COVID-19 and Pharmacotherapy

The first chart below provides information or resources on pharmacotherapy of interest for COVID-19, the disease caused by the SARS-CoV-2 virus. Additional resources on pharmacotherapy, which are frequently updated, include:

At this point, no pharmacotherapy has been proven effective for COVID-19, so treatment is largely supportive. Resources pertinent to supportive therapy include:

The second chart below addresses common questions about pharmacotherapy as it relates to COVID-19.

**Search www.clinicaltrials.gov for the latest information on COVID-19 clinical trials.**

Abbreviations: ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker; ARDS = acute respiratory distress syndrome; COPD = chronic obstructive pulmonary disease; CT = computed tomography; EUA = Emergency Use Authorization; IDSA = Infectious Diseases Society of America; IL = interleukin; NSAIDs = nonsteroidal anti-inflammatory drugs; SARS = severe acute respiratory syndrome; SARS-CoV-2 = the virus that causes COVID-19 disease; tPA = tissue plasminogen activator; TNF = tumor necrosis factor

TREATMENTS OF INTEREST

Drug

Pertinent Information or Resources
Note that DOSES provided are examples only for ADULTS; the optimal dose has not been determined for any treatment.

Anakinra (Kineret)

Anakinra is an IL-1 antagonist. IL-1 may have a role in ARDS.65

Anakinra 5 mg/kg twice daily intravenously in moderate to severe ARDS (non-ventilator) and inflammation (elevated C-reactive protein and/or ferritin) (n=29) was associated with improved survival compared to a similar historical cohort (90% vs 56%, p = 0.009).65 These patients also received hydroxychloroquine and lopinavir/ritonavir.65 A lower dose of anakinra (100 mg twice daily subcutaneously) did not seem to provide benefit.65

Azithromycin

Macrolides have in vitro antiviral (e.g., Zika, Ebola), anti-inflammatory, and immunomodulatory activity.2,7

Insufficient evidence to support widespread use [Evidence level C].2,28

Was used in a small, widely publicized study with hydroxychloroquine in six patients to prevent bacterial superinfection in COVID-19 patients (See hydroxychloroquine, below).2 Subsequent observational data including 74 additional patients suggests that the combination can reduce viral load and perhaps improve the clinical course, but there was no comparator group.28

NIH guidelines recommend against the use of azithromycin plus hydroxychloroquine outside of a clinical trial.50

Studies for COVID-19 treatment include various dosing regimens (usually azithromycin 500 mg x 1 then
250 mg once daily for four days) WITH chloroquine, hydroxychloroquine, or other antimicrobials. See www.clinicaltrials.gov for the latest information on these studies.

When used with hydroxychloroquine or chloroquine (and other QT prolonging medications), QT prolongation is of increased concern.2,4,6

Aviptadil

Investigational synthetic form of vasoactive intestinal polypeptide. Has anti-IL-6 and anti-TNF activity. Phase I trial suggests benefit in ARDS. No COVID-19 data.

Clinical trial is planned for COVID-19-associated ARDS. See www.clinicaltrials.gov for more information.

Baloxavir (Xofluza)

No COVID-19 data.

Chloroquine phosphate*

*Chloroquine phosphate
500 mg = chloroquine base 300 mg6

Efficacy

  • Inhibits SARS-CoV-2 in vitro,2 but clinical trials have not shown benefit against other viruses.18 Also has immunomodulating effects.26
  • Insufficient evidence to support widespread use.3
  • For COVID-19 pneumonia, reportedly speeds clinical improvement and viral clearance.3
  • Clinical trials are planned on the use of chloroquine to prevent COVID-19 in healthcare workers.
  • See www.clinicaltrials.gov for regimens being studied.

Dosing

  • The FDA is suggesting, for patients weighing ≥50 kg, a chloroquine phosphate dose of 1 g on day one, followed by 500 mg once daily for four to seven days.4 U.S. providers can request chloroquine through their local health department (EUA) for hospitalized patients unable to participate in a clinical trial.4
  • Additional dosing regimens from International consensus documents from around the world include:
  • chloroquine phosphate 500 mg twice daily for ten days for COVID-19 pneumonia.6
    • chloroquine phosphate 500 mg twice daily for ten days for patients with mild symptoms plus comorbidities, or more severe disease. The duration can be reduced to five days or extended to 20 days, depending on clinical severity.6
    • chloroquine base 600 mg x 1, then 300 mg 12 hours later, then 300 mg twice daily on days two through five for intensive care patients or patients requiring hospital admission and oxygen.6 (The five-day duration was chosen to minimize adverse effects, giving consideration to chloroquine’s long half-life [~30 hours]).6

Safety

  • Due to the risk of arrhythmias, the FDA recommends against chloroquine use for COVID-19 outside of the hospital setting or a clinical trial.53
  • A fact sheet on chloroquine for COVID-19 is available from the FDA (https://www.fda.gov/media/136535/download).
  • Adverse effects are not well-characterized at the doses studied for COVID-19. In general, potential adverse effects include: gastrointestinal side effects (take with food or milk), headache, hypoglycemia, QT prolongation and other conduction disturbances (especially with hypokalemia, hypomagnesemia, or heart disease), cardiomyopathy, myopathy, movement disorders, neurotoxicity, ocular toxicity, ototoxicity, anemia, thrombocytopenia, neutropenia, bone marrow suppression, serious dermatologic reactions, and psoriasis flare.4,27 Monitor electrolytes, glucose, complete blood count, electrocardiogram, baseline renal and hepatic function, knee and ankle reflexes, vision, and mental status.4,6,27
  • A Brazilian study of chloroquine phosphate 600 mg twice daily vs 450 mg twice daily stopped the high-dose arm due to higher instance of QT prolongation >500 milliseconds (18.9% vs 11.1%) and mortality (39% vs 15%).41 All patients received azithromycin.41
  • When used with azithromycin (and other QT-prolonging medications), QT prolongation is of increased concern.2,6

Colchicine

Based on its anti-inflammatory effect, there is interest in using colchicine to alter the clinical course of COVID-19 in both inpatients and higher-risk outpatients.

Clinical trials are underway. See www.clinicaltrials.gov for more information.

Keep in mind colchicine’s toxicities and drug interactions. See our chart, Colchicine Dosing and Interactions, for details.

Convalescent Plasma (COVID-19)

No large studies have been published, but small case series in patients hospitalized with severe COVID-19 show promise (e.g., defervescence, radiographic improvement, improved oxygen support requirements, viral clearance, improved clinical condition).62-64 It appears well-tolerated.62-64 Concerns include allergic reaction, viral infection, and increased clotting risk.70,71

There are three pathways for administering or studying COVID-19 convalescent plasma: clinical trials (www.clinicaltrials.gov or https://covidcp.org/), expanded access (https://uscovidplasma.org), or single patient emergency IND. The FDA has guidance for use of convalescent plasma at https://www.fda.gov/vaccines-blood-biologics/investigational-new-drug-ind-or-device-exemption-ide-process-cber/recommendations-investigational-covid-19-convalescent-plasma.

See https://www.ccpp19.org/ or https://uscovidplasma.org to find out how recovered patients can donate their plasma.

Corticosteroids

The World Health Organization Guidelines recommends that at this time, outside of clinical trials, corticosteroids should be reserved for patients with specific indications for them (e.g., sepsis, COPD, asthma), with consideration to risk vs benefit.10

The CDC recommends that corticosteroids be avoided because of the potential for prolonging viral replication, increasing need for mechanical intubation, or increasing mortality, as observed in MERS-CoV patients, unless indicated for other reasons.11

The IDSA recommends corticosteroids only for patients with ARDS, in the context of a clinical trial.46

NIH guidelines relating to corticosteroid use are available at https://covid19treatmentguidelines.nih.gov/concomitant-medications/.

Corticosteroids appeared to be ineffective and possibly harmful for SARS, but are being studied for COVID-19.9,10 In one institution in China, methylprednisolone use in patients with COVID-19 ARDS was associated with reduced mortality.16 Conversely, a meta-analysis of over 5,000 patients found longer hospital stays and higher mortality.9

Dapagliflozin

No data.

Dapagliflozin is being studied in COVID-19 patients with respiratory failure and with hypertension, diabetes, heart disease, or advanced renal disease to prevent organ failure, based on its known renal and cardiac benefit (DARE-19 study).

See www.clinicaltrials.gov for more information.

Famotidine

Interest in famotidine as a COVID-19 treatment stems from observations in China that patients who were taking famotidine who were infected with COVID-19 had better outcomes.55

In a retrospective U.S. study, any famotidine use (10 to 40 mg/day) within 24 hours of admission was associated with reduced need for mechanical ventilation or death in hospitalized COVID-19 patients.67

A clinical trial using high-dose intravenous famotidine is underway. See www.clinicaltrials.gov for more information.

Hydroxychloroquine

Efficacy

  • Is a more potent inhibitor of SARS-CoV-2 than chloroquine in vitro.2 Also has immunomodulating effects.27
  • Insufficient evidence to support widespread use [Evidence level C].2,29
  • Early enthusiasm for hydroxychloroquine was based on a widely publicized open-label, randomized study in hospitalized patients testing positive for SARS-CoV-2.2 Six of 26 hydroxychloroquine patients were lost to follow-up: one due to death, three due to intensive care admission, one due to side effects (nausea), and one who left the hospital. Viral clearance at day six was 70% in the 20 remaining hydroxychloroquine patients vs 12.5% of the control patients (n = 16).2 Six treated patients also received azithromycin 500 mg on day one, then 250 mg on days two through five to prevent bacterial infection.2 In the combination group, viral clearance was 100% at day six vs 57.1% in the hydroxychloroquine-alone group.2 Also see subsequent observational data under “Azithromycin,” above.
  • In a pilot study in China, 30 patients were randomized to hydroxychloroquine 400 mg/day (it is unclear if this was divided) for five days, or usual care. There was no difference between groups in viral clearance at day seven, length of stay, or time to defervescence.29 In a study of 62 hospitalized patients with mild disease, 31 patients were randomized to hydroxychloroquine 200 mg twice daily. Time to recovery (defervescence and cough remission) was shortened by about one day in the treatment group. On day six, pneumonia was improved per CT in more patients in the treatment group. Four patients progressed to severe disease, all in the control group.39 A subsequent open-label Chinese study (n=150) randomized patients to usual care or hydroxychloroquine 1,200 mg/day for three days, then 800 mg/day for two (mild to moderate disease) or three weeks (severe disease).42 Viral clearance was similar on days 4, 7, 10, 14, 21, and 28 for the two groups. Hydroxychloroquine did not seem to hasten symptom improvement. Thirty percent of hydroxychloroquine patients had adverse effects.
  • A retrospective French cohort study found no benefit of early hydroxychloroquine administration to 84 hospitalized patients in regard to need for intensive care, or mortality.43
  • Similarly, in a retrospective U.S. Veterans Affairs study (n=368), hydroxychloroquine, alone or with azithromycin, was not associated with reduced need for mechanical ventilation in hospitalized patients. Mortality was higher in patients who received hydroxychloroquine alone vs no hydroxychloroquine.49
  • Other retrospective U.S. studies suggest no benefit. In one (n = 1,376), patients received hydroxychloroquine 600 mg twice daily on day 1, then 400 mg daily for a median of five days. Some patients also received azithromycin or sarilumab. About half of patients began treatment within 24 hours of presentation. Hydroxychloroquine use was not associated with a reduced risk of a composite outcome of death or intubation.60 In another study (n=1,438), neither hydroxychloroquine alone, azithromycin alone, nor the combination was associated with improved in-hospital mortality, but the combination was associated with cardiac arrest.66

Other Dosing Regimens

  • The FDA is suggesting, for hospitalized patients weighing ≥50 kg, a dose of 800 mg on day one, followed by 400 mg once daily for four to seven days.31 U.S. providers can request hydroxychloroquine through their local health department (EUA) for hospitalized patients unable to participate in a clinical trial.31
  • Some U.S. clinicians have reported anecdotally using 400 mg twice daily on day one, then 400 mg once daily for five days or 200 mg twice daily for four days; or 600 mg twice daily on day one, then 400 mg once daily on days two through five.32
  • An Italian guideline suggests 200 mg twice daily for ten days for patients with mild symptoms plus comorbidities, or more severe disease.6 The duration can be reduced to five days or extended to 20 days, depending on clinical severity.6
  • Clinical trials are ongoing on the use of hydroxychloroquine to prevent COVID-19 in healthcare workers.
  • See www.clinicaltrials.gov for regimens being studied, including the NIH-sponsored ORCHID study (search identifier NCT04332991)(400 mg twice daily on day one, then 200 mg twice daily for four days).

Safety

  • Fewer adverse effects and drug interactions than chloroquine.2
  • Due to the risk of arrhythmias, the FDA recommends against hydroxychloroquine use for COVID-19 outside of the hospital setting or a clinical trial.53
  • A fact sheet on hydroxychloroquine for COVID-19 is available from the FDA (https://www.fda.gov/media/136537/download).
  • Adverse effects are not well-characterized at the doses studied for COVID-19. In general, potential adverse effects include: gastrointestinal side effects (take with food or milk), headache, hypoglycemia, QT prolongation and other conduction disturbances (especially with hypokalemia, hypomagnesemia, or heart disease), cardiomyopathy, myopathy, movement disorders, neurotoxicity, ocular toxicity, ototoxicity, anemia, thrombocytopenia, neutropenia, bone marrow suppression, serious dermatologic reactions, and psoriasis flare.27,31 Monitor electrolytes, glucose, complete blood count, electrocardiogram, baseline renal and hepatic function, knee and ankle reflexes, vision, and mental status.6,27,31
  • When used with azithromycin (and other QT-prolonging medications), QT prolongation is of increased concern.2,6 Information on managing QT prolongation risk in these patients is available at https://www.ahajournals.org/doi/pdf/10.1161/CIRCULATIONAHA.120.047521.
  • A hydroxychloroquine suspension can be made by triturating 15 hydroxychloroquine sulfate 200 mg tablets to a fine power with a mortar and pestle. Levigate to a paste with a small amount of base (Oral Mix or Oral Mix SF). Add base by geometric dilution. Transfer to a graduated cylinder. Rinse mortar and pestle with base. QS with base to 120 mL. Transfer to an amber polyethylene terephthalate bottle. Shake well. Stable for 112 days at room temperature or under refrigeration.33

IL-6 antagonist

Tocilizumab (Actemra) sarilumab (Kevzara); siltuximab (Sylvant).

Anti-IL-6 monoclonal antibody.

Some, but not all, data from China suggests an association between elevated IL-6 and severe COVID-19 disease.18

Anecdotal reports and case series suggest benefit for tocilizumab (Actemra).18,68 One or two doses of 400 to 800 mg (4 to 8 mg/kg) has been used.18,68

May cause increased infections, neutropenia, thrombocytopenia, and elevated liver enzymes.1,34-38

Not for routine use. Clinical trials are planned or underway for treatment of pneumonia or cytokine storm. See www.clinicaltrials.gov for more information.

Outside of a clinical trial, limit to patients with evidence of cytokine storm (e.g., elevated ferritin, elevated IL-6, etc), with specialist consultation.44

Janus Kinase Inhibitors (Ruxolitinib [Jakafi], etc)

No data.

Interest based on potential to block IL-6 effects, reduce cytotoxic T cells, and increase regulatory T cells.

See www.clinicaltrials.gov for more information.

Lopinavir/ritonavir (Kaletra)

Lopinavir/ritonavir has not demonstrated anti-SARS-CoV-2 activity in humans.15 Small study suggested benefit (reduced composite endpoint of ARDS or death) for 2003 SARS vs historical control.17

Results from a randomized, open-label study (n=199) suggest it might reduce complications such as acute kidney injury, secondary infections, or need for mechanical ventilation in patients with COVID-19 pneumonia.15 However, time to clinical improvement was not reduced (main outcome measure).15 Gastrointestinal adverse effects may limit use.15,30

There is interest in studying lopinavir/ritonavir earlier in the disease course, or in combination with other medications.15 Use with ribavirin and interferon beta-1b early in the disease course (mean five days from symptom onset) was compared to lopinavir/ritonavir alone in hospitalized patients (n=127).58 In this open-label study, median time to viral clearance was seven days with combination therapy vs 12 days for lopinavir/ritonavir alone.58 Alleviation of symptoms occurred in four days vs eight days, respectively (p<0.0001).58

Additional clinical trials are planned or underway. See www.clinicaltrials.gov for more information.

Losartan, Telmisartan

Studies in mice suggest that ARBs can reduce lung damage caused by SARS-CoV.13

Clinical trials are underway for treatment of COVID-19. See www.clinicaltrials.gov for more information.

Oseltamivir

Not expected to be effective against SARS-CoV-2 because SARS-CoV-2 does not use neuraminidase.26

Has been used for COVID-19 pneumonia, but there is no efficacy data.12

Remdesivir

Remdesivir has in vitro activity against SARS-CoV-2.40

In a cohort of 53 evaluable patients treated with remdesivir for severe COVID-19 disease, use was associated with clinical improvement in regard to oxygen support requirements in 68% of patients.40 Mortality was 13%, which is less than in other case series and cohorts.40 The most common adverse events were liver enzyme elevation (23%), diarrhea (9%), rash, renal impairment, hypotension (8%), acute kidney injury, atrial fibrillation, multiorgan dysfunction, hypernatremia, and venous thrombosis (6%).40 Causality could not be assessed due to the effects of COVID-19 itself.40 Based on previous data, mild to moderate transaminase elevations are expected with remdesivir.40 Viral load was not evaluated,40 but in a previous case report, virologic improvement was seen.8

Preliminary analysis of a double-blind, placebo-controlled trial (n = 1,063), remdesivir seemed to shorten time to recovery (11 days vs 15 days; p <0.001), but mortality was not statistically different (8% vs 11.6%; p = 0.059).54,72 Similarly, a Chinese study found a nonsignificant trend toward faster recovery.61

U.S.: Remdesivir is being distributed to select hospitals by the government through Emergency Use Authorization.57 This is a rapidly changing situation. For other potential opportunities for availability, see www.clinicaltrials.gov, www.gilead.com/remdesivir, or contact Gilead at 833-445-3230 (GILEAD-0) or GileadClinicalTrials@gilead.com.

Canada: Remdesivir is available through an Expanded Access Treatment Protocol at approved clinical trial sites. A list of active sites is available at https://www.canada.ca/en/health-canada/services/drugs-health-products/covid19-clinical-trials/list-authorized-trials.html and at www.clinicaltrials.gov. At this point, Gilead is not accepting more sites for consideration. Compassionate use requests continue to be reviewed for pregnant women and children <18 years of age with confirmed severe COVID-19.59

Ribavirin

Not potent enough to be effective at safe doses; hematologic toxicity precludes use.26 See lopinavir/ritonavir section for information on combination use.

Statins

No data.

Interest based on cardiovascular damage noted in COVID-19 patients and anti-inflammatory effects. Simvastatin might also block viral cell entry.

NIH guidelines recommend against use specifically for COVID-19 treatment outside of a clinical trial.

See www.clinicaltrials.gov for more information on planned or ongoing studies.

tPA (alteplase)

No data.

Interest based on reports of hypercoagulability in COVID-19 patients.19

Studies underway to treat ARDS in COVID-19 patients.19

Vaccines

Due to evidence of a non-specific protective effect against respiratory infections, BCG vaccine is being studied to prevent COVID-19 disease in healthcare workers. See www.clinicaltrials.gov for more information.

Oral polio vaccine has been mentioned on the internet, but no trials are planned at this time.

Vitamin C

Intravenous vitamin C is being studied for treatment of severe COVID-19 disease based on previous data in sepsis and ARDS. However, there is no clear evidence of benefit even for these conditions.48

Oral vitamin C is being studied for treatment of COVID-19 disease in the outpatient setting, and as prophylaxis.

See www.clinicaltrials.gov for more information on these planned or ongoing studies.

Vitamin D

There is false information circulating that vitamin D is recommended by health officials. Interest in vitamin D stems from its effects on the immune system and pulmonary ACE2 expression. Studies are planned or underway using vitamin D for prevention or as a treatment adjunct. See www.clinicaltrials.gov for more information.

Zinc

Zinc has in vitro activity against SARS-CoV.47

Studies of oral zinc, alone or in combination (e.g., with vitamin C, vitamin D, hydroxychloroquine [purported to help zinc get inside the cells47], azithromycin) to prevent COVID-19 disease are planned or ongoing.

See www.clinicaltrials.gov for more information.

FAQs ABOUT COVID-19 AND PHARMACOTHERAPY

There is a lot of misinformation regarding COVID-19 on the internet. Use this table to help answer patient questions and correct misconceptions.

Clinical question

Pertinent information or resource

Do ACE inhibitors or ARBs make COVID-19 worse?

The SARS-CoV-2 virus uses ACE2 to enter cells.13 ACE inhibitors and ARBs may upregulate ACE2.13 In theory, these drugs could thereby facilitate virus entry into cells.13 But on the other hand, blocking angiotensin could reduce lung injury.13

No evidence suggests that patients taking an ACEI or ARB are more susceptible to COVID-19 infection, or that these medications worsen outcomes.14,51,52,69 One cohort study even suggests reduced mortality in COVID-19 patients taking them for other indications.51 Furthermore, we know that these drugs benefit patients with diabetic nephropathy and cardiovascular disease, populations at risk of severe COVID-19 disease.13,22

Patients should continue these medications. See statements from:

Can NSAIDs be used in COVID-19-infected patients?

Anecdotal reports regarding worse COVID-19 outcomes in patients taking NSAIDs have spread in the media and on social media, including via a tweet from a French health official.14,23 In 2019, a French report suggested that NSAIDs could worsen infections, mainly Strep, perhaps by masking symptoms.24,25 However, there is currently no reliable clinical data supporting worse outcomes in patients taking NSAIDs or aspirin.14,20 Preclinical data is mixed on the potential effects of NSAIDs on COVID-19 (increased expression of ACE2, which the virus uses to enter cells, vs potential antiviral activity of NSAIDs).14

Patients taking low-dose aspirin should not stop taking it because of COVID-19 concerns.14

Neither the FDA nor Health Canada is advising changes to NSAID use due to COVID-19.20,21

Are any supplements effective for prevention or treatment of COVID-19?

There is no scientific evidence that any alternative remedies can prevent or treat COVID-19, and some products may not be safe.5 See our Natural Medicines database (www.naturaldatabase.com) for information on efficacy and safety of specific alternative medicines.

A study using honey as an adjunct to standard care for treatment of COVID-19 is planned.

Several studies are looking at multivitamin/mineral combos as adjuncts for treatment or prevention. See www.clinicaltrials.gov for more information. For information on zinc, vitamin C, and vitamin D see the “Treatments of Interest” chart, above.

Are heartburn drugs effective for treating or preventing COVID-19?

For information on famotidine, see the “Treatments of Interest” chart, above.

Does nicotine protect against COVID-19?

In China, there was an unexpectedly low prevalence of smoking among patients hospitalized with COVID-19. Low smoking prevalence among hospitalized COVID-19 patients has also been seen in the U.S.56

Nicotine, through its cholinergic agonist activity, blocks production of inflammatory cytokines such as IL-6.56

There is interest in using nicotine, either as currently available products, or perhaps via nebulization, as an adjunct for COVID-19 treatment.56

Continue to use nicotine replacement products for nicotine users who are hospitalized for COVID-19, and for anyone who desires to quit smoking.56


Levels of Evidence

In accordance with our goal of providing Evidence-Based information, we are citing the LEVEL OF EVIDENCE for the clinical recommendations we publish.

Level

Definition

Study Quality

A

Good-quality patient-oriented evidence.*

  1. High-quality RCT
  2. SR/Meta-analysis of RCTs with consistent findings
  3. All-or-none study

B

Inconsistent or limited-quality patient-oriented evidence.*

  1. Lower-quality RCT
  2. SR/Meta-analysis with low-quality clinical trials or of studies with inconsistent findings
  3. Cohort study
  4. Case control study

C

Consensus; usual practice; expert opinion; disease-oriented evidence (e.g., physiologic or surrogate endpoints); case series for studies of diagnosis, treatment, prevention, or screening.

*Outcomes that matter to patients (e.g., morbidity, mortality, symptom improvement, quality of life).

RCT = randomized controlled trial; SR = systematic review [Adapted from Ebell MH, Siwek J, Weiss BD, et al. Strength of Recommendation Taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. Am Fam Physician 2004;69:548-56. http://www.aafp.org/afp/2004/0201/p548.pdf.]

Project Leader in preparation of this clinical resource (360423): Melanie Cupp, Pharm.D., BCPS; Last modified June 5, 2020.

References

  1. Product monograph for Kevzara. Sanofi Genzyme. Mississauga, ON L4W 4V9. August 2019.
  2. Gautret P, Lagier JC, Parola P, et al. Hydroxychloroquine and azithromycin as a treatment of COVID-19: results of an open-label, non-randomized clinical trial. Int J Antimicrob Agents 2020 Mar 20:105949. doi: 10.1016/j.ijantimicag.2020.105949.
  3. Gao J, Tian Z, Yang X. Breakthrough: chloroquine phosphate has shown apparent efficacy in treatment of COVID-19 associated pneumonia in clinical studies. BioSci Trends 2020;14:72-3.
  4. FDA. Fact sheet for health care providers emergency use authorization (EUA) of chloroquine phosphate supplied from the strategic national stockpile for treatment of COVID-19 in certain hospitalized patients. https://www.fda.gov/media/136535/download. (Accessed March 31, 2020).
  5. NIH. National Center for Complementary and Integrative Health. In the news: coronavirus and “alternative” treatments. https://www.nccih.nih.gov/health/in-the-news-coronavirus-and-alternative-treatments. (Accessed March 28, 2020).
  6. Cortegiani A, Ingoglia G, Ippolito M, et al. A systematic review on the efficacy and safety of chloroquine for the treatment of COVID-19. J Crit Care 2020 Mar 10. doi: 10.1016/j.jcrc.2020.03.005.
  7. Bermejo-Martin JF, Kelvin DJ, Eiros JM, et al. Macrolides for the treatment of severe respiratory illness caused by novel H1N1 swine influenza viral strains. J Infect Dev Ctries 2009;3:159-61.
  8. Ko WC, Rolain JM, Lee NY, et al. Arguments in favour of remdesivir for treating SARS-CoV-2 infections. Int J Antimicrob Agents 2020 Mar 6:105933. doi: 10.1016/j.ijantimicag.2020.105933.
  9. Beeching NJ, Fletcher TE, Fowler R. Coronavirus disease 2019 (COVID-19). BMJ Best Practice. https://bestpractice.bmj.com/topics/en-gb/3000168/management-approach. (Accessed March 26, 2020).
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  11. CDC. Interim clinical guidance for management of patients with confirmed coronavirus disease (COVID-19). Page last reviewed March 30, 2020. https://www.cdc.gov/coronavirus/2019-ncov/hcp/clinical-guidance-management-patients.html. (Accessed April 2, 2020).
  12. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet 2020;395:507-13.
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  14. Canadian Cardiovascular Society. Guidance from the CCS COVID-19 Rapid Response team. March 20, 2020. https://www.ccs.ca/images/Images_2020/CCS_CHFS_Update_COVID__CV_medications_Mar20.pdf. (Accessed March 27, 2020).
  15. Cao B, Wang Y, Wen W, et al. A trial of lopinavir-ritonavir in adults hospitalized with severe COVID-19. N Engl J Med 2020 Mar 18. doi: 10.1056/NEJMoa2001282.
  16. Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Intern Med 2020 Mar 13. doi: 10.1001/jamainternmed.2020.0994.
  17. Chu CM, Cheng VC, Hung IF, et al. Role of lopinavir/ritonavir in the treatment of SARS: initial virological and clinical findings. Thorax 2004;59:252-6.
  18. Matos RI, Chung KK. DoD COVID-19 practice management guide. Clinical management of COVID-19. March 23, 2020.
  19. Anon. New treatment approach proposed for respiratory distress in COVID-19. Drug Topics. March 26, 2020. https://www.drugtopics.com/clinical-news/new-treatment-approach-proposed-respiratory-distress-covid-19. (Accessed March 28, 2020).
  20. FDA. FDA advised patients on use of non-steroidal anti-inflammatory drugs (NSAIDs) for COVID-19. March 19, 2020. https://www.fda.gov/drugs/drug-safety-and-availability/fda-advises-patients-use-non-steroidal-anti-inflammatory-drugs-nsaids-covid-19. (Accessed March 28, 2020).
  21. Health Canada. No scientific evidence that ibuprofen worsens COVID-19 symptoms. March 20, 2020. https://healthycanadians.gc.ca/recall-alert-rappel-avis/hc-sc/2020/72633a-eng.php. (Access March 28, 2020).
  22. Yang X, Yu Y, Xu J, et al. Clinical course and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a single-centered, retrospective, observational study. Lancet Respir Med 2020 Feb 24. doi: 10.1016/S2213-2600(20)30079-5.
  23. Melville NA, Nainggolan L. Are warnings against NSAIDs in COVID-19 warranted? March 17, 2020. https://www.medscape.com/viewarticle/926940. (Accessed March 28, 2020).
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Cite this document as follows: Clinical Resource, COVID-19 and Pharmacotherapy. Pharmacist’s Letter/Prescriber’s Letter. April 2020.

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