LuciUpa — Upadacitinib 15 mg Tablets, 30 Tabs

LuciUpa is supplied as tablets for oral administration with a precisely calibrated composition of active and inactive components:

• Presentation and Packaging: 1 original sealed plastic bottle made of high-density polyethylene with a tamper-evident, child-resistant cap. Each bottle contains 30 film-coated tablets. The bottle is packaged in a branded cardboard box featuring holographic anti-counterfeiting protection and a package insert.
• Active Ingredient:
  • Upadacitinib — 15 mg per tablet.
• Excipients: Microcrystalline cellulose (filler), hypromellose (extended-release matrix), mannitol, tartaric acid, colloidal anhydrous silica, magnesium stearate, titanium dioxide, macrogol, polyvinyl alcohol, talc, food colorants (yellow iron oxide / red iron oxide).

Pharmacodynamics: Upadacitinib is a selective and reversible inhibitor of the intracellular enzyme Janus kinase 1 (JAK1). Janus kinases are essential cytoplasmic enzymes that transduce cytokine signals from cell surface receptors through the intracellular STAT (Signal Transducer and Activator of Transcription) pathways. By blocking the enzymatic activity of JAK1, upadacitinib prevents the phosphorylation and activation of STAT proteins, interrupting signal transmission of key pro-inflammatory cytokines (IL-2, IL-4, IL-6, IL-7, IL-9, IL-15, IL-21, and type I/II interferons). This leads to a profound suppression of the autoimmune inflammatory cascade.

Pharmacokinetics: Following oral administration, upadacitinib is rapidly absorbed from the gastrointestinal tract. Peak plasma concentration (Cmax) is achieved within 2 to 4 hours. High-fat meals have no clinically significant effect on total systemic drug exposure (AUC). Plasma protein binding is approximately 52%. Metabolism is primarily mediated by the CYP3A4 enzyme with minor involvement of CYP2D6. The drug is eliminated as unchanged upadacitinib and metabolites: approximately 38% via the kidneys and 53% through the intestinal tract. The elimination half-life (T1/2) ranges from 9 to 14 hours.

LuciUpa is indicated for the treatment of the following clinical diagnoses in adult patients (18 years and older):

• 🔹 Rheumatoid Arthritis: Treatment of moderate-to-severe active rheumatoid arthritis in patients who have responded inadequately to or are intolerant of one or more disease-modifying antirheumatic drugs (DMARDs), including methotrexate.
• 🔹 Psoriatic Arthritis: Treatment of active psoriatic arthritis as monotherapy or in combination with non-biological DMARDs.
• 🔹 Ankylosing Spondylitis: Treatment of active ankylosing spondylitis in patients with inadequate response to conventional NSAID therapy.
• 🔹 Non-Radiographic Axial Spondyloarthritis: Treatment of severe axial spondyloarthritis with objective signs of inflammation.
• 🔹 Atopic Dermatitis: Treatment of moderate-to-severe atopic dermatitis in adults and adolescents candidate for systemic therapy.
• 🔹 Ulcerative Colitis and Crohn's Disease: Moderate-to-severe active inflammatory bowel disease in patients with inadequate response or intolerance to biologic therapy or immunosuppressants.

The dosage regimen is prescribed by a specialist physician (rheumatologist, dermatologist, or gastroenterologist) depending on the disease entity:

• 👨‍⚕️ Standard Dosage for Arthritis and Spondyloarthritis:
  • Take 15 mg (1 tablet) once daily, with or without food.
• 👨‍⚕️ For Atopic Dermatitis and IBD (Ulcerative Colitis / Crohn's Disease):
  • The initial or maintenance dose is 15 mg once daily. If clinically necessary and advised by the physician, the dose may be escalated to 30 mg once daily.
• 🥤 Administration Rules: LuciUpa tablets must be swallowed whole with a sufficient amount of water. It is strictly forbidden to chew, crush, or break the tablet, as this disrupts the extended-release profile of the active drug. It is recommended to take the medication at approximately the same time every day.

The use of LuciUpa is strictly contraindicated under the following clinical conditions:

• ❌ Hypersensitivity or known allergy to upadacitinib or any of the inactive ingredients of the tablet.
• ❌ Active severe systemic infections, including active tuberculosis, severe sepsis, or opportunistic infections.
• ❌ Severe hepatic impairment (Child-Pugh Class C).
• ❌ Active viral hepatitis B or C, as well as uncontrolled HIV infection.
• ❌ Pregnancy during all trimesters and the lactation period.
• ❌ Age under 18 years (except for strictly specified atopic dermatitis protocols from 12 years of age as prescribed by a doctor).
• ❌ Severe absolute lymphopenia (<0.5 × 10⁹/L), neutropenia (<1.0 × 10⁹/L), or hemoglobin levels below 80 g/L.

When co-administering LuciUpa with other pharmacological agents, the following factors must be considered:

• ⚠️ CYP3A4 Inhibitors: Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin) increase systemic plasma exposure of upadacitinib. Caution is advised during co-administration.
• ⚠️ CYP3A4 Inducers: Strong CYP3A4 inducers (rifampicin, St. John's wort, phenytoin) decrease upadacitinib concentrations, potentially reducing therapeutic efficacy.
• ⚠️ Immunosuppressants and Biologic DMARDs: Concomitant use of LuciUpa with monoclonal antibodies (infliximab, adalimumab), other JAK inhibitors (tofacitinib, baricitinib), or potent immunosuppressants (cyclosporine, tacrolimus) is not recommended due to the high risk of additive immunosuppression.
• ⚠️ Vaccination: Administration of live or live-attenuated vaccines during LuciUpa therapy is strictly contraindicated.

The use of LuciUpa during pregnancy and lactation is prohibited due to teratogenic risks:

• 🤰 Embryo-Fetal Toxicity: Based on animal studies, upadacitinib exerts embryotoxic and teratogenic effects, causing structural fetal malformations. The drug is contraindicated in pregnant women.
• 🛡️ Contraception: Females of reproductive potential must use effective contraception during treatment with LuciUpa and for at least 4 weeks after receiving the final dose.
• 🤱 Lactation: It is unknown whether upadacitinib is excreted in human milk. Breastfeeding must be completely discontinued during therapy with LuciUpa.

During therapy with LuciUpa, the following adverse drug reactions may occur:

• 🔴 Infections: Upper respiratory tract infections (nasopharyngitis, sinusitis), Herpes zoster (shingles), Herpes simplex, bronchitis, folliculitis, urinary tract infections.
• 🟡 Hematologic & Metabolic: Neutropenia, lymphopenia, anemia, mild hypercholesterolemia, and elevated blood lipid levels.
• 🟠 Gastrointestinal & Hepatic: Nausea, abdominal pain, elevated transaminases (ALT, AST), increased blood creatine phosphokinase (CPK) levels.
• 🟢 Dermatologic: Acne, skin rash, urticaria.
• 🟣 Vascular Risks: Rare cases of deep vein thrombosis (DVT) and pulmonary embolism (PE) in patients with predisposing risk factors.

Clinical manifestations and procedures in case of accidental ingestion of elevated doses:

• Symptoms: In single or repeated overdose of LuciUpa, an exacerbation of the adverse effects listed above may occur, particularly concerning the hematopoietic system and liver enzyme elevations.
• Therapeutic Measures: No specific antidote exists. In case of overdose, monitoring of vital signs, standard procedures to remove unabsorbed drug from the gastrointestinal tract (gastric lavage, administration of activated charcoal), and supportive symptomatic care are recommended.

Rules for storage and transportation of LuciUpa:

• Temperature Range: Store in the original packaging at a temperature not exceeding 30 °C. Do not freeze.
• Protection from Environmental Factors: Keep in the original bottle to protect from moisture and direct sunlight. Keep the bottle tightly closed.
• Storage Safety: Keep out of reach of children and unauthorized persons.
• Shelf Life: 24 months (2 years) from the date of manufacture. Strictly forbidden to use the drug after the expiration date stated on the package.

Criteria for verifying the authenticity of LuciUpa manufactured by Lucius Pharmaceuticals:

• Packaging and Printing: The original carton is made of premium, dense cardboard. The design features a white, blue, and yellow color scheme. The name LuciUpa is printed in a clear, original font without typos.
• Branded Holographic Security Seal: A green security sticker featuring the LUCIUS PHARMACEUTICALS logo, a unique QR code, and a tamper-evident protective layer is affixed to the top flap of the box.
• Factory Markings: The batch number (Batch No.), manufacturing date (Mfg. Date), and expiration date (Exp. Date) are laser-printed on the outer carton and bottle label. The box also displays the "Rx Only" label and contact details for Lucius Pharmaceuticals.