks.
An Arizona couple in their 60s found the formulation used in aquariums of chloroquine phosphate on their shelf and decided to self-medicate after hearing on a media outlet that it was a treatment for COVID-19. 32 After ingesting the product, the husband could not be resuscitated when he arrived at the hospital, however, the wife was able to throw up most of the chemical.
Following the incident, Banner Health, the manufacturers of the prescription formulation of chloroquine, urged individuals that self-medicating is not appropriate and dangerous. The formulations differ between the aquarium cleaning additive and the prescription drug used to treat viruses and should not be recommended for self-treatment.
COVID-19 Prescribing Patterns
The increase demand of hydroxychloroquine and chloroquine during the pandemic has led to inappropriate prescribing. Brian Brito, president of SMP Pharmacy Solutions, shared with ProPublica that the pharmacy has experienced individuals attempting to stockpile the medications for prophylactic use. SMP Pharmacy solutions had 800 tablets on a Monday and were nearly sold out in about an hour. Brito explained a doctor called and asked for 200 tablets, after the pharmacy refused to dispense such a high quantity, the doctor asked for 42 tablets, the treatment amount for two people. 33 Experiences like these have led state boards of pharmacy to take action to help prevent inappropriate prescribing and potential shortages. State boards of pharmacy in Nevada, Ohio, Texas, West Virginia, Louisiana and Idaho have developed policies to manage the supply and dispensing of rules of hydroxychloroquine, requiring a diagnosis for an indicated disease be written on the prescription. If diagnosis indicates COVID- 19, restrictionssuch asa 14-day supply limit and no refills apply. 34 The goal is to combat hoarding and maintain anadequate supply forpatients whohave been taking the hydroxychloroquine as a maintenance medication.
Conclusion
The COVID-19 pandemic is an evolving situation, placing pharmacists at the forefront of the pandemic. Pharmacists play a critical role in supporting our fellow health-care providers and patients. As the most accessible health care providers, pharmacists can help educate the public and disseminate accurate information. Aside from filling prescriptions and managing inventories, pharmacists can also counsel individuals on proper hygiene, preventative measures and symptom management. Pharmacists may encourage and refer individual with symptoms or who may have been in contact with infected persons to self-quarantine or seek medical care.
As the medication experts, pharmacists work along-side physicians, nurses, researchers and other providers in understanding the virus and establishing treatments. The world has seen a rapid increase in confirmed COVID-19 cases as testing has become more readily available. It is essential all personnel: members of the community, health care providers, essential workers, government leaders etc play a role in the global pandemic and make strides towards healing.
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Emilie Collongette is a fourth-year student pharmacist at the University of Florida College of Pharmacy Jacksonville. As an Advanced Pharmacy Practice Experience student amidst the COVID-19 pandemic, she has experienced first-hand the role pharmacist have played. During her academia rotation, Emilie was tasked with supporting the UFCOP’s faculty and staff in transitioning to 100 percent virtual learning. In addition, Emilie has had experience providing care for patients during this time as an intern for Publix Pharmacy and APPE community student. Emilie’s focus has been to support her pharmacist and provide up-to-date information to her colleagues and patients.
