and death Revisions are based on results from completed trial show a higher occurrence of serious heart-related events and cancer in tofacitinib-treated group (both doses) compared to TNF inhibitor-treated group; results also showed an increased risk of blood clots and death with lower doses of tofacitinib Not studied in trials, so risks have not been adequately evaluated; however, owing to similar mechanisms of action, FDA considers upadacitinib may have similar risks A higher rate of all-cause mortality, including sudden cardiovascular death, was observed in patients treated with the JAK inhibitor compared with TNF blockers; consider benefits and risks for individual patient before initiating or continuing treatment, especially the following patients: Who are current or past smokers Who have other cardiovascular risk factors Who have developed a malignancy Who have a known malignancy other than a successfully treated nonmelanoma skin cancer Reserve JAK inhibitors (eg, tofacitinib) if patients have an inadequate response or intolerance to ≥1 TNF blockers Counsel patients about the benefits and risks of these medicines and advise them to seek emergency medical attention if they experience signs and symptoms of a heart attack, stroke, or blood clot Medication residue in stool Reports of medication residue in stool or ostomy output reported; most reports described anatomic (eg, ileostomy, colostomy, intestinal resection) or functional gastrointestinal conditions with shortened gastrointestinal transit times Instruct patients to contact their healthcare provider if medication residue observed repeatedly Monitor patients clinically and consider alternative treatment if there is inadequate therapeutic response Drug interaction overview Substrate of CYP3A4 (major) and CYP2D6 (minor) Strong CYP3A4 inhibitors Use caution; maintain upadacitinib dose to 15 mg qDay Coadministration of upadacitinib 30 mg qDay with strong CYP3A4 inhibitors is not recommended Upadacitinib systemic exposure is increased when coadministered with strong CYP3A4 inhibitors Strong CYP3A4 inducers Coadministration not recommended Upadacitinib systemic exposure is decreased when coadministered with strong CYP3A4 inducers Vaccines Avoid use of live, attenuated, vaccines during or immediately prior to therapy initiation Prior to initiating therapy, it is recommended that patients be brought up to date with all immunizations, including varicella zoster or prophylactic herpes zoster vaccinations, in agreement with current immunization guidelines Ensure vaccinations are current before initiating upadacitinib Pregnancy Available data from the pharmacovigilance safety database and postmarketing case reports in pregnant women are not sufficient to evaluate a drug-associated risk for major birth defects or miscarriage; advise patients of reproductive potential and pregnant patients of potential risk to fetus Verify pregnancy status of females of reproductive potential before starting treatment Report pregnancies to the AbbVie Inc.’s Adverse Event reporting line at 1-888-633-9110, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch Animal data In animal embryo-fetal development studies, oral administration to pregnant rats and rabbits at exposures equal to or greater than approximately 1.6 and 15 times the 15 mg dose, 0.8 and 7.6 times the 30 mg dose, and 0.6 and 5.6 times the maximum recommended human dose (MRHD) of 45 mg (on an AUC basis) resulted in dose-related increases in skeletal malformations (rats only), an increased incidence of cardiovascular malformations (rabbits only), increased post-implantation loss (rabbits only), and decreased fetal body weights in both rats and rabbits No developmental toxicity was observed in pregnant rats and rabbits treated during organogenesis at exposures approximately 0.29 and 2.2 times the 15 mg dose, 0.15 times and 1.1 times the 30 mg dose, and at 0.11 and 0.82 times the MHRD (on an AUC basis) In a pre- and post-natal development study in pregnant female rats, oral administration at exposures approximately 3 times the 15 mg dose, 1.4 times the 30 mg dose, and the same as the MRHD (on an AUC basis) resulted in no maternal or developmental toxicity 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 or ulcerative colitis 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 dosePregnancy Categories A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk. B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done. D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk. X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist. NA: Information not available. Mechanism of Action Janus kinase-1 (JAK1)-selective inhibitor; JAK1 is essential for certain cytokines to elicit signals from various interleukins, cardiotrophin, neurotrophin, and interferons These signals are crucial in maintaining the inflammatory condition in rheumatoid arthritis (RA); inhibition of JAK reduces production of and modulates proinflammatory cytokines central to RA Absorption Peak plasma time: 2-4 hr Steady-state reached within 4 days Distribution Protein bound: 52% Metabolism Metabolized by mainly CYP3A4 and potentially minor contribution from CYP2D6 Elimination Half-life: 8-14 hr Excretion Urine (24%); feces (38%) ~34% of upadacitinib dose was metabolites Oral Administration Take orally with or without food Swallow tablet whole; do not split, crush, or chew Storage Store at 2-25ºC (36-77ºF) Store in original bottle to protect from moisture No images available for this drug. No images available for this drug.A Patient Handout is not currently available for this monograph.Print FormularyPatient DiscountsAdding plans allows you to compare formulary status to other drugs in the same class.To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.Create Your List of PlansAdding plans allows you to:View the formulary and any restrictions for each plan.Manage and view all your plans together – even plans in different states.Compare formulary status to other drugs in the same class.Access your plan list on any device – mobile or desktop. The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information. View explanations for tiers and restrictions Tier Description 1 This drug is available at the lowest co-pay. 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