Olumiant (Tablets) Instructions for Use

Marketing Authorization Holder

Swix Healthcare LLC (Russia)

Manufactured By

Lilly Del Caribe, Inc. (Puerto Rico)

Labeled By

LILLY, S.A. (Spain)

ATC Code

L04AA37 (Baricitinib)

Active Substance

Baricitinib (Rec.INN WHO registered)

Dosage Forms

	Olumiant	Film-coated tablets, 2 mg: 14, 28, or 56 pcs.
		Film-coated tablets, 4 mg: 14, 28, or 56 pcs.

Dosage Form, Packaging, and Composition

Film-coated tablets light pink, oblong, engraved with “Lilly” on one side and “2” on the other side.

Excipients: Intragranular mannitol – 52 mg, microcrystalline cellulose – 92 mg, croscarmellose sodium – 6 mg, magnesium stearate – 0.6 mg; extragranular microcrystalline cellulose – 40 mg, croscarmellose sodium – 6 mg, magnesium stearate – 1.4 mg.
Film coating composition pink mixture of dyes (85G140008) – 6 mg (polyvinyl alcohol – 41%, titanium dioxide – 23.6%, macrogol – 18.2%, talc – 16.1%, lecithin (soy) – 0.9%, iron oxide red dye – 0.2%).

14 pcs. – blisters (1) – cardboard packs.
14 pcs. – blisters (2) – cardboard packs.
14 pcs. – blisters (4) – cardboard packs.

Film-coated tablets pink, round, engraved with “Lilly” on one side and “4” on the other side.

Excipients: Intragranular mannitol – 50 mg, microcrystalline cellulose – 92 mg, croscarmellose sodium – 6 mg, magnesium stearate – 0.6 mg; extragranular microcrystalline cellulose – 40 mg, croscarmellose sodium – 6 mg, magnesium stearate – 1.4 mg.

Film coating composition pink mixture of dyes (85G140009) – 6 mg (polyvinyl alcohol – 41%, titanium dioxide – 22.8%, macrogol – 18.2%, talc – 16.1%, lecithin – 0.9%, iron oxide red dye – 1%).

14 pcs. – blisters (1) – cardboard packs.
14 pcs. – blisters (2) – cardboard packs.
14 pcs. – blisters (4) – cardboard packs.

Clinical-Pharmacological Group

Selective immunosuppressant

Pharmacotherapeutic Group

Selective immunosuppressant

Pharmacological Action

Selective and reversible inhibitor of Janus kinase 1 and 2 (JAK1 and JAK2). Baricitinib inhibits the activity of JAK1, JAK2, tyrosine kinase 2, and JAK3 with IC₅₀ (half-maximal inhibitory concentration) values of 5.9, 5.7, 53, and >400 nM, respectively.

Within the intracellular Janus kinase signaling pathway, Janus kinases phosphorylate and activate STATs (signal transducers and activators of transcription), which in turn activate gene expression in the cell. Baricitinib modulates these signaling cascades by partially inhibiting the enzymatic activity of JAK1 and JAK2, thereby reducing the phosphorylation and activation of STAT.

Pharmacokinetics

After oral administration, Baricitinib is rapidly absorbed, with the time to reach C_max being approximately 1 hour (range 0.5-3 hours), and the absolute bioavailability is about 79% (CV = 3.94%). The pharmacokinetics of baricitinib are linear over time.

The mean V_d after intravenous administration is 76 L, indicating distribution of baricitinib into tissues. Approximately 50% of baricitinib is bound to plasma proteins.

The metabolism of baricitinib is mediated by the CYP3A4 isoenzyme, with less than 10% of the dose undergoing biotransformation. Baricitinib metabolites are not detected in plasma. In vitro, Baricitinib is a substrate for the CYP3A4 isoenzyme, organic anion transporter 3 (OAT3), P-glycoprotein (Pgp), breast cancer resistance protein (BCRP), and multidrug and toxin extrusion proteins 2-K (MATE 2-K). Baricitinib may be an inhibitor of organic cation transporters (OCT) 1.

Renal excretion via glomerular filtration and active secretion through OAT3, Pgp, BCRP, and MATE2-K is the primary mechanism of baricitinib clearance. Approximately 75% of the administered dose is excreted by the kidneys, and about 20% via the intestine. In patients with rheumatoid arthritis, the mean clearance and T_1/2 were 9.42 L/h (CV= 34.3%) and 12.5 hours (CV= 27.4%), respectively. The C_max and AUC of baricitinib at steady-state pharmacokinetics in patients with rheumatoid arthritis were 1.4 and 2 times higher, respectively, than in healthy volunteers.

Renal function significantly affects baricitinib exposure. The mean AUC ratios in patients with mild and moderate renal impairment compared to patients with normal renal function were 1.41 (90% CI: 1.15-1.74) and 2.22 (90% CI: 1.81-2.73), respectively. The mean C_max ratios in patients with mild and moderate renal impairment compared to patients with normal renal function were 1.16 (90% CI: 0.92-1.45) and 1.46 (90% CI: 1.17-1.83), respectively.

Indications

Treatment of active moderate or severe rheumatoid arthritis in adult patients with intolerance or inadequate response to one or more disease-modifying antirheumatic drugs.

ICD codes

Dosage Regimen

Take Olumiant orally once daily.

The recommended dose for rheumatoid arthritis is 4 mg.

For patients with moderate renal impairment (CrCl 30 to less than 60 mL/min), reduce the dose to 2 mg once daily.

For patients with severe renal impairment (CrCl less than 30 mL/min), the use of Olumiant is not recommended.

For patients concurrently taking a strong OAT3 inhibitor (e.g., probenecid), reduce the dose to 2 mg once daily.

For patients aged 75 years and older, use with caution; no initial dose adjustment is required.

No dose adjustment is needed for patients with mild or moderate hepatic impairment.

Use with caution in patients with severe hepatic impairment.

Swallow the tablet whole with water; it can be taken with or without food.

Do not initiate therapy if the absolute lymphocyte count (ALC) is less than 0.5 x 10^9/L, the absolute neutrophil count (ANC) is less than 1 x 10^9/L, or hemoglobin is less than 8 g/dL.

Routinely monitor neutrophil, lymphocyte, and hemoglobin levels.

Assess the lipid profile approximately 12 weeks after initiating therapy.

Screen for latent tuberculosis before starting treatment; do not give to patients with active tuberculosis.

Temporarily interrupt treatment if a patient develops a serious infection until the infection is controlled.

Interrupt therapy for herpes zoster until the episode resolves.

Adverse Reactions

Infections and infestations very common – upper respiratory tract infection; common – herpes zoster, herpes simplex, gastroenteritis, urinary tract infection.

Blood and lymphatic system disorders common – thrombocytosis >600×10⁹ cells/L; uncommon – neutropenia <1×10⁹ cells/L.

Metabolism and nutrition disorders very common – hypercholesterolemia; uncommon – hypertriglyceridemia.

Gastrointestinal disorders common – nausea.

Skin and subcutaneous tissue disorders uncommon – acne.

Other common – increased ALT, AST activity; uncommon – weight increased, increased CPK concentration.

Contraindications

Hypersensitivity to baricitinib; pregnancy; breastfeeding period; age under 18 years (due to lack of data on efficacy and safety).

Use in Pregnancy and Lactation

The use of baricitinib during pregnancy is contraindicated.

Baricitinib should not be used during breastfeeding.

Use in Hepatic Impairment

Baricitinib should be used with caution in severe hepatic impairment.

Use in Renal Impairment

Baricitinib should be used with caution in renal impairment (CrCl less than 30 ml/min).

Pediatric Use

The use of baricitinib is contraindicated in patients under 18 years of age.

Geriatric Use

Baricitinib should be used with caution in patients over 75 years of age.

Special Precautions

Baricitinib should be used with caution in renal impairment (CrCl less than 30 ml/min); severe hepatic impairment; active, chronic, or recurrent infections (including tuberculosis); active viral hepatitis B and C; decreased neutrophil count (<1×10⁹/L), decreased lymphocyte count (<0.5×10⁹/L), decreased hemoglobin (<8 g/dL); in combination with biological disease-modifying antirheumatic drugs or other Janus kinase inhibitors; in combination with potent immunosuppressants (e.g., azathioprine, tacrolimus, cyclosporine); concurrent use of live vaccines; patients with risk factors for DVT/PE; patients over 75 years of age.

In patients with active, chronic, or recurrent infections, the benefit/risk ratio of baricitinib use should be carefully assessed prior to initiation of therapy.

Patients should be screened for tuberculosis before starting baricitinib. Baricitinib is not recommended for use in patients with active tuberculosis. In patients with latent tuberculosis who have not been previously treated, the possibility of anti-tuberculosis therapy should be considered before starting baricitinib therapy.

It is not recommended to initiate therapy or baricitinib should be temporarily discontinued in case of a decrease in neutrophil count <1×10⁹/L, a decrease in lymphocyte count <0.5×10⁹/L, or a decrease in hemoglobin <8 g/dL.

In elderly patients with rheumatoid arthritis, the risk of lymphocytosis increases. There are reports of rare cases of lymphoproliferative disorders.

If a patient develops herpes zoster, baricitinib should be temporarily discontinued until the disease resolves.

Patients should be screened for viral hepatitis before starting baricitinib therapy. If hepatitis B virus DNA is detected, the patient should be referred to a hepatologist to determine the possibility of continuing or discontinuing therapy.

The use of live attenuated vaccines during or immediately prior to baricitinib use is not recommended. When considering varicella vaccination before starting baricitinib, international guidelines for vaccination in patients with rheumatoid arthritis should be followed.

The lipid profile should be assessed approximately 12 weeks after starting baricitinib, after which patients should be managed according to international clinical guidelines for the management of patients with hyperlipidemia.

If an increase in ALT or AST activity is detected during patient examination and drug-induced liver injury is suspected, baricitinib should be temporarily discontinued until this diagnosis is ruled out.

Patients with rheumatoid arthritis have an increased risk of malignancies, including the risk of lymphoma. The use of immunomodulatory drugs may increase the risk of malignancies, including the risk of lymphoma.

If clinical signs of DVT/PE are detected, baricitinib should be temporarily discontinued, the patient’s condition should be immediately assessed, and appropriate treatment should be initiated.

Drug Interactions

When baricitinib is used in combination with potent immunosuppressants such as azathioprine, tacrolimus, or cyclosporine, the risk of additive immunosuppression cannot be excluded.

The use of probenecid resulted in an approximately two-fold increase in AUC_(0-∞) without changing the T_max or C_max of baricitinib. Therefore, in patients taking strong OAT3 inhibitors such as probenecid, the recommended dose of baricitinib is 2 mg once daily.

Caution should be exercised when co-administering leflunomide or teriflunomide and baricitinib.

Storage Conditions

Store at 2°C (36°F) to 30°C (86°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.