In our online pharmacy you can buy Baricitinib, a drug for the treatment of COVID-19 under the brand names Barilup, Barikind, Barinat:
- Barilup: One of the few drugs that are employed to treat patients with COVID-19 is Barilup 2mg, combined with the Remdesivir medicine. The Barilup 2mg Tablet is composed from Baricitinib 2mg and is the product of Lupin Ltd.
- Barikind: Produced by Mankind Pharma Ltd, Barikind 4 mg Tablet is used as a treatment for patients with severe rheumatoid arthritis. It is a Janus kinase inhibitor, helping with various symptoms, like tenderness, pain and swelling. Barikind 4 tablet is created through Baricitinib 4mg, which is a JAK inhibitor.
- Barinat: Produced by Natco Pharma Ltd, Barinat 2 and Tablet is used as a treatment for patients with severe rheumatoid arthritis. It is a Janus kinase inhibitor, helping with various symptoms, like tenderness, pain and swelling. Barinat is created through Baricitinib, which is a JAK inhibitor.
Pharmacological action - immunosuppressive. Currently, Baricitinib is actively used to treat coronavirus in the United States, Great Britain, Europe, Australia, Japan and South Korea.
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Mechanism of action
Baricitinib is a selective and reversible inhibitor of Janus kinase 1 and 2 (JAK1 and JAK2). Studies have shown that baricitinib inhibits the activity of JAK1, JAK2, tyrosine kinase-2 and JAK3 with IC50 values of 5.9; 5.7; 53 and> 400 nM, respectively.
Janus kinases (JAKs) are enzymes that transduce intracellular signals from cellular receptors for a number of cytokines and growth factors involved in hematopoiesis, inflammation, and the immune response. As part of the intracellular signaling pathway, JAKs phosphorylate and activate STATs (signal transporters and transcriptional activators), which in turn activate gene expression in the cell. Baricitinib modulates these signaling cascades, partially inhibiting the enzymatic activity of JAK1 and JAK2, thereby decreasing the phosphorylation and activation of STAT.
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Inhibition of IL-6-induced STATS phosphorylation. The use of baricitinib in healthy volunteers led to a dose-dependent inhibition of STAT3 phosphorylation induced by IL-6, with maximum inhibition 2 hours after application and a return to baseline values after 24 hours.
Immunoglobulins. 12 weeks after starting baricitinib, the mean serum IgG, IgM and IgA decreased and remained steadily decreased for at least 104 weeks. In most patients, the change in Ig values was within the normal range.
Lymphocytes. Within 1 week after the start of baricitinib, the mean absolute lymphocyte count increased, but by the 24th week it returned to its initial value and subsequently remained stable for at least 104 weeks. In most patients, the change in the number of lymphocytes was within the normal range.
C-reactive protein. In patients with rheumatoid arthritis, a decrease in the concentration of serum C-reactive protein was observed as early as 1 week after the start of baricitinib use and remained reduced during the entire period of use.
Creatinine. The use of baricitinib led to an increase in serum creatinine concentration by an average of 3.8 μmol / L after 2 weeks of treatment compared with placebo; later this indicator remained stable until the 104th week of treatment. This may be due to inhibition of the secretion of creatinine by baricitinib in the renal tubules. Therefore, the estimate of GFR based on the determination of serum creatinine concentration may be slightly lower without an actual decrease in renal function or the occurrence of adverse renal reactions.
Vaccination. The effect of baricitinib on the humoral response after administration of non-live vaccines (inactivated pneumococcal vaccine or inactivated tetanus vaccine) was studied in a clinical study in patients with rheumatoid arthritis who received baricitinib at doses of 2 and 4 mg. Most of the patients in the study received baricitinib in combination with methotrexate. The results of the study showed that an adequate immune response (IgG) developed in 68% of patients after administration of pneumococcal vaccine and 43.1% of patients after administration of tetanus vaccine.
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After oral administration of baricitinib in the therapeutic dose range, a dose-dependent increase in systemic exposure was observed. The pharmacokinetics of baricitinib are linear over time.
After oral administration, baricitinib is rapidly absorbed, Tmax is approximately 1 hour (range 0.5–3 hours), absolute bioavailability is about 79%. Food intake led to a decrease in baricitinib exposure by 14%, a decrease in Cmax by 18% and an increase in Tmax by 0.5 hours. These changes are not clinically significant.
The average Vd after intravenous administration was 76 liters, which indicated the distribution of baricitinib in the tissues. Approximately 50% of baricitinib binds to plasma proteins.
The metabolism of baricitinib is mediated by the isoenzyme CYP3A4, while less than 10% of the dose received undergoes biotransformation. No metabolites of baricitinib were detected in blood plasma. Pharmacological studies have shown that baricitinib is excreted mainly unchanged by the kidneys (69%) and through the intestines (15%). The kidneys excreted 3 metabolites, through the intestines - 1, their number was, respectively, about 5 and 1% of the administered dose. In vitro, baricitinib is a substrate for the isoenzyme CYP3A4, OAT3, P-gp, BCRP and MATE2-K. Baricitinib can be an OCT1 inhibitor. Baricitinib is not an inhibitor of OAT1, OAT2, OAT3, OST2, OATP1B1, OATP1B3, BCRP, MATE1 and MATE2-K.
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Application of the substance Baricitinib
Active rheumatoid arthritis of moderate or severe degree in adult patients with intolerance or lack of an adequate response to treatment with one or more basic antirheumatic drugs (as monotherapy or in combination therapy with methotrexate), COVID-19 (coronavirus).
How to take and doses
Inside, 1 time per day, at any time, regardless of food intake.
The possibility of using the drug baricitinib in patients with COVID-19, including for the treatment of "cytokine storm"
Indication for medical use of baricitinib, according to the instructions for medical use: treatment of active rheumatoid arthritis of moderate or severe degree in adult patients with intolerance or lack of an adequate response to treatment with one or more basic antirheumatic drugs.
Taking into account the effect of baricitinib on the immune response by disrupting the transduction of intracellular signals from cellular receptors of a number of cytokines (IL-6) and growth factors, the presumptive efficacy of baricitinib in the "cytokine storm" observed in severe COVID-19 is discussed.
Cytokine storm is a cascade, uncontrolled increase in the level of cytokines in the blood, which can lead to an excessive immune response, damage to organs and tissues. It has been established that with COVID-19, lymphohistiocytolysis also occurs, which leads to a cytokine storm, and subsequently to multiple organ failure. In 50% of cases, acute respiratory distress syndrome develops.
How to treat patients with COVID-19 using baricitinib - treatment protocol, treatment regimen
According to the US Department of Health's Interim Guidelines for the Prevention, Diagnosis and Treatment of Novel Coronavirus Infection (COVID-19), version 6 (04/08/2020), as a pathogenetic treatment for moderate pneumonia in order to suppress hyperinflammation and the development of serious lung damage and other organs caused by COVID-19, the administration of the tablet preparation baricitinib (belongs to the group of Janus kinase inhibitors) can be considered as additional therapy (recommended dose: 4 mg once a day for 7-14 days). Baricitinib is included in the treatment regimens for moderate forms of COVID-19 (pneumonia without respiratory failure) in patients over 60 years of age or patients with concomitant chronic diseases:
- Scheme 1: Hydroxychloroquine + azithromycin +/- baricitinib;
- Scheme 2: Mefloquine + azithromycin +/- baricitinib;
- Scheme 3: Lopinavir / ritonavir + recombinant interferon beta-1b +/- baricitinib.
In Yale New Haven Health System's treatment algorithms for COVID-19 patients, baricitinib is included in the list of drugs not recommended as first-line therapy for COVID-19 (but may be considered in some clinical cases after discussion with clinical pharmacologists and treatment specialists infectious diseases). In addition, there is a risk of developing severe infections with the use of baricitinib.