Steroids
Use of steroids like methylprednisolone, hydrocortisone, dexamethasone or prednisolone also plays a very important role.
Steroids therapy in COVID 19 severe infection with respiratory distress leading to hypoxia on oxygen inhalation or on ventilator support –
Dexamethasone 6 mg per day for up to 10 days or until hospital discharge, whichever comes first.
Alternative steroids therapies are
- Prednisone 40 mg
- Methylprednisolone 32 mg
- Hydrocortisone 160 mg
- Frequency varies according to their half lives.
- Long half life (36 – 72 hours)-dexamethasone; so need to be given once daily.
- Intermediate half life (12 – 36 hours)- prednisone and methylprednisolone; administer once daily or in two divided doses daily.
- Short half life (8 – 12 hours)- hydrocortisone; administer in two to four divided doses daily.
Remdesivir
Till now the data though not statistically significant suggest that in patients who were on remdesivir showed lower mortality and faster recovery rate. It’s a broad-spectrum antiviral.It’s a nucleotide analog prodrug.
- Dose in adults – a single dose of 200 mg infused intravenously over 30-120 minutes first day subsequently once-daily maintenance dose of 100 mg, same administration method. for 4 days.
- To be diluted in 250 mL 0.9% saline and infuse over 30 to 120 minutes
- Duration is 5 days to 10 days. (Data comparing 5 days versus 10 days courses show similar outcomes). In patients with severe illness on ventilator or ECMO support 10 days of therapy is under trials.
Adverse effects
- Hepatitis
- Increase prothrombin time.
- Acute kidney injury over underlying chronic kidney disease.
Children
Also there are similar data (with positive results but not statistically significant) on use in children with severe disease requiring support of ventilators and or ECMO support.
Pregnancy
It is used in pregnancy with good outcomes.
Renal Impairment
In patients especially with low glomerular filtration rate (GFR) (less than 30 ml/min) there are many side effects. Patients with eGFR greater than or equal to 30 mL/min are reported to have received remdesivir for treatment of COVID-19 with no dose adjustment of remdesivir.
It’s active ingredient that is sulfobutylether-β-cyclodextrin sodium salt (SBECD) cleared from kidneys and it’s concentration increases in patients with renal failure, administration of drugs formulated with SBECD (such as remdesivir) is not recommended in adults.
Remdesivir is being used in severe suspected and confirmed cases of COVID-19 infection. But for renal failure data related to safety of its use is not available. thus it is still unknown. Also in dialysis and post kidney transplant patients there is no data available.
Drug interactions with remdesivir
Use of chloroquine and hydroxychloroquine (HCQS) with remdesivir is not recommended. with chloroquine or hydroxychloroquine. There is a potential reduction of antiviral activity of remdesivir because of chloroquine or hydroxychloroquine. The vitro data confirmed the antagonistic effect of chloroquine on the intracellular metabolic activation and antiviral activity of remdesivir.
Antithrombotic therapy
Not required in non hospitalised patients. Also not to be given post discharge from hospital.
Indicated in hospitalised patients as prophylaxis per protocol of Venous thromboembolism (VTE).
Therapeutic doses of antithrombotics in following-
- In cases with incident VTE or clinically highly suspicious of VTE
- Patients on ECMO, on dialysis with dialysis catheters
Azithromycin
Azithromycin is an antibiotic drug that helps fight the bacteria. It is used to treat various types of infections which are caused by bacteria like respiratory infections, skin and other infections.
If there is a history of hepatitis post azithromycin it’s use should be avoided.
Also history of allergic to drugs like clarithromycin, erythromycin, or
telithromycin.
To make sure that one is safe taking this drug one has to tell the doctor if ever had –
- liver disease
- kidney disease
- myasthenia gravis
- a heart rhythm disorder
- low levels of potassium in your blood or
- long QT syndrome (family history is also important)
What should not be taken if one is having azithromycin –
Not to take any antacids that contain aluminium or magnesium before or after 2 hours of taking azithromycin.
Renal Dose Adjustments
Moderate to mild renal dysfunction (CrCl greater than 10 mL/min): adjustment is not recommended.
Severe renal dysfunction (CrCl less than 10 mL/min): to be used with caution.
In dialysis patients dose is not confirmed
Hydroxychloroquine sulfate (HCQS)
HCQS tablets constitute 200 mg hydroxychloroquine sulfate, equivalent to 155 mg base.
HCQS is indicated for the treatment of chronic discoid lupus erythematosus and systemic lupus erythematosus in adults.
It’s use is doubtful. Rather recently studies have shown no benefit and it should not be used in COVID 19 infection.
Also if used with azithromycin there can be further prolongation of Qtc.
Dose in COVID 19 800 mg PO once on Day 1, subsequently 400 mg PO once daily for 4–7 days. Duration of treatment is still not confirmed.
Adverse effects
- Prolonged QTc interval, arrhythmia
- GIT effects (e.g., nausea, vomiting, diarrhea)
- Increase liver enzymes
- Low sugars
- Myopathy
- Neuropsychiatric effects
- Allergic reactions
Renal dysfunction: No adjustment recommended.
Dialysis : Data not available
Vitamin C
Recommended daily dose of vitamin C for adults and children of age more than 4 years is 60 mg. Can be increased to 90 mg/ day in the normal population.
There is insufficient data suggesting use of vitamin c in COVID 19 infection.
For prevention for COVID 19 200 mg of vitamin C daily or 1-2 grams daily for COVID-19 treatment.
For maintenance hemodialysis (MHD) patients advise supplementation with ascorbic acid 75-90 mg daily to replace the losses of this water-soluble vitamin that occur during dialysis.
Vitamin C is renal excreted, intake more than 200 mg/day should be avoided in kidney failure to avoid oxalosis. Oxalosis is the accumulation of the metabolic by-product of ascorbic acid. Many organs and body tissues are affected by oxalate deposits, including the kidneys.
Large doses may cause a buildup of oxalate in people with kidney disease. Accumulation of oxalate in the bones and soft tissue, which can cause severe pain in muscles, bones and other issues over time.
Nitazoxanide
It is an antiparasitic agent for managing cryptosporidiosis and giardiasis, both parasites that cause diarrhea, as well as used against anaerobic bacteria, viruses, and other protozoa. However, it does show some in vitro activity, against the influenza virus and other coronaviruses, as well as rotaviruses, and the hepatitis B and C viruses. Finally it is still under trials for prevention and early treatment.
Ivermectin
Ivermectin, an antiparasitic drug, also used for covid 19 treatment. Dose is not confirmed. In most centres it is used as 12 mg single dose or for 5 days.
Some have been used as 200 mcg/kg single dose then can repeat after 7 days.
It can cause severe neurotoxicity.
For Renal failure and dialysis patients : Dose is not confirmed
Instruction for usage
To be taken before meals with a full glass of water.
Recently studies showed a high-fat meal absorption was significantly higher than in the fasting.
Interleukin inhibitors
Immunomodulators are being tried, they have antiinflammatory effects as because of cytokine release there is inflammation leading to severe pneumonia. Interleukin (IL) inhibitors, Janus kinase (JAK) inhibitors , and interferons are used in many trials..
IL inhibitors help in managing severe lung injury caused by cytokine release in patients with severe COVID-19 infections. A “cytokine storm” with release of various interleukins with tumour necrosis factor alpha (TNFα) and other inflammatory mediators.
Interleukin-6 inhibitors
Tocilizumab is an IL-6 inhibitor. IL-6 is a pleiotropic proinflammatory cytokine secreted by many types of cells like lymphocytes, monocytes, and fibroblasts. SARS-CoV-2 infection causes a dose-dependent production of IL-6 from bronchial epithelial cells.