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1. COVID-19
MEDICATIONS

2. 2
3
1 Antiviral Therapy
Adjunctive Therapy
Immune – Based
Therapy
OUTLINES

3. Antiviral
Therapy

4. Antiviral Therapy
Remdesivir
Remdesivir binds to the viral RNA-dependent RNA polymerase, inhibiting
viral replication through premature termination of RNA transcription.
It has been studied in several clinical trials for the treatment of COVID-19.
It is available through the Food and Drug Administration (FDA)
Emergency Use Authorization (EUA) for people
with severe COVID-19.

5. Remdesivir COVID-19 Emergency Use Authorization Expanded
Remdesivir was FDA-approved for the treatment of coronavirus disease
2019 (COVID-19) in hospitalized adult and pediatric patients (≥12 years of
age and weighing ≥40 kg).
The emergency use (EUA) authorization continues to allow for remdesivir
(lyophilized powder only) to be used by licensed health care providers for
the treatment of suspected or laboratory-confirmed COVID-19 in
hospitalized pediatric patients weighing ≥3.5 kg.
Antiviral Therapy
Remdesivir

6. Monitoring
Baseline and during remdesivir administration when clinically
appropriate:
Hepatic function tests (ALT, AST, bilirubin, alkaline
phosphatase, prothrombin time)
Renal function tests (serum creatinine, CrCl)
Hematology
Signs/symptoms of infusion reaction.
Antiviral Therapy
Remdesivir

7. Adverse Effects
Elevated transaminase levels (avoid use if ALT ≥5 times the ULN)
Increase in prothrombin time (without a change in the INR).
Gastrointestinal symptoms (e.g., nausea, vomiting)
Antiviral Therapy
Remdesivir

8. Hepatic impairment
Baseline hepatic impairment:
There are no dosage adjustments provided in the manufacturers
labeling (has not been studied)
Hepatoxicity during therapy:
ALT >10 times the ULN.
ALT elevation and signs or symptoms of liver inflammation.
Increase in conjugated bilirubin, alkaline phosphatase or INR
DC
Antiviral Therapy
Remdesivir

9. Renal impairment
eGFR ≥30 mL/minute: No dosage adjustment necessary
eGFR <30 mL/minute: No formal safety or pharmacokinetic
data are available.
Remdesivir contains renally cleared
sulfobutylether-beta-cyclodextrin sodium
(SBECD) which accumulates in patients
with kidney dysfunction.
Antiviral Therapy
Remdesivir

10. Hypersensitivity
Infusion-related and anaphylactic reactions
Slowing infusion rate (maximum infusion time: 120 minutes)
may be considered to potentially prevent these reactions.
Discontinue administration and institute appropriate treatment
if a clinically significant hypersensitivity reaction occurs.
Antiviral Therapy
Remdesivir

11. Drug – drug interactions
Concomitant Use With Chloroquine or Hydroxychloroquine
The FDA is warning health care providers that co-administration of
remdesivir and chloroquine phosphate or hydroxychloroquine sulfate is not
recommended as it may result in reduced antiviral activity of remdesivir.
Health care providers should review the most up-to-date fact sheet when
prescribing remdesivir.
Last access October 31th 2020
Antiviral Therapy
Remdesivir

12. Drug – drug interactions
Clinical drug-drug interaction studies of remdesivir have not been
conducted.
patients should remain under close observation during the days of remdesivir
administration
In vitro, remdesivir is metabolized by enzymes CYP2C8, CYP2D6, and CYP3A4, P-
glycoprotein (P-gp).
Strong inhibitors may result in increased remdesivir exposure.
The use of strong inducers (e.g. rifampicin) may decrease plasma
concentrations of remdesivir and is not recommended
Antiviral Therapy
Remdesivir

13. Pregnancy
The safety and effectiveness have not been evaluated in
pregnant patients.
Only when the potential benefit justifies the potential risk to
the mother and the fetus.
Remdesivir should not be withheld from pregnant patients if it
is otherwise indicated.
Last access October 31th 2020
Antiviral Therapy
Remdesivir

14. Restricted Form
Antiviral Therapy
Remdesivir

15. Antiviral Therapy
CQ & HCQ
Recommendations
The COVID-19 Treatment Guidelines Panel (the Panel) recommends against the use
of chloroquine or hydroxychloroquine with or without azithromycin for the
treatment of COVID-19 in hospitalized patients (AI).
In non-hospitalized patients, the Panel recommends against the use of chloroquine
or hydroxychloroquine with or without azithromycin for the treatment of COVID-19,
except in a clinical trial (AI).
The Panel recommends against the use of high-dose chloroquine (600 mg twice
daily for 10 days) for the treatment of COVID-19 (AI).

16. Antiviral Therapy
CQ & HCQ
Despite demonstrating antiviral activity in some in vitro
systems, hydroxychloroquine with or without azithromycin
did not reduce upper or lower respiratory tract viral loads or
demonstrate clinical efficacy in a rhesus macaque model.
An emergency use
authorization (EUA) Revoked

17. Antiviral Therapy
CQ & HCQ
Rationale
Hydroxychloroquine did not decrease 28-day mortality when compared to
the usual standard of care.
Longer median hospital stay.
Persons treated with HCQ who were not on mechanical ventilation at
baseline were more likely to be placed on mechanical ventilation during
follow up.
More adverse events
Increased risk of QT prolongation among patients treated with HCQ
compared to those not receiving HCQ

18. Antiviral Therapy
CQ & HCQ
Adverse Effects
QTc prolongation, Torsade de Pointes, ventricular arrythmia, and
cardiac deaths.
Baseline and follow-up electrocardiograms are recommended when
there are potential drug interactions with concomitant medications
(e.g., azithromycin) or underlying cardiac diseases.
The risk-benefit ratio should be assessed for patients with cardiac
disease, a history of ventricular arrhythmia, bradycardia (<50 bpm),
or uncorrected hypokalemia and/or hypomagnesemia.
Hypoglycemia, rash, and nausea.
Hydroxychloroquine has fewer and
less severe toxicities (including less
propensity to prolong the QTc
interval) and fewer drug-drug
interactions than chloroquine.

19. Antiviral Therapy
CQ & HCQ
Drug-Drug Interactions
Azithromycin
QTc interval
prolongation
Multiple studies: prolongation of QTc
interval.
The use of HCQ plus azithromycin was
associated with increased odds of
cardiac arrest.
The use of this combination warrants
careful monitoring.
Major – Generally Avoid
Major
CQ: C- Moderate risk –
Monitor
HCQ: B – No action needed
ECG monitoring
Serious – Use alternative
Avoid (HCQ)
Caution / Monitor (CQ)

20. Antiviral Therapy
CQ & HCQ
Drug-Drug Interactions
Anti-diabetic
agents
May enhance the hypoglycemic
effect of Hypoglycemia
associated agents.
Cardiac Glycosides
Aminoquinolines
(Antimalarial) may increase
the serum concentration of
Cardiac Glycosides.
X
Medications that
pose a moderate
to high risk for QTc
prolongation. Antiarrhythmics
Antipsychotics
Fluoroquinolone.

21. Antiviral Therapy
Ivermectin
Recommendation
The COVID-19 Treatment Guidelines Panel recommends
against the use of ivermectin for the treatment of COVID-19,
except in a clinical trial.
PK and PD studies suggest that achieving the plasma
concentrations necessary for the antiviral efficacy detected in
vitro would require administration of doses up to 100-fold
higher than those approved for use in humans.

22. Antiviral Therapy Lopinavir/Ritonavir
Recommendation
The COVID-19 treatment Guidelines Panel recommends
against using lopinavir/ritonavir or other HIV protease
inhibitors for the treatment of COVID-19,
except in a clinical trial.

23. Antiviral Therapy Lopinavir/Ritonavir
Rationale
The PDof lopinavir/ritonavir raise concerns about whether it is
possible to achieve drug concentrations that can inhibit the
SARS-CoV-2 proteases.
In addition, lopinavir/ritonavir did not show
efficacy in a moderately sized randomized
controlled trial in patients with COVID-19.

24. Antiviral Therapy Lopinavir/Ritonavir
Adverse Effects
Nausea, vomiting, diarrhea (common)
Nearly 14% of lopinavir/ritonavir recipients were unable to complete the full
14-day course of administration due primarily to gastrointestinal adverse
events, including anorexia, nausea, abdominal discomfort, or diarrhea, as
well as two serious adverse episodes of acute gastritis.
QTc prolongation
Hepatotoxicity

25. Antiviral Therapy Lopinavir/Ritonavir
Warnings/Precaution
Concerns related to adverse effects:
May alter cardiac conduction and prolong the QTc and/or PR interval;
second- and third-degree AV block and torsade de pointes have been
observed.
Use with caution in patients with underlying structural heart disease,
preexisting conduction system abnormalities, ischemic heart disease or
cardiomyopathies.
Avoid use in combination with QTc- or PR-interval prolonging drugs or in
patients with hypokalemia or congenital long QT syndrome.

26. Antiviral Therapy Lopinavir/Ritonavir
Warnings/Precaution
Concerns related to adverse effects:
May cause hepatitis and/or exacerbate pre-existing hepatic dysfunction;
use with caution in patients with underlying hepatic disease, such as
hepatitis B or C, cirrhosis, or unspecified hepatic impairment.
Consider more frequent liver function test monitoring during therapy
initiation in patients with preexisting hepatic dysfunction.

27. Antiviral Therapy Lopinavir/Ritonavir
Warnings/Precaution
Disease-related concerns:
Diabetes: Changes in glucose tolerance, hyperglycemia, exacerbation of
diabetes, DKA, and new-onset diabetes mellitus have been reported in
patients receiving protease inhibitors.
Hepatic impairment: Use with caution; lopinavir concentrations may be
increased.
Pancreatitis: Use with caution in patients with increased triglycerides;
pancreatitis has been observed.

28. Antiviral Therapy Lopinavir/Ritonavir
Monitoring
HIV antigen/antibody testing at baseline
Serum transaminase levels
Triglycerides and cholesterol
Consider monitoring ECG when LPV/RTV is
given with other QTc-prolonging medications.

29. Antiviral Therapy Lopinavir/Ritonavir
Renal impairment
There are no dosage adjustments (has not been studied); however, a
decrease in clearance is not expected.
Hemodialysis: Avoid once-daily dosing in hemodialysis patients.
Hepatic impairment
Mild to moderate impairment: There are no dosage adjustments; however,
lopinavir is primarily metabolized by the liver and its AUC may be increased
~30%; use with caution.
Severe impairment: There are no dosage adjustments (has not been
studied); use with caution.

30. Antiviral Therapy Lopinavir/Ritonavir
Drug – drug interaction
Apixaban
Atorvastatin
Rosuvastatin
Cilostazol
Digoxine
Garlic

31. Immune
Based
Therapy

32. Immune – Based
Therapy
Human
blood-
derived
products
Immunom
odulatory
agents

33. Immune – Based
Therapy
There are insufficient data to recommend either for or against the
use of the following :
COVID-19 convalescent plasma,
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
immunoglobulins.
The Panel recommends against the use of the following (except in a
clinical trial)
Mesenchymal stem cells (AII)
Non-SARS-CoV-2-specific intravenous
immunoglobulin (IVIG) (AIII)
Human blood-
derived products

34. Immune – Based
Therapy Convalescent Plasma
Currently, there are insufficient data from well-
controlled, adequately powered, randomized clinical
trials to evaluate the efficacy and safety of
convalescent plasma for the treatment of COVID-19.
The guideline panel continues to recommend
COVID-19 convalescent plasma only in the context
of a clinical trial

35. Immune – Based
Therapy Convalescent Plasma
CP donor requirements:
Eligible donors include:
Individuals who have had symptoms of COVID-
19 and a positive result with a diagnostic test for
COVID-19 that has been approved, cleared, or
authorized by the FDA
Individuals who have not had a positive COVID-
19 diagnostic test or symptoms of COVID-19, but
who have a positive test for SARS-CoV-2
antibodies using two different tests approved,
cleared or authorized by the FDA.
or

36. Immune – Based
Therapy Convalescent Plasma
CCP donor requirements:
Other donor requirements include:
 Complete resolution of symptoms at least 14 days
prior to donation (a negative diagnostic test for
COVID-19 is not required to qualify).
 Must meet all other requirements for standard
whole blood collection including testing for
infectious disease; additional requirements must
be met if plasma is collected by apheresis.

37. Immune – Based
Therapy Convalescent Plasma
Existing data suggests that if a benefit
exists, CP is most useful when given early
(particularly when administered within 72
hours of COVID-19 diagnosis.) and with a
high titer of neutralizing antibodies.

38. Immune – Based
Therapy Convalescent Plasma
Adverse effects
The available data suggest that serious
adverse reactions following the
administration of COVID-19 convalescent
plasma are infrequent and consistent with
the risks associated with plasma infusions
for other indications.

39. Immune – Based
Therapy Convalescent Plasma
Adverse effects
These risks include:
Transfusion-transmitted infections (e.g.: [HIV],
hepatitis B, hepatitis C)
Allergic reactions, anaphylactic reactions
Hemolytic reactions.
Hypothermia
Metabolic complications
Post-transfusion purpura

40. Immune – Based
Therapy
Human
blood-
derived
products
Immunom
odulatory
agents

41. Immune – Based
Therapy
In the early days of the SARS-CoV-2 pandemic, based on experience in both
SARS and MERS, recommendations cautioned against the use of systemic
corticosteroids due to risk of worsening clinical status, delayed viral
clearance, and adverse events.
The Randomised Evaluation of COVID-19 Therapy (RECOVERY) trial, a
multicenter, randomized, open-label trial in hospitalized patients with
COVID-19, showed that the mortality from COVID-19 was lower among
patients who were randomized to receive dexamethasone than among
those who received the standard of care also the duration of mechanical
ventilation.
Corticosteroids

42. Immune – Based
Therapy
Warnings/Precautions
Cardiovascular disease: Use with caution in patients with heart failure and/or
hypertension; use has been associated with fluid retention, electrolyte
disturbances, and hypertension. Monitor BP.
GI disease: Use with caution in patients with GI diseases due to GI perforation
risk. Signs of GI perforation may be masked in patients receiving
corticosteroid therapy.
Renal impairment: Use with caution in patients with renal impairment; fluid
retention may occur.
Corticosteroids

43. Immune – Based
Therapy
Warnings/Precautions
Hepatitis B virus reactivation: Detection of chronic or past HBV infection
requires a risk assessment to determine antiviral prophylaxis requirements,
monitoring, and follow up.
Psychiatric disturbances: including depression, euphoria, insomnia, mood
swings, personality changes, severe depression to psychotic manifestations.
Preexisting psychiatric conditions may be exacerbated by corticosteroid use.
Diabetes: may alter glucose production/regulation leading to hyperglycemia.
May require addition or adjustment of antidiabetic therapy.
Corticosteroids

44. Immune – Based
Therapy
Warnings/Precautions
Adrenal suppression: particularly in younger children or in patients receiving
high doses for prolonged periods or with chronic use.
Withdrawal and discontinuation of a corticosteroid should be done slowly
and carefully.
Seizure disorders: Use corticosteroids with caution in patients with a history
of seizure disorder; seizures have been reported with adrenal crisis.
Discontinuation of therapy: Withdraw therapy with gradual tapering of dose.
Corticosteroids

45. Immune – Based
Therapy
Considerations in Pregnancy
A short course of betamethasone and dexamethasone, which are known to
cross the placenta, is routinely used to decrease neonatal complications of
prematurity in women with threatened preterm delivery.
Given the potential benefit of decreased maternal mortality and the low risk
of fetal adverse effects for a short course of dexamethasone therapy, the
Panel recommends using dexamethasone in hospitalized pregnant women
with COVID-19 who are mechanically ventilated (AIII) or who require
supplemental oxygen but who are not mechanically ventilated (BIII).
Corticosteroids

46. Immune – Based
Therapy
There are insufficient data to recommend for or
against the use of interleukin (IL)-1 inhibitors, such
as anakinra, for the treatment of COVID-19.
Interleukin-1 Inhibitors

47. Immune – Based
Therapy
Renal Impairment
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute or end-stage renal disease (ESRD): Consider
administering the prescribed dose every other day.
Hemodialysis: Not dialyzable (<2.5%)
Hepatic Impairment
There are no dosage adjustments provided in the manufacturer's labeling
(has not been studied).
Interleukin-1 Inhibitors

48. Immune – Based
Therapy
Warnings/Precautions
Infections: Associated with an increased risk of serious infections in
rheumatoid arthritis studies.
Injection site reactions: Injection site reactions commonly occur (within first
4 weeks of therapy) and are generally mild with a duration of 14 to 28 days.
Asthma: Use with caution in patients with asthma; may have increased risk of
serious infection.
Renal impairment: Use caution in patients with renal impairment
Elderly: Use caution due to the potential higher risk for infections
Interleukin-1 Inhibitors

49. Immune – Based
Therapy
Pregnancy Considerations
Information related to the use of anakinra during pregnancy is limited
Anakinra should be discontinued once pregnancy is confirmed
Breast-Feeding Considerations
It is not known if anakinra is present in breast milk.
Adverse events have not been observed in breastfeeding infants following
maternal use of anakinra.
Consider the risk of infant exposure, the benefits of breastfeeding to the
infant, and the benefits of treatment to the mother.
Interleukin-1 Inhibitors

50. Immune – Based
Therapy
Adverse Reactions
Central nervous system: Headache (12% to 14%)
Gastrointestinal: Vomiting
Infection
Local: Injection site reaction
Respiratory: Nasopharyngitis
Miscellaneous: Fever
Interleukin-1 Inhibitors

51. Immune – Based
Therapy
Recommendation
The Panel recommends against the use of anti-IL-6 receptor monoclonal
antibodies (e.g., sarilumab, tocilizumab) or anti-IL-6 monoclonal antibody
(siltuximab) for the treatment of COVID-19, except in a clinical trial (BI).
Rationale
Tocilizumab failed to show or to exclude a beneficial effect on 28-day
mortality compared to no tocilizumab treatment.
Interleukin-6 Inhibitors

52. Immune – Based
Therapy
ALERT: US Boxed Warning
Risk of serious infections: Patients treated with tocilizumab are at
an increased risk for developing serious infections that may lead to
hospitalization or death.
Most patients who developed these infections were taking concomitant
immunosuppressants, such as methotrexate or corticosteroids.
Tocilizumab

53. Immune – Based
Therapy
ALERT: US Boxed Warning
Tuberculosis (pulmonary or extrapulmonary)
Both reactivation of latent infection and new infections have been reported.
Patients should be tested for latent tuberculosis infection before and during
therapy.
Some patients who test negative prior to therapy may develop active
infection; monitor for signs and symptoms of tuberculosis during and after
treatment in all patients.
Tocilizumab

54. Immune – Based
Therapy
Renal Impairment
CrCl ≥30 mL/minute: No dosage adjustment necessary.
CrCl <30 mL/minute: There are no dosage adjustments provided in the
manufacturer's labeling (has not been studied)
Hepatic Impairment
There are no dosage adjustments provided in the manufacturer's labeling
(has not been studied).
Initiation of therapy in patients with active hepatic disease or hepatic
impairment or in rheumatoid arthritis (RA) and giant cell arteritis (GCA)
patients with baseline ALT or AST >1.5 × ULN is not recommended.
Tocilizumab

55. Immune – Based
Therapy
Warnings/Precautions
GI perforation: Use with caution in patients at increased risk for GI perforation
Hematologic effects: Neutropenia and thrombocytopenia may occur. Monitor
neutrophils and platelets. Do not initiate treatment in patients with giant cell
arteritis (GCA), polyarticular juvenile idiopathic arthritis, rheumatoid arthritis
(RA), or systemic juvenile idiopathic arthritis with an ANC <2,000/mm3 or
platelet count <100,000/mm3; discontinue treatment for ANC <500/mm3 or
platelet count <50,000/mm3.
Tocilizumab

56. Immune – Based
Therapy
Warnings/Precautions
Hepatic effects: Hepatic injury, resulting in liver transplant or death, has been
reported. May require treatment interruption, dose or interval modification, or
discontinuation.
Hyperlipidemia: Therapy is associated with increases in total cholesterol,
triglycerides, LDL, and/or HDL.
Hypersensitivity: May cause hypersensitivity or anaphylaxis
Elderly: Infection has been reported at a higher incidence in elderly patients
compared with younger adults; use with caution in elderly patients.
Tocilizumab

57. Immune – Based
Therapy
Drug – drug interaction
Biological disease-modifying antirheumatic drugs (DMARDs):
Concomitant use with other biological DMARDs has not been
studied and should be avoided due to the increased risk of
infection.
Tocilizumab

58. Immune – Based
Therapy
Considerations in Pregnancy
There are insufficient data to determine whether there is a drug-associated
risk for major birth defects or miscarriage. Monoclonal antibodies are actively
transported across the placenta as pregnancy progresses (with greatest
transfer during the third trimester) and may affect immune responses in
utero in the exposed fetus.
Tocilizumab

59. Adjunctive
Therapy

60. Adjunctive Therapy
Low molecular weight heparin or unfractionated heparin may be
preferred in hospitalized, critically ill patients because of their
shorter half-lives, ability to be administered intravenously or
subcutaneously, and fewer drug-drug interactions compared
with oral anticoagulants (AIII).
Antithrombotic Therapy

61. Adjunctive Therapy
Renal Impairment
CrCl >30 mL/minute: No dose adjustment necessary.
CrCl <30 mL/minute:
VTE prophylaxis: SubQ: 30 mg once daily.
VTE treatment: SubQ: 1 mg/kg once daily.
Hepatic Impairment
There are no dosage adjustments provided in the manufacturer's labeling (has
not been studied); use with caution.
Heparins; Enoxaparin

62. Adjunctive Therapy
Dosing: Obesity
VTE prophylaxis: SubQ: BMI ≥40 kg/m2
Initial: 40 mg twice daily .
Some experts suggest 60 mg twice daily in patients with more extreme forms
of obesity (BMI >47 kg/m2)
A weight-based approach can be used: 0.5 mg/kg twice daily (based on actual
body weight)
Heparins; Enoxaparin

63. Adjunctive Therapy
Warnings / Precautions
Bleeding
Hyperkalemia
Thrombocytopenia
Elderly: Use with caution in the elderly; delayed elimination may occur
Low weight patients: Risk of bleeding may be increased in women <45 kg and
in men <57 kg.
Heparins; Enoxaparin

64. Adjunctive Therapy
ALERT: [US Boxed Warning]
Heparins; Enoxaparin
Epidural or spinal hematomas may occur in patients who are anticoagulated
with low molecular weight heparins (LMWH) or heparinoids and are
receiving neuraxial anesthesia or undergoing spinal puncture. These
hematomas may result in long-term or permanent paralysis.

65. Adjunctive Therapy
Monitoring Parameters
Platelet count
Hemoglobin, hematocrit
Fecal occult blood
Signs and symptoms of bleeding
Serum creatinine at baseline and during therapy.
Heparins; Enoxaparin

66. NIH
Lexicomp
EMC
Drugs.com
FDA factsheet Remdesivir
IDSA
Medscape
micromedix
References