Olumiant, 4 mg 28 pcs

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Indications

The treatment of moderate to severe active rheumatoid arthritis in adult patients with intolerance or inadequate response to treatment with one or more baseline anti-rheumatic drugs.

Olumiant may be used as monotherapy or in combination therapy with methotrexate.

Active ingredient

Composition

active ingredient – baricitinib 4,000 mg;

Excipients – intragranular: Mannitol, microcrystalline cellulose, croscarmellose sodium, magnesium stearate; extragranular – microcrystalline cellulose, croscarmellose sodium, magnesium stearate.

The shell (film): dye mixture pink (85G140009) [polyvinyl alcohol, titanium dioxide, macrogol, talcum, lecithin (soybean), iron oxide red dye].

How to take, the dosage

The decision to prescribe Olumiant should be made by a physician experienced in treating patients with rheumatoid arthritis.

Ingestion.

The drug Olumiant should be taken once a day at any time regardless of meals.

The recommended dose of Olumiant is 4 mg once daily.

The use of a dose of 2 mg once daily is suitable for patients aged 75 years and older, and may also be used in patients with a history of chronic or recurrent infection. A dose of 2 mg once daily may be considered for patients who have achieved sustained control of disease activity after using a dose of 4 mg once daily and for whom dose reduction may be recommended.

The drug should not be started in patients with an absolute lymphocyte count less than 0.5×109/l, in patients with an absolute neutrophil count less than 1×109/l or in patients with a hemoglobin lower than 8 g/dL. Treatment can be started once these values are higher than the values presented.

Patient special groups

Patients with impaired renal function

In patients with a creatinine clearance of 30 to 60 mL/min, the recommended dose of the drug is 2 mg once daily. It is not recommended to use Olumiant in patients with creatinine clearance less than 30 ml/min.

Hepatic impairment

In patients with mild to moderate hepatic impairment, no dose adjustment is required. It is not recommended to use Olumiant in patients with severe hepatic impairment.

Patients taking strong inhibitors of organic anion transporter 3 (OAT3) inhibitors (e.g., probenecid) have a recommended dose of 2 mg once daily.

Patients in the elderly

The clinical experience with baricitinib in patients aged 75 years and older is limited, so the recommended starting dose in patients in this group is 2 mg.

Children

The safety and effectiveness of Olumiant in children under the age of 18 years has not yet been established.

Interaction

Pharmacodynamic interactions

Immunosuppressants

The effect of other drugs on the pharmacokinetics of baricitinib:

Transporters

In vitro, baricitinib is a substrate for organic anion transporters (OAT) 3, P-glycoprotein (Pgp), breast cancer resistance protein (BCRP), and multiple resistance and toxin elimination proteins (MATE) 2-K.

In a pharmacological study, the use of probenecid (an OAT3 inhibitor with a strong inhibitory effect) resulted in an approximately twofold increase in AUC(0-∞) with no change in tmax or Cmax of baricitinib. Consequently, in patients taking OAT3 inhibitors with strong inhibitory activity, such as probenecid, the recommended dose of baricitinib is 2 mg once daily.

Co-administration of the OATZ inhibitors ibuprofen and diclofenac with baricitinib may result in increased exposure of baricitinib. However, the inhibitory activity of ibuprofen and diclofenac against OATZ is not as pronounced as that of probenecid, and therefore no clinically significant interaction is expected.

The combined use of baricitinib with cyclosporine (a Pgp/BCRP inhibitor) or methotrexate (a substrate for several transporters including OATP1B1, OAT1, OAT3, BCRP, MRP2, MRP3 and MRP4 (proteins associated with multiple drug resistance)) had no clinically significant effect on baricitinib exposure.

Cytochrome P450 isoenzymes

Under in vitro conditions, baricitinib is a substrate of the cytochrome CYP3A4 isoenzyme, although less than 10% of the total dose is metabolized by oxidation. In pharmacological studies, the combined use of baricitinib with ketoconazole (a strong CYP3A inhibitor) had no clinically significant effect on the pharmacokinetics of baricitinib.

The combined use of baricitinib with fluconazole (a moderately active CYP3A/CYP2C19/CYP2C9 inhibitor) or rifampicin (a strong CYP3A inducer) did not result in clinically significant changes in baricitinib exposure.

Drugs affecting the pH of gastric juice

Elevated gastric juice pH with omeprazole had no clinically significant effect on baricitinib exposure.

The effect of baricitinib on the pharmacokinetics of other drugs:

Transporters

Cytochrome P450 isoenzymes

The combined use of baricitinib with CYP3A substrates (simvastatin, ethinylestradiol or levonorgestrel) has not caused clinically significant changes in the pharmacokinetics of these drugs in pharmacological studies.

Special Instructions

Infections

The incidence of infections, particularly upper respiratory tract infections, is higher with baricitinib than with placebo. In previously untreated patients, an increased incidence of infections was noted with combination with methotrexate compared to baricitinib monotherapy. In patients with active, chronic or recurrent infections, a careful assessment of the benefit/risk ratio of Olumiant is recommended before initiating therapy.

In case of infection, close monitoring of the patient should be ensured and if the patient does not respond to standard therapy, it is recommended to temporarily discontinue Olumiant. The use of Olumiant should not be resumed until the infection is resolved.

Tuberculosis

Patients should be screened for tuberculosis before starting Olumiant. Olumiant is not recommended for use in patients with an active form of tuberculosis. Patients with the latent form of tuberculosis who have not previously received treatment should consider the possibility of anti-tuberculosis therapy before starting therapy with Olumiant.

Deviations of normal laboratory values

According to clinical data, less than 1% of patients had the following changes of blood values: absolute neutrophil count was less than 1 x 109 / L, absolute lymphocyte count was less than 0.5 x 109 / L and hemoglobin less than 8 g/dL. It is not recommended to start therapy or the drug should be temporarily discontinued in case of decrease of neutrophil number less than 1 x 109 / L, decrease of lymphocyte number less than 0.5 x 109 / L or decrease of hemoglobin less than 8 g/dL.

Elderly patients with rheumatoid arthritis have an increased risk of developing lymphocytosis. There is evidence of rare cases of lymphoproliferative disease.

Reactivation of viral infection

In clinical trials, cases of viral reactivation have been reported, including reactivation of herpes virus (e.g., herpes zoster, herpes simplex).

Cases of herpes zoster were more frequently observed in patients aged 65 years and older who had previously been treated with biologic and traditional baseline anti-rheumatic drugs. If a patient develops herpes zoster, the use of Olumiant should be temporarily discontinued until the disease resolves.

In accordance with clinical guidelines before initiating therapy with Olumiant patients should be screened for viral hepatitis. Patients with signs of active hepatitis B or C have not been included in clinical trials. Patients who had hepatitis C virus antibodies but no hepatitis C virus RNA were allowed to participate in clinical trials. Patients with antibodies to hepatitis B virus surface and core antigens and no hepatitis B virus surface antigens were also allowed to participate; hepatitis B virus DNA expression should be monitored in such patients. If hepatitis B virus DNA is detected, the patient should be referred to a hepatologist to determine whether therapy should be continued or discontinued.

Vaccination

Lipids

Elevated liver transaminase concentrations

In clinical trials, increases in ALT and ACT concentrations of 5-fold or greater and 10-fold or greater compared to HGH were reported in less than 1% of patients. When combined therapy with methotrexate was used, an increased frequency of increased concentration of liver transaminases was noted in patients who had not previously received treatment compared to baricitinib monotherapy. If ALT or ACT elevation is detected during examination of patients and drug-induced liver damage is suspected, the use of Olumiant should be temporarily discontinued until this diagnosis is excluded.

Malignant neoplasms

Patients with rheumatoid arthritis have an increased risk of malignant neoplasms, including the risk of lymphoma. Use of immunomodulatory drugs may increase the risk of malignancies, including the risk of lymphoma.

There are insufficient clinical data to estimate the incidence of possible malignancy after baricitinib use. Long-term safety assessment studies are ongoing.

Thromboembolism

Laboratory monitoring

Table 1. Laboratory parameters and monitoring guidelines

Laboratory Indicators

Monitoring Guideline

Synopsis

Contraindications

– Hypersensitivity to the active ingredient or any excipient of the drug

– Pregnancy

– Breast-feeding period

– Childhood under 18 years of age (due to lack of efficacy and safety data)

– Renal failure with a CKR less than 30 mL/min

– Severe hepatic failure

– Age over 75 years

– Active, chronic or recurrent infections (including tuberculosis)

– Decreased neutrophil count (less than 1×109/l), decreased lymphocyte count (less than 0.5×109/l), decreased hemoglobin (less than 8 g/dL)

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– Active hepatitis B and C virus

– Concurrent use of live vaccines

– Patients with risk factors for DVT/TELA

– Combination with biological baseline anti-rheumatic drugs or other Janus kinase inhibitors

– Combination with potent immunosuppressants (e.g., azathioprine, tacrolimus, cyclosporine).

Side effects

The most common adverse reactions that occurred in ≥ 2% of patients taking Olumiant as monotherapy or in combination with basal anti-rheumatic drugs were elevated LDL (33.6%), upper respiratory tract infections (14.7%), and nausea (2.8%). Infections reported with Olumiant included shingles.

The table below shows adverse reactions with frequencies: very common (≥1/10), common (≥1/100 to < 1/10), infrequent (≥1/1000 to < 1/100).

System-organ class

Very often

Often

Infrequent

Infections and invasions

Metabolic and nutritional disorders

Hypercholesterolemiais

Overdose

Pregnancy use

Pregnancy

According to the results of animal studies, the use of high doses of baricitinib can have adverse effects on intrauterine skeletal development.

The use of Olumiant during pregnancy is contraindicated.

Women of childbearing age should use effective contraceptive methods during and for at least 1 week after treatment. If a patient becomes pregnant during the use of Olumiant, she should be informed about the possible risk to the fetus.

Breastfeeding It is not known whether baricitinib (or its metabolites) is excreted with breast milk.

The data of pharmacodynamic/toxicological studies in animals showed that baricitinib is excreted with breast milk.

The risk to newborns/infants cannot be ruled out and therefore Olumiant should not be used during breastfeeding. The benefit of breastfeeding to the baby and of Olumiant to the woman should be evaluated and a decision should be made whether to stop breastfeeding or use Olumiant.