Upanib15 mg

Upanib is a selective Janus kinase 1 (JAK1) inhibitor used in adults (and select pediatric populations) for the following conditions, in patients who have had an inadequate response to, or are intolerant of, one or more other systemic therapies (for example, conventional DMARDs or TNF-blocker therapy), per approved labeling:

• Established/FDA-approved indications:
  • Moderate-to-severe active rheumatoid arthritis
  • Active psoriatic arthritis
  • Active ankylosing spondylitis and active non-radiographic axial spondyloarthritis with objective signs of inflammation
  • Moderate-to-severe atopic dermatitis (refractory disease)
  • Moderately-to-severely active ulcerative colitis
  • Moderately-to-severely active Crohn's disease
• Guideline-supported, age-restricted use: Active polyarticular juvenile idiopathic arthritis and juvenile psoriatic arthritis in appropriately selected pediatric patients (see Pediatric Uses).

Upanib is generally used after conventional or biologic therapies have failed or are not tolerated, and is not recommended as first-line therapy in most guidelines. It is not effective as monotherapy for indications that specifically require concomitant methotrexate per local labeling (verify current approved combination requirements with your physician).

Each extended-release tablet contains Upadacitnib INN 15 mg or 30 mg (as the hemihydrate salt, formulated as an extended-release matrix tablet). Strength and available presentations may vary by manufacturer; check the specific product label dispensed.

Upanib is an orally administered, small-molecule, selective Janus kinase 1 (JAK1) inhibitor belonging to the targeted synthetic disease-modifying antirheumatic drug (DMARD) class. By blunting JAK1-dependent cytokine signaling, Upanib reduces the inflammatory cascade implicated in a range of autoimmune and inflammatory conditions, including rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, atopic dermatitis, ulcerative colitis, and Crohn's disease.

Upanib is supplied as an extended-release tablet taken once daily and is generally reserved for patients with an inadequate response to, or intolerance of, other systemic therapies, given its boxed-warning safety profile (see Precautions and Warnings).

Upanib belongs to the Janus Kinase (JAK) inhibitor class — specifically a selective JAK1 inhibitor — categorized as a targeted synthetic disease-modifying antirheumatic drug (tsDMARD) / immunomodulatory agent.

Mechanism

Upadacitnib selectively and reversibly inhibits Janus kinase 1 (JAK1), a key intracellular enzyme in the JAK-STAT signaling pathway. Many pro-inflammatory cytokines involved in autoimmune disease (including IL-6, IL-2, IL-7, IL-15, IL-21, interferons, and others) signal through receptors that depend on JAK1 (often paired with JAK2, JAK3, or TYK2). By inhibiting JAK1-mediated phosphorylation and activation of STAT transcription factors, Upadacitnib down-regulates the transcription of genes driving inflammation, immune cell activation, and tissue damage in conditions such as rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, atopic dermatitis, and inflammatory bowel disease.

Pharmacokinetics

• Absorption: Well absorbed orally; extended-release formulation permits once-daily dosing; can be taken with or without food.
• Metabolism: Primarily hepatic, mainly via CYP3A4, with a minor contribution from CYP2D6.
• Elimination half-life: Approximately 8–14 hours, consistent with once-daily dosing of the extended-release tablet.
• Excretion: Mainly via feces and urine as metabolites and unchanged drug.

• Take Upanib by mouth once daily, at approximately the same time each day, with or without food.
• Swallow the extended-release tablet whole; do not split, crush, or chew it, as this may alter the extended-release properties.
• If a dose is missed, take it as soon as remembered the same day; do not double the dose to make up for a missed one.

Upanib is primarily metabolized by CYP3A4, making it susceptible to clinically significant drug interactions:

• Strong CYP3A4 inhibitors (e.g., ketoconazole, clarithromycin, itraconazole): Increase Upanib plasma concentrations; dose reduction or caution is generally required — consult a physician before co-administration.
• Strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort): Reduce Upanib efficacy by lowering plasma concentrations; concomitant use is generally not recommended.
• Other immunosuppressants (biologic DMARDs, azathioprine, cyclosporine, other JAK inhibitors): Combining with Upanib increases the risk of additive immunosuppression and serious infection; concurrent use is not recommended.
• Live/attenuated vaccines: Should be avoided during Upanib therapy due to the risk of vaccine-related infection in an immunosuppressed host (see Precautions and Warnings).

Common Side Effects

• Upper respiratory tract infections (nasopharyngitis, sinusitis)
• Nausea
• Headache
• Elevated blood creatine phosphokinase (CPK)
• Acne
• Cough
• Fever

Less Common but Serious Side Effects

• Herpes zoster (shingles) reactivation and other herpes viral infections
• Elevated liver enzymes
• Neutropenia, lymphopenia, or anemia
• Elevated lipid levels (LDL/HDL cholesterol)
• Serious infections, malignancy, major adverse cardiovascular events, and thrombosis — see Precautions and Warnings for the boxed-warning risks associated with Upanib.

Patients should seek prompt medical attention for signs of infection (fever, chills, persistent cough), unusual bleeding/clotting symptoms (leg swelling, chest pain, shortness of breath), or unexplained weight loss or lumps while taking Upanib.

Pregnancy: Human data on Upanib use in pregnancy are limited. Based on animal reproduction studies and its mechanism of action, Upanib may cause fetal harm and is generally not recommended during pregnancy. Upanib should be used in pregnancy only if clearly needed and if the potential benefit to the mother justifies the potential risk to the fetus; always consult a physician before use if pregnant or planning pregnancy. Women of reproductive potential are generally advised to use effective contraception during treatment and for a period after the last dose, per product labeling — confirm the specific duration with the prescribing physician.

Lactation: It is not known whether Upanib passes into human breast milk. Because of the potential for serious adverse reactions in a nursing infant, a decision should be made to discontinue breastfeeding or discontinue Upanib, taking into account the importance of the drug to the mother; consult a physician before breastfeeding while on Upanib.

Boxed Warning

Upanib, like other drugs in the JAK inhibitor class, carries a boxed warning for increased risk of:

• Serious infections leading to hospitalization or death (including tuberculosis, invasive fungal, bacterial, and viral infections, and opportunistic infections)
• All-cause mortality (including sudden cardiovascular death), observed in comparative studies against TNF blockers
• Malignancy, including lymphoma and non-melanoma skin cancers
• Major adverse cardiovascular events (MACE), including cardiovascular death, myocardial infarction, and stroke
• Thrombosis, including deep vein thrombosis, pulmonary embolism, and arterial thrombosis

These risks appear particularly elevated in patients 50 years of age and older with at least one additional cardiovascular risk factor; Upanib should generally be reserved for patients with an inadequate response or intolerance to one or more TNF blockers in these higher-risk groups, per approved labeling.

Additional Precautions

• Screen for latent/active tuberculosis and viral hepatitis (B and C) before starting Upanib; treat latent TB before initiation.
• Monitor lipid profile periodically after starting Upanib, as elevations in LDL and HDL cholesterol may occur.
• Monitor complete blood count (neutrophils, lymphocytes, hemoglobin) and liver function periodically during treatment.
• Avoid live/attenuated vaccines during treatment; update vaccinations per current immunization guidelines prior to starting Upanib.
• Interrupt Upanib if a serious infection, opportunistic infection, or sepsis develops, until the infection is controlled.
• Use with caution in patients with risk factors for gastrointestinal perforation (e.g., diverticulitis).

There is limited clinical experience with Upanib overdose. In case of a suspected overdose, seek immediate medical attention or contact a poison control center/emergency services. Management should include general supportive care and close monitoring of vital signs and clinical status; there is no specific antidote for Upanib. Do not attempt to manage a suspected overdose at home.

Store at room temperature (below 30°C), away from light and moisture. Keep out of reach of children.

Renal Impairment

No dose adjustment is needed for mild-to-moderate renal impairment. In severe renal impairment, use the lowest effective dose of Upanib with close monitoring; Upanib has not been studied in end-stage renal disease.

Hepatic Impairment

No dose adjustment is required in mild hepatic impairment. Use the lowest effective dose in moderate hepatic impairment. Upanib is not recommended in patients with severe hepatic impairment.

Elderly

Patients 65 years of age and older, and particularly those 50 years and older with at least one cardiovascular risk factor, are at higher risk of the serious adverse effects described in the boxed warning (infections, malignancy, MACE, and thrombosis); use Upanib with caution in this population and only when alternative therapies are inadequate or not tolerated.

Pediatric

See Pediatric Uses for age-specific approved indications and dosing; safety and efficacy of Upanib have not been established in all pediatric age groups or indications.

Duration of Upanib therapy depends on the indication and clinical response. For ulcerative colitis and Crohn's disease, induction dosing is given for a fixed period (8 weeks for ulcerative colitis, 12 weeks for Crohn's disease) before transitioning to maintenance dosing; if adequate response is not achieved by the end of the induction period, discontinuation should be considered. For rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis, and atopic dermatitis, Upanib is typically continued long-term at the lowest effective dose as long as benefit is demonstrated and no safety concerns arise, with periodic reassessment by the treating physician given the drug's boxed-warning risk profile.

Janus Kinase (JAK) Inhibitors; Selective JAK1 Inhibitors; Targeted Synthetic Disease-Modifying Antirheumatic Drugs (tsDMARDs)

Upadacitnib works by selectively and reversibly inhibiting Janus kinase 1 (JAK1), an intracellular enzyme central to the JAK-STAT signaling pathway used by numerous pro-inflammatory cytokines. By blocking JAK1-dependent phosphorylation of STAT proteins, Upadacitnib interrupts the downstream transcription of inflammatory mediators, thereby reducing immune cell activation and inflammation in autoimmune and inflammatory conditions such as rheumatoid arthritis, psoriatic arthritis, spondyloarthritis, atopic dermatitis, and inflammatory bowel disease.

Use of Upanib in pediatric patients is limited to specific, age-defined approved indications:

• Polyarticular juvenile idiopathic arthritis and juvenile psoriatic arthritis: approved for use in children 2 years of age and older, with weight-based dosing per approved labeling.
• Atopic dermatitis: approved for adolescents 12 years of age and older with refractory moderate-to-severe disease.

Safety and efficacy of Upanib have not been established in children below these approved age thresholds, or for indications (such as rheumatoid arthritis, ulcerative colitis, and Crohn's disease) where pediatric data are not established. Pediatric use should only be initiated and monitored by a physician experienced in treating pediatric autoimmune/inflammatory disease, with the same infection, malignancy, cardiovascular, and thrombosis precautions applied as in adults.