COVID-19: Guidelines of drugs for home therapy situations

An annotated guide to the Guidelines for Home Treatment of SARS-CoV-2 infections - by Dr Carla Bruschelli

A summary to the Guidelines for Home Treatment of SARS-CoV-2 infections - by Dr Carla Bruschelli

This article is a translation from the original post COVID-19: i farmaci per la terapia domiciliare, done by our partners from esanum.it. You can also visit the German translation of this article by our partners at esanum.de.

Dr. Carla Bruschelli, a General Practitioner specialising in Internal Medicine and Pharmacology, has summarised the main guidelines on COVID-19 home therapy issued until late November by the World Health Organization (WHO), the US' National Institutes of Health (NIH) and the UK’s National Institute for Health and Care Excellence (NICE). The tables below are intended as an aid to colleagues involved in patient care but are also an invitation to continually update their knowledge and clinical practice using appropriate tools to improve the quality of the patient care we provide.

Medicine is an evolving practice based on the scientific method

At the end of 2019, an unknown and highly contagious virus appeared in China, causing severe pneumonia in patients that required intensive treatment. Within a few weeks, the whole world, and primarily the scientific community, was confronted with a novel virus and disease, which in its severe forms was difficult to treat and for which there was no effective therapy.

On 31 December 2019, Chinese authorities announced an outbreak in Wuhan, China, of a pneumonia from an unknown agent that was eventually isolated by Chinese scientists by 9 January 2020. On 12 February 2020, the International Committee on Taxonomy of Viruses (ICTV) assigned the virus the name SARS-CoV-2.

Almost two years later, knowledge about the virus and the disease has increased. Diagnostic and therapeutic protocols have been developed. Above all, effective vaccines have been developed that can reduce, and in many cases eliminate, the effects of infection. Considerable progress has been made, but there is certainly still a long way to go.

The first months of the pandemic, at the beginning of 2020, were characterised by uncertainties, and the first therapeutic interventions were based on empirical knowledge. From the therapeutic point of view, the recommendations of the international monitoring institutions followed a cautious evolution, pending the results of the various studies that had been activated. At that time, there was an attempt from several corners of the world to shatter the cardinal principles of the scientific method, especially the experimental verification of the hypotheses formulated, all following the belief that “if it worked with my patient, it´ll work on others”. One thinks, for example, of the cases of chloroquine and hydroxychloroquine, or that of hyperimmune plasma. If this was understandable, though not justifiable, in the early 2020s, this is totally unacceptable today.

International and national guidelines for the treatment of SARS-CoV-2 infection are now based on solid studies and increasingly robust evidence. While still in flux, they represent a valuable tool for the management of COVID-19 patients. And at present, the only scientifically valid one.

In the Italian context (as in many other parts of the world), especially regarding home-based care, the phenomenon of administering therapy that does not comply with the guidelines and recommendations for COVID-19 patients is still alive. So much so that, in a quasi-organised way, committees have been set up to support home care for COVID-19 patients that all too often may have no scientific basis, and may also disregard basic principles of drug administration, including in-depth knowledge of the patient or the importance of a caring relationship between physicians and their patients.

In order to contribute to patient care during the ongoing pandemic, and to allow our colleagues to stay up-to-date on latest COVID-19 care and clinial practice developments, the tables below hope to create an easy-to-access format on the available scientific information.

Medications used at home for SARS-CoV-2 infection

DRUG / ACTIVE COMPONENT	WHO	NIH	NICE	Min/AIFA*
NSAIDS	yes	yes	yes	yes
Coxibs	n.e.	n.e.	n.e.	n.e.
Systemic corticosteroids	only with ↓PO₂	no	only with ↓PO₂	no
Inhaled corticosteroids	yes	yes	n.e.	yes
Antithrombotic drugs (heparin)	only high risk	only high risk	only high risk	only high risk
Antibiotics	no	no	only if bacterial risk	no
Immunosuppressants (hydroxychloroquine)	no	no	no	no
Immunomodulators (colchicine)	no	no	no	no
Antiparasitics (ivermectin)	no	no	no	no

n.e.: not evaluated

Supplements used at home for SARS-CoV-2 infection

SUPPL.	WHO	NIH	NICE	Min/AIFA
Vitamin C	n.e.	no	n.e.	no
Vitamin D	no	no	no	no
Zinc	n.e.	no	n.e.	no
Lactoferrin	n.e.	n.e.	n.e.	no
Quercetin	n.e.	n.e.	n.e.	n.e.
Resveratrol	n.e.	n.e.	n.e.	n.e.

n.e.: not evaluated

The person comes before the disease

It is crucial to remember that in the treatment of any health problem that may require pharmacological intervention, the administration of any drug or active ingredient requires an assessment of the individual and not just of a phenomenon such as a pathology/problem. Each administration must consider age, body weight and adipose tissue, sex, pre-existing pathologies and therapies, patient compliance, and general risk factors.

A complex issue such as the novel coronavirus therefore requires a correct and individual management, while considering the options available in the choice of validated drugs and those included in the recommendations. This to optimise results by reducing the possible occurrence of unwanted effects or ADRs and obtaining control of the inflammatory condition underlying the etiopathogenetic mechanism of the COVID-19 disease. The use of antibiotics, inhaled steroids, systemic steroids, and antithrombotic drugs should only be justified by the suspected or established presence of specific complications during infection.

In this respect, the family physician is certainly the person who, by making use of his or her individual, longitudinal and family knowledge of a patient, can guarantee observation and a capacity for targeted intervention with faster resolution of the condition associated with the viral infection. In this sense, a more in-depth knowledge of the characteristics of individual active ingredients can be a winning factor in achieving treatment objectives; reducing doses according to gender, age, weight, or choosing to avoid interactions with other drugs already taken by the patient, considering the metabolism of the drug to choose mode of intake and time, evaluating possible occurrence of allergic reactions or adverse effects, is what we hope will guide the physician in the appropriate choice of individual treatment.

Data sheets of treatments included and excluded in the main guidelines for Sars-CoV-2 infection management

Treatments used off label and in the absence of literature data in the home treatment of SARS-CoV-2 infection

Personalised Medicine

After considering all the aspects of home treatment, to conclude and confirm what has been examined, the recent Vademecum (in Italian language only) for the care of the person with SARS-CoV-2 infection of the SIMIT (Italian Society of Infectious and Tropical Diseases) reiterates in a concise manner that pharmacological treatments aimed at attacking the disease induced by SARS-CoV-2 infection are and remain hospital-based, consisting of antiviral drugs (Remdesivir), monoclonal antibodies (Casirivimab/imdevimab, Bamlanivimab/etesevimab and Sotrovimab) and biotechnological drugs (Tocilizumab, Anakinra, Baricitinib).

An additional observation is the recommendation to treat patients with COVID-19 with gastric protectants, if indicated by previous history or clinical conditions predisposing to gastroduodenal bleeding during disease.

In the light of all this, could we at least acknowledge that the pandemic has led physicians to the most complex of clinical practice, that of personalised medicine and tailor-made treatments? We hope that it can be an expression of rebirth, resilience, and even cultural and methodological growth, especially for local-scale medicine.

PARACETAMOL
Indications	Treatment of pain and fever
Spectrum of activity	CNS
Adult dosage	500 mg, 1 g
Posology	Minimum intervals of 8 hours at a dose of 1gr, 6 hours at lower doses In pregnancy: doses of 500 mg
Pharmacodynamics	Action on CNS opioid system and inhibition of prostaglandins (PGs)
Pharmacokinetics	Hepatic metabolism 98%, renal metabolism 2% Rapid absorption
Interactions	Rifampicin Phenobarbital Carbamazepine CAF regime Anticoagulants
Undesirable side effects or adverse drug reactions	Overdose: renal tubular necrosis, acute liver failure
Contraindications	Creatinine Clearance <10ml/min Gilbert's disease G6PHD deficiency Alcohol use disorder (AUD)

KETOPROFENE
Indications	Treatment of inflammatory states associated with pain In paediatrics, also treatment of fever
Spectrum of activity	Central Nervous System (CNS) Prostaglandins (PGs) Quinine
Adult dosage	40 mg, 80 mg
Posology	Minimum intervals of 8 hours
Pharmacodynamics	NSAID derivative of propionic acid, PG inhibitor and interaction with quinines, analgesic action, including central analgesic, anti-inflammatory, antipyretic
Pharmacokinetics	Renal metabolism, half-life of 6 hours, plasma peak at 2 hours
Interactions	NSAIDS Anticoagulants Lithium SSRIs ACE inhibitors Steroids Diuretics Beta-blockers Sulphonamides Antiplatelet drug (antiaggregant) Methotrexate (MTX)
Undesirable side effects or adverse drug reactions	Gastrointestinal bleeding (GI bleed) Arterial thrombosis Severe skin reactions Hypertransaminasemia Bronchospasm Acute hepatitis Kidney failure Fertility impairment Diarrhoea Drowsiness Vertigo
Contraindications	NSAID allergy Third trimester pregnancy Peptic ulcers (gastric or duodenal) Ulcerative colitis (UC) (also ulcerative proctitis) Asthma Heart failure Kidney failure Liver failure Thrombocytopenia Leukopenia Smoking

DOXICYCLINE
Indications	Respiratory, urinary, ENT, gynaecological, dermatological, surgical, or gastrointestinal acute infections
Spectrum of activity	Gram+ and Gram- bacteria Mycoplasmas Chlamydia Rickettsia
Adult dosage	100 mg, always taken with plenty of water
Posology	100 mg/24 hours/7-10 days 100 mg/12 hours 200 mg single dose 1st day, followed by 100 mg/24 hours
Pharmacodynamics	Systemic antibacterial, 2nd generation synthetic lipophilic tetracycline, bacteriostatic, inhibits protein synthesis in susceptible bacteria through specific and reversible binding to the 30S ribosomal subunit
Pharmacokinetics	Renal absorption, plasma peak in 2-4 hours, half-life 16-22 hours, 40% renal excretion and 60% faecal excretion
Interactions	Barbiturates Anticoagulants Lithium Methotrexate Cyclosporine Digoxin Penicillins Magnesium-based antacids
Undesirable side effects or adverse drug reactions	Esophageal ulcer Liver failure Kidney failure Urticaria Pericarditis Neutropenia C. difficile–associated diarrhoea (CDAD) Candidiasis Headache Tooth discolouration Photosensitivity
Contraindications	Consumption on an empty stomach Pregnancy Breastfeeding Oesophagitis Gastro-Esophageal Reflux Disease (GERD) Kidney failure Milk and dairy products

AZITHROMYCIN
Indications	ENT, dental, cutaneous, bronchial, and pulmonary infections; urethritis caused by Chlamydia
Spectrum of activity	Gram+ aerobes Gram- facultative aerobe Anaerobes
Adult dosage	500 mg
Posology	500mg/24 hours for 3 days
Pharmacodynamics	Azalide macrolide, inhibits assembly of 50S ribosomal subunits
Pharmacokinetics	Plasma peak 2-4 hours, half-life 2-4 days, biliary excretion
Interactions	Ergotamine Procainamide Amiodarone Sotalol Pimozide Citalopram Quinolones Chloroquine Cyclosporine
Undesirable side effects or adverse drug reactions	QT prolongation C. difficile–associated diarrhoea (CDAD) Heart failure Bradycardia Vomiting Lymphocytopenia Hyperglycaemia Elevated creatinine Hyperpotassemia
Contraindications	Insufficient studies in pregnancy Multi-morbid elderly patients

CEFIXIME
Indications	Acute ENT, urinary, pulmonary and bronchial infections
Spectrum of activity	Clinically significant Gram+ and Gram-
Adult dosage	400 mg
Posology	400mg/24 hours for 7-14 days
Pharmacodynamics	Cephalosporin, inhibits bacterial cell wall synthesis
Pharmacokinetics	Plasma peak 3-4 hours, half-life 4 hours, biliary and renal excretion
Interactions	Warfarin Nifedipine Contraceptives
Undesirable side effects or adverse drug reactions	Severe skin reactions Pseudomembranous colitis Acute kidney failure
Contraindications	Penicillin allergy First trimester pregnancy

LEVOFLOXACIN
Indications	Acute pyelonephritis Complicated urinary tract infections (UTIs) Chronic prostatitis Next, to be used ONLY when other recommended antibacterials are inadequate: COPD exacerbation, including bronchitis Acute bacterial rhinosinusitis (ABRS) Community-acquired pneumonia (CAP) Complicated skin and soft tissue infections Acute cystitis
Spectrum of activity	Gram+ Aerobes - including resistant ones Gram- Aerobes and Anaerobes, including resistant ones Mycoplasma Chlamydia
Adult dosage	500 mg, 750 mg
Posology	500 mg/24 hours for 7-14 days 750 mg/24 hours as an induction dose 1-3 days followed by 500 mg/24 hours
Pharmacodynamics	Synthetic fluoroquinolone, acts on the DNA gyrase and Topoisomerase IV complexes. It penetrates the bronchial mucosa, the fluids of the lining epithelia, alveolar macrophages, lung tissue, skin, prostate, and urine.
Pharmacokinetics	Plasma peak 1-2 hours, half-life 8-14 hours, renal excretion
Interactions	Glibenclamide Insulin Tricyclics Macrolides Antipsychotics Antiarrhythmics Warfarin Cyclosporine
Undesirable side effects or adverse drug reactions	Tendon rupture, especially in the elderly C. difficile–associated diarrhoea Hypoglycaemia Photosensitivity Psychotic reactions QT prolongation Peripheral neuropathy Acute hepatitis Confusion Aortic dissection Hypertransaminasemia Depression Vertigo Skin reactions
Contraindications	G6PHD deficiency Pregnancy Breastfeeding Acute kidney failure Epilepsy Cardiac arrhythmias Paediatric age Tendinopathies

AMOXICILLIN - CLAVULANIC ACID
Indications	Acute ENT and skin infections, pyelonephritis, Community-acquired pneumonia (CAP), COPD flare-ups
Spectrum of activity	Gram+ and Gram- sensitive
Adult dosage	875 mg amoxicillin + 125 mg clavulanic acid
Posology	875 mg + 125 mg every 8 hours for 8-10 days
Pharmacodynamics	Amoxicillin: beta lactam, inhibits enzymes for structuring the bacterial cell wall Clavulanic acid is a beta lactamase structurally related to penicillin and prevents inactivation of amoxicillin
Pharmacokinetics	Plasma peak 1 hour; half-life 1-2 hours; amoxicillin excreted via renal route; clavulanic acid mainly via renal route
Interactions	Allopurinol Anticoagulants Probenecid Mycophenolate (Mycophenolic acid)
Undesirable side effects or adverse drug reactions	Colitis Nausea Acute Kidney Failure (overdose) Urticaria Candidiasis
Contraindications	Allergy to penicillins and cephalosporins Liver failure Mononucleosis (severe rashes)

BUDESONIDE - Nasal Spray
Indications	Seasonal allergic rhinitis (hay fever), perennial allergic and non-allergic rhinitis. Treatment of nasal polyps (NP). Prophylaxis of recurrences of nasal polyposis after polypectomy
Spectrum of activity	Nasal mucosal inflammation
Adult dosage	100 mcg
Posology	100 mcg every 12 hours
Pharmacodynamics	Glucocorticosteroid, inhibits synthesis and release of inflammatory mediators and cytokines, and inhibits immediate allergic response
Pharmacokinetics	Absorption in 1-3 min, plasma peak within 1 hour, half-life 4 hours, hepatic metabolism, urinary excretion
Interactions	Tricyclics Levothyroxine Hypoglycemic drugs
Undesirable side effects or adverse drug reactions	Hyperglycaemia ENT infections Respiratory infections Glaucoma Adrenal crisis Candidiasis Headache Insomnia
Contraindications	Coronary heart disease (CHD) Arterial hypertension Thyrotoxicosis Diabetes Glaucoma Breastfeeding

DEXAMETHASONE
Indications	Inflammatory lung diseases including interstitial diseases (ILDs). Allergies, rheumatic diseases, dermatological diseases, inflammatory eye diseases, gastrointestinal diseases, lymphoma, leukaemia, cerebral oedema, thrombocytopenia, autoimmune hemolytic anemia (AIHA)
Spectrum of activity	Tissues with inflammatory states
Adult dosage	0,5-0,75 mg
Posology	0.5-3 mg per day, 1 to 4 intakes per 24 hours
Pharmacodynamics	Steroid, four to six times more potent than methylprednisolone, six to eight times more potent than prednisone and prednisolone, approximately 35 times more potent than cortisone
Pharmacokinetics	Blood peak 30 min, half-life 3.5 h, liver metabolism
Interactions	NSAIDS Furosemide Thiazide Cyclosporine Diltiazem Ketoconazole Anticoagulants Macrolides Ritonavir Lopinavir
Undesirable side effects or adverse drug reactions	Aside from effects such as in Budesonide (spray): Depression Psychosis Hypocalcaemia Hypertensive crises Hyperparathyroidism (increased PTH) Tachycardia Epigastric pain (epigastralgia) Abdominal pain Peptic ulcer Pancreatitis
Contraindications	Aside from the indications for Budesonide spray: Heart failure Acute liver failure Osteoporosis Systemic infections Pregnancy

ENOXAPARIN
Indications	Treatment of Deep Venous Thrombosis (DVT) and Pulmonary Embolism (PE). Acute coronary syndrome (ACS). Venous thromboembolism (VTE) in surgical patients at moderate and high risk, particularly those undergoing orthopaedic, general or oncological surgery. VTE prophylaxis in non-surgical patients with acute pathology such as heart failure. Respiratory failure, severe infections, rheumatic diseases and reduced mobility.
Spectrum of activity	Coagulation system
Adult dosage	From 2000 a 10000 IU s.c. daily
Posology	Prophylaxis: 2000/4000 IU as a single dose per day Treatment: 100 IU/kg, one or two administrations per day for at least 10 days.
Pharmacodynamics	Anti-Xa/IIa activity Antithrombin III (ATIII)-dependent inhibition of other factors
Pharmacokinetics	Plasma peak 3-5 hours, half-life 7 hours, hepatic metabolism
Interactions	NSAIDS Thrombolytics Antiplatelets Glucocorticoids
Undesirable side effects or adverse drug reactions	Thrombocytopenia Haemorrhages Vasculitis Hyperkalemia Headache Elevated transaminase levels Urticaria
Contraindications	Liver failure Chronic Kidney Failure Bleeding and bleeding risk conditions Mechanical / prosthetic valves Low BMI

ASCORBIC ACID
Indications	Vitamin c deficiency
Spectrum of activity	All tissues
Adult dosage	500 mg, 1000 mg
Posology	500 mg to 2 g per day (the daily requirement for adults is normally 60 mg/day)
Pharmacodynamics	Water-soluble vitamin, reduces cellular oxidation
Pharmacokinetics	Rapid absorption, renal excretion
Interactions
Undesirable side effects or adverse drug reactions	Headache Diarrhoea Nausea
Contraindications	Urinary calculi G6PDH deficiency Haemochromatosis Sideroblastic anaemia

HYDROXYCHLOROQUINE
Indications	Treatment of active and chronic Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE)
Spectrum of activity	Both the anti-rheumatic and antimalarial effects can be explained in relation to the concentration achieved in acid intracellular vesicles and through the increase in their pH
Adult dosage	200 mg
Posology	400 to 600mg /day initial dose and after 4-12 weeks 200-400 mg
Pharmacodynamics	Antimalarial belonging to the 4-aminoquinoline family. Interaction with sulphydryl groups, modulation of enzyme activity, DNA fixation; stabilisation of lysosomal membranes; inhibition of prostaglandin synthesis, chemotaxis of polymorphonucleates and phagocytosis; possible interference with IL-1 production
Pharmacokinetics	Peak in 3-4 hours, hepatic metabolism, terminal half-life 30-50 DAYS, renal excretion
Interactions	Antiarrhythmics Tricyclics Quinolones Macrolides Fluconazole Mefloquine Hypoglycaemic drugs Aminoglycosides Clopidogrel Digoxin Dabigatran Metoprolol
Undesirable side effects or adverse drug reactions	Retinopathy Acute Kidney Failure Hypoglycaemia QT prolongation Myocardial infarction (MI) Heart failure Bradycardia Ventricular arrhythmia Hypokalaemia Depression Neurological disorders Dizziness Headache Nausea Diarrhoea Vomiting
Contraindications	Retinopathy Maculopathy (Mascular Degeneration) GI Diseases Psoriasis G6PDH deficiency Pregnancy Breastfeeding

LACTOFERRIN
Indications	Mild anaemia and mild immune deficiencies
Spectrum of activity	Siderophilin (transferrin), a glycoprotein involved in iron transport and concentrated mainly in the mucous membranes, where it stimulates defences as a constituent of neutrophils
Posology	200 mg/day
Interactions
Undesirable side effects or adverse drug reactions	Diarrhoea Skin rash Lack of appetite Asthenia Constipation
Contraindications

CHOLECALCIFEROL
Indications	Prevention and treatment of proven vitamin D deficiency (e.g. in patients with dietary abnormalities, malabsorption, chronic steroid therapy or anticonvulsants)
Spectrum of activity	All tissues
Adult dosage	750-1000 IU /day
Posology	Prevention: 750-1000 IU/day Treatment: 1000 IU/day
Pharmacodynamics	Fat-soluble vitamin. Increases intestinal absorption of calcium
Pharmacokinetics	Hepatic and subsequent renal hydroxylation, accumulation in muscle and adipose tissue, renal and faecal excretion
Interactions	Thiazide diuretics Digitoxin Magnesium Anticoagulants
Undesirable side effects or adverse drug reactions	Arrhythmia Asthenia Confusion Headache Abdominal pain Vomiting Diarrhoea Urinary calculus Skin rash Acute kidney failure Hypercalcaemia
Contraindications	Hypercalcaemia Hypercalciuria Urinary calculi Kidney failure Sarcoidosis

IVERMECTIN
Indications	Antiparasitic
Spectrum of activity	Intestinal anguillulosis, Lymphatic filariasis, Scabies
Adult dosage	3 mg
Posology	3 mg to 18 mg single intake depending on the treatment of helminths (parasitic worms) or parasites
Pharmacodynamics	Anthelmintics, macrocyclic lactones, causes neuromuscular paralysis of parasites
Pharmacokinetics	Peak plasma at 4 hours, half-life 12 hours, faecal excretion
Interactions
Undesirable side effects or adverse drug reactions	Fever Skin rash Hepatitis Haematuria Asthenia (Weakness) State of agitation Leukopenia Headache Hypotension Diarrhoea Tachycardia Muscle pain
Contraindications	Pregnancy

RESVERATROL
Indications	Inflammatory states or mild deficits of the immune system
Spectrum of activity	Phytotherapeutic, Phenol, produced by plants, including edible ones, for antibacterial and antifungal purposes. It acts by facilitating the production of antioxidant enzymes
Posology	From 300 mg to 1000 mg/day
Interactions	NSAIDS Anticoagulants Antiplatelet drugs Antidepressants
Undesirable side effects or adverse drug reactions	Nausea Diarrhoea Ecchymosis (bruising or purpura)
Contraindications	Pregnancy Breastfeeding