Upadacitinib

Indications

Upadacitinib is used for: Rheumatoid Arthritis

Adult Dose

Rheumatoid Arthritis Indicated for moderately to severely active rheumatoid arthritis in adults who have had an inadequate response or intolerance to methotrexate 15 mg PO qDay May be used as monotherapy or in combination with methotrexate or other nonbiological DMARDs Hepatic impairment Mild or moderate (Child-Pugh A or B): No dose adjustment required Severe (Child-Pugh C): Not recommended

Child Dose

Renal Dose

Renal impairment Mild, moderate, or severe: No dose adjustment required ESRD: Not studied

Administration

Contra Indications

Precautions

Malignancies reported; consider risks and benefits of treatment before initiating in patients with known malignancy, other than previously treated nonmelanoma skin cancer; screen for malignancies during treatment according to guidelines Thrombosis reported, including DVT, PE, and arterial thrombosis Gastrointestinal perforation reported; unknown if JAK inhibition is implicated in these events; many patients were also receiving NSAIDs May cause neutropenia, lymphopenia, anemia, elevated lipids, or elevated liver enzymes; monitor for abnormal laboratory values and assess the need to interrupt dosing Based on findings in animal studies, may cause fetal harm when administered to pregnant women

Pregnancy-Lactation

Pregnancy Limited human data on use in pregnant women are not sufficient to evaluate a drug-associated risk for major birth defects or miscarriage Verify pregnancy status of females of reproductive potential before starting treatment Animal data Based on animal studies, upadacitinib has the potential to adversely affect a developing fetus In animal embryofetal development studies, oral upadacitinib administration to pregnant rats and rabbits at exposures greater or equal than ~1.6 and 15 times the maximum recommended human dose (MRHD), respectively, resulted in dose-related increases in skeletal malformations (rats only), an increased incidence of cardiovascular malformations (rabbits only), increased postimplantation loss (rabbits only), and decreased fetal body weights in both rats and rabbits Contraception Females of reproductive potential: Use effective contraception during treatment and for 4 weeks after final dose Clinical considerations Published data suggest that increased disease activity is associated with risk of developing adverse pregnancy outcomes in women with rheumatoid arthritis Adverse pregnancy outcomes include preterm delivery (before 37 weeks of gestation), low birth weight (less than 2500 g) infants, and small for gestational age at birth Lactation No data available on the presence of upadacitinib in human milk, the effects on the breastfed infant, or the effects on milk production Available data in animals have shown upadacitinib excreted in milk If a drug is present in animal milk, it is likely the drug will be present in human milk Because of the potential for serious adverse reactions in the breastfed infant, advise patients that breastfeeding is not recommended during treatment with upadacitinib, and for 6 days (~10 half-lives) after the last dose

Interactions

Adverse Effects

Side effects of Upadacitinib : >10% Upper respiratory tract infection (13.5%) 1-10% Nausea (3.5%) Neutropenia (1.1-2.4%) Lymphopenia (0.3-2.4%) Cough (2.2%) Elevated ALT (0.8-2.1%) Increased creatine phosphokinase (0.3-1.6%) Elevated AST (1-1.5%) Pyrexia (1.2%) <1% Pneumonia Herpes zoster Herpes simplex (includes oral herpes) Oral candidiasis Anemia (<0.1%)

Mechanism of Action

Janus kinase-1 (JAK1)-selective inhibitor; JAK1 is essential for signaling for certain cytokines to elicit signals from various interleukins, cardiotrophin, neurotrophin, and interferons These signals are essential in maintaining the inflammatory condition in rheumatoid arthritis (RA); inhibition of JAK reduces production of and modulates proinflammatory cytokines central to RA