There are no data on the clinical efficacy of the preparation containing sodium aminodihydrophthalazindione in «cytokine storm», including in patients with COVID-19. Protocols of planned or ongoing clinical trials of a preparation containing sodium aminodihydrophthalazindione at COVID-19 have not been found. The use of sodium aminodihydrophthalazindione in the treatment of COVID-19 is possible only in clinical trials.

The routine use of bromhexine to prevent infection SARS-CoV-2 is not recommended. The use of bromhexine is possible in clinical trials.

Until clinical trials of efficacy and safety are obtained, routine use of barycytinib in patients with COVID-19 cannot be recommended.

Routine clinical use of riamilovir in COVID-19 is not recommended. The use of riamilovir is possible in clinical trials.

Hospitalized patients with COVID-19 who have not previously received DOAK by it is not advisable to prescribe POAC for the prevention of thrombosis in patients with COVID-19 due to the lack of clinical trial results, significant potential interactions.

No robust evidence proving clinical effectiveness of methylprednisolone in acute respiratory distress-syndrome in COVID-19, including combined use with tocilizumab, has been identified. Systemic glucocorticosteroids use may be considered acceptable in such patients in life-threatening situations, when interleukin-6 blockers (tocilizumab, sarilumab) are unavailable.

No scientific evidence for the negative influence of angiotensin II receptor blockers onto COVID-19 clinical course has been identified so far. Prescribing angiotensin II receptor blockers as COVID-19 pathogenetic therapy could only be considered within clinical trials. Patients who have been taking angiotensin II receptor blockers for approved indications should continue to do so.

Hyaluronidase is currently not included into Russian or foreign guidelines on the treatment of acute respiratory distress-syndrome in patients with COVID-19, and such treatment is not supported by evidence of clinical effectiveness. Hyaluronidase can only be used for COVID-19 within clinical trials.

No published trials measuring effectiveness of tofacitinib in COVID-19 have been identified. Some professional associations recommend discontinuing tofacitinib if SARS-CoV-2 infections is detected. Taken into account possible complications of the use of tofacitinib (infections, lymphopenia, venous thromboembolism), routine use of tofacitinib cannot be recommended unless within clinical trials under supervision of qualified healthcare professionals.

Impaired kidney function may influence pharmacokinetics of most of the drugs, including the ones used in COVID-19. In this publication, the most important pharmacokinetic parameters and dose adjustment approaches are provided, based on The Renal Drug Handbook и Sanford Guide. In the majority of cases, mild kidney function reduction does not necessitate dose adjustment. Each case should be considered individually, measuring benefits against risks.

Some guidelines describe combined use of hydroxychloroquine and lopinavir/ritonavir as one of the treatment alternatives for severe COVID-19, yet this treatment is not preferable. It requires careful consideration of possible interactions with other drugs, monitoring of cardiotoxicity (including QT-interval measurement), and hepatotoxicity (measurement of ASAT/ ALAT).

Use of canakinumab in patients with COVID-19 is currently lacking proper evidence base, and should not be recommended outside of clinical trials.

Taking recent publications into account, one should consider avoiding routine use of hydroxychloroquine, especially if combined with azithromycin, for COVID-19. Such treatment may be associated with the increased risk for hospital mortality and QT prolongation, while there is no documented effectiveness regarding SARS-CoV-2 clearance and outcomes. This treatment may be considered in individual cases, provided potential benefit and risks are carefully weighted, and safety monitoring is enhanced. Hydroxychloroquine safety in outpatients with COVID-19 is poorly studied and risks are increased by challenges in monitoring QT and electrolytes, hence hydroxychloroquine cannot be considered as first line treatment in outpatient settings. Such use of hydroxychloroquine is not recommended if clinical, instrumental, and laboratory monitoring are not in place.

The use of anakinra cannot be currently recommended outside of clinical trials as pathogenetic treatment of “cytokine storm” in severe COVID-19.

We present anticoagulant outpatient deprescribing algorithm in patients with COVID-19 discharged from the hospital. It is reasonable to continue the treatment should the patient have indications for therapeutic anticoagulation. Enhanced prophylaxis of venous thromboembolic complications should be considered in patients with high thromboembolic risk and low risk of bleeding.

Routine clinical use of olokizumab in COVID-19 is not recommended. The use of olokizumab is possible in clinical trials.

There exist some theoretical premises for the use of colchicine in patients with COVID-19, and clinical trials are underway. There is currently no published evidence confirming effectiveness and safety of colchicine in COVID-19 and allowing to recommend it for general practice. If prescribing colchicine, the one should perform clinical and hematological monitoring and avoid drug interactions.

At the time of print, the evidence for using umifenovir in COVID-19 is mainly theoretical. The published clinical trials have contradicting results. The decision to use umifenovir in COVID-19 should be individualized, considering the “experimental” nature of this treatment.

There currently exists no published robust data which would confirm effectiveness and safety of hydroxychloroquine in pre- and postexposure prophylaxis of SARS-CoV-2 infection. Taking into account in vitro data, which indicates inhibitory activity of hydroxychloroquine against SARS-CoV-2, and interim guidelines by the Ministry of Health of the Russian Federation, hydroxychloroquine can be considered as postexposure prophylaxis among healthcare personnel who have been in contact with patients with laboratory confirmed SARS-CoV-2, provided no contraindications and significant drug interactions are present. Safety monitoring should be performed before prescribing and during the course of treatment (ECG, total blood count and blood biochemistry, ophthalmologist evaluation before long-term treatment).

There is currently no evidence for vitamin D3 effectiveness for COVID-19 treatment and prevention.

The use of hydroxychloroquine for COVID-19 treatment and prevention should be restricted in both out- and inpatient settings due to the lack of evidence for effectiveness and unfavorable safety profile.

Current use of dipyridamole in COVID-19 is mainly based on its antithrombotic activity, since there is no robust clinical effectiveness data. The decision to use dipyridamole in COVID-19 should be individualized, considering the experimental nature of this treatment.

Dexamethasone may be used for mortality reduction in patients with severe COVID-19

There are prerequisites for the use of remdesivir against SARS-CoV-2 in stationary conditions. Remdesivir is not registered in the Russian Federation. The preliminary results of randomized clinical trials on the efficacy of remission are contradictory.

Currently, the use of mefloquine in patients with COVID-19 does not have sufficient scientific justification and, given the unfavorable efficacy and safety profile, cannot be considered for routine use in clinical practice.

There are experimental and clinical data regarding the activity of favipiravir against the SARS-CoV-2 virus. The is evidence of significant variability in pharmacokinetics and associated achievement of the required inhibitory concentration of the drug. The evidence base for the effectiveness of use in patients with mild to moderate COVID-19 is limited to open-label randomized clinical trials. The use of the drug, given the limited experience of using favipiravir, requires special attention to the safety of its prescription (pregnancy test, contraception compliance, control of uric acid, transaminases, ECG). At present, the prescription of the drug can be considered by the attending physicians if the expected benefits of its use prevail over the possible risks in accordance with the approved instructions for medical use and the temporary guidelines of the Ministry of Health of Russia.

Global experience with the clinical use of favipiravir is very limited. Its safety is for further study. Prevention of teratogenic effects (mandatory pregnancy test before starting therapy, compliance with effective contraception by both women and men), control of the level of uric acid, transaminases and ECG are of fundamental importance. Alertness is needed for new, insufficiently documented or previously unreported adverse events such as motor disturbances and falls. Patients should be fully informed about all the risks of therapy before starting it. Special attention is required to timely fill out the approved forms of notifications on the development of HP and report them in time according to the Order of the Federal Service for Surveillance in Healthcare of February 15, 2017 No. 1071 «On approval of the Procedure for the implementation of pharmacovigilance.»

Introduction. In a crisis, like the COVID-19 outbreak, the strategy of experimental drug use in clinical practice increases the availability of potentially effective drugs that have not yet proven the opposite for patients with life-threatening diseases, despite the fact that such use is «off-label» for unregistered indications. The choice of drugs for «off-label» use is most difficult when a large potential benefit justifies higher risks, because the use of drugs for unapproved indications increases the frequency of adverse drug reactions and thereby reduces their clinical value. Goal. Clinical and pharmacological analysis of the «off-label» features of drug use for etiotropic and pathogenetic therapy of COVID-19, description of new opportunities for state registration of medicines in the fight against a new coronavirus infection. Materials and methods. From the Russian temporary guidelines for the treatment of COVID-19 were identified 14 international non-generic names (INN) of drugs. We analyzed the data obtained for the corresponding INN in the State register of medicines of the Ministry of health of the Russian Federation. Results. There is a widespread violation of the requirements of various sections of the current instructions for the medical use of the considered drugs, which requires additional analysis of real-word data. Conclusions. For this purpose, we can use thematic reports, patient registers, and active post-marketing pharmacovigilance.