upadacitinib

REMS

Rinvoq

Treatment of the following disorders:
- Moderately to severely active rheumatoid arthritis in patients who have had an inadequate response/intolerance to ≥1 tumor necrosis factor (TNF) blocker (not to be used with other Janus kinase [JAK] inhibitors, biologic disease-modifying antirheumatic drugs [DMARDs] or potent immunosuppressants [including azathioprine or cyclosporine]);
- Refractory, moderate to severe atopic dermatitis in patients whose disease is not adequately controlled with other systemic drug products, including biologics, or when use of those therapies are not recommended (not to be used with other JAK inhibitors, biologic immunomodulators, or other immunosuppressants);
- Moderately to severely active ulcerative colitis in patients who have had an inadequate response/intolerance to ≥1 TNF blocker (not to be used with other JAK inhibitors, biological therapies, or potent immunosuppressants [including azathioprine or cyclosporine]);
- Moderately to severely active Crohn's disease in patients who have had an inadequate response/intolerance to ≥1 TNF blocker (not to be used with other JAK inhibitors, biological therapies, or potent immunosuppressants [including azathioprine or cyclosporine]);
- Active ankylosing spondylitis in patients who have had an inadequate response/intolerance to ≥1 TNF blocker (not to be used with other JAK inhibitors, biologic DMARDs, or potent immunosuppressants [including azathioprine or cyclosporine]);
- Active non-radiographic axial spondyloarthritis in patients with objective signs of inflammation who have had an inadequate response or intolerance to TNF blocker therapy (not to be used with other JAK inhibitors, biologic DMARDs, or potent immunosuppressants [including azathioprine or cyclosporine]).

Rinvoq and Rinvoq LQ

Treatment of the following disorders:
- Active psoriatic arthritis in patients who have had an inadequate response/intolerance to ≥1 TNF blocker (not to be used with other JAK inhibitors, biologic DMARDs or potent immunosuppressants [including azathioprine or cyclosporine]);
- Active polyarticular juvenile idiopathic arthritis in patients who have had an inadequate response or intolerance to ≥1 TNF blocker (not to be used with other JAK inhibitors, biologic DMARDs, or potent immunosuppressants [including azathioprine or cyclosporine]).

Action ⬆ ⬇

Inhibits JAK enzymes, which prevents the activation of signal transducers, and activators of transcription, which ultimately results in decreased hematopoiesis and immune cell function.

Therapeutic effects:

Improvement in clinical and symptomatic parameters of rheumatoid arthritis, psoriatic arthritis, atopic dermatitis, ulcerative colitis, Crohn's disease, ankylosing spondylitis, and non-radiographic axial spondyloarthritis.

Pharmacokinetics ⬆ ⬇

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

Metabolism/Excretion: Primarily metabolized by the liver via the CYP3A4 isoenzyme and to a lesser extent by the CYP2D6 isoenzyme; 38% excreted in feces and 24% excreted in urine as unchanged drug.

Half-Life: 8–14 hr.

Time/Action Profile ⬆ ⬇

(clinical improvement)

ROUTE	ONSET	PEAK	DURATION
PO	within 2 wk	3 mo	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Active infection;
Lymphocyte count <500 cells/mm³, ANC <1000 cells/mm³, or Hgb <8 g/dL;
↑risk for thrombosis;
History of MI or stroke;
Severe hepatic impairment;
End-stage renal disease (CCr <15 mL/min) (atopic dermatitis and ulcerative colitis only);
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Patients who are >50 yr old and have ≥1 cardiovascular risk factor (↑ risk of all-cause mortality, cardiovascular death, MI, stroke, and thrombosis);
Current or past history of smoking (↑ risk of malignancy, cardiovascular death, MI, or stroke);
Known malignancy;
Previously exposed to tuberculosis (TB);
History of serious or opportunistic infection;
Resided or traveled in areas of endemic TB or endemic mycoses;
Underlying conditions that predispose to infection;
History of diverticulitis or use of NSAIDs (↑ risk of GI perforation);
End-stage renal disease;
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children <18 yr (rheumatoid arthritis and ulcerative colitis), <12 yr (atopic dermatitis), or <2 yr (psoriatic arthritis and polyarticular juvenile idiopathic arthritis).

Adv. Reactions/Side Effects ⬆ ⬇

CV: ARTERIAL THROMBOSIS, CARDIOVASCULAR DEATH, DEEP VEIN THROMBOSIS, MI

GI: ↑liver enzymes, GI PERFORATION, nausea

Hemat: anemia, lymphopenia, NEUTROPENIA

Metab: dyslipidemia

MS: ↑CK

Neuro: STROKE

Resp: cough, PULMONARY EMBOLISM

Misc: DEATH, fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS AND ANGIOEDEMA), INFECTION (INCLUDING TB, BACTERIAL, INVASIVE FUNGAL, VIRAL, OR OPPORTUNISTIC INFECTIONS), MALIGNANCY

Interactions ⬆ ⬇

Drug-drug:

May ↑ risk of adverse reactions and ↓ antibody response to live vaccines; avoid concurrent use.
Strong CYP3A4 inhibitors, including ketoconazole or clarithromycin, may ↑ levels and risk of toxicity; avoid concurrent use.
Strong CYP3A4 inducers, including rifampin, may ↓ levels and effectiveness; concurrent use not recommended.
NSAIDs may ↑ risk of GI perforation; concurrent use requires careful monitoring.
↑risk of immunosuppression when used concurrently with other potent immunosuppressants, including azathioprine, cyclosporine, tacrolimus, antineoplastics, or radiation therapy.

Drug-Food:

Grapefruit or grapefruit juice may ↑ levels and risk of toxicity; avoid concurrent use.

Route/Dosage ⬆ ⬇

Rinvoq extended-release tablets are not interchangeable with Rinvoq LQ oral solution.

Rheumatoid Arthritis, Ankylosing Spondylitis, or Non-Radiographic Axial Spondyloarthritis

PO (Adults ): Rinvoq: 15 mg once daily.

Psoriatic Arthritis

PO (Adults ): Rinvoq: 15 mg once daily.
PO (Children ≥2 yr and ≥30 kg): Rinvoq: 15 mg once daily or Rinvoq LQ: 6 mg twice daily.
PO (Children ≥2 yr and 20–<30 kg): Rinvoq LQ: 4 mg twice daily.
PO (Children ≥2 yr and 10–<20 kg): Rinvoq LQ: 3 mg twice daily.

Atopic Dermatitis

PO Geriatric Patients ≥65 yr): Rinvoq: 15 mg once daily.
PO (Adults and Children 12–64 and ≥40 kg): Rinvoq: 15 mg once daily. If adequate response not achieved, may ↑ to 30 mg once daily. If adequate response not achieved with 30 mg once daily, discontinue therapy. Concurrent use of strong CYP3A4 inhibitors: Rinvoq: 15 mg once daily.

Renal Impairment

(Adults and Children ≥12 yr and ≥40 kg): CCr 15–<30 mL/min: Rinvoq: 15 mg once daily. CCr <15 mL/min: Rinvoq: Not recommended.

Ulcerative Colitis

PO (Adults ): Induction therapy: Rinvoq: 45 mg once daily for 8 wk. Maintenance therapy: Rinvoq: 15 mg once daily; may ↑ to 30 mg once daily if patients have refractory, severe, or extensive disease. If adequate response not achieved with 30 mg once daily, discontinue therapy. Concurrent use of strong CYP3A4 inhibitors: Induction therapy (Rinvoq): 30 mg once daily for 8 wk. Maintenance therapy (Rinvoq): 15 mg once daily.

Renal Impairment

PO (Adults ): CCr 15–<30 mL/min: Induction therapy (Rinvoq): 30 mg once daily for 8 wk. Maintenance therapy (Rinvoq): 15 mg once daily. CCr <15 mL/min: Rinvoq: Not recommended.

Hepatic Impairment

PO (Adults ): Mild or moderate hepatic impairment: Induction therapy (Rinvoq): 30 mg once daily for 8 wk. Maintenance therapy (Rinvoq): 15 mg once daily.

Crohn's Disease

PO (Adults ): Induction therapy: Rinvoq: 45 mg once daily for 12 wk. Maintenance therapy: Rinvoq: 15 mg once daily; may ↑ to 30 mg once daily if patients have refractory, severe, or extensive disease. If adequate response not achieved with 30 mg once daily, discontinue therapy. Concurrent use of strong CYP3A4 inhibitors: Induction therapy (Rinvoq): 30 mg once daily for 12 wk. Maintenance therapy (Rinvoq): 15 mg once daily.

Renal Impairment

PO (Adults ): CCr 15–<30 mL/min: Induction therapy (Rinvoq): 30 mg once daily for 12 wk. Maintenance therapy (Rinvoq): 15 mg once daily. CCr <15 mL/min:Rinvoq: Not recommended.

Hepatic Impairment

PO (Adults ): Mild or moderate hepatic impairment: Induction therapy (Rinvoq): 30 mg once daily for 12 wk. Maintenance therapy (Rinvoq): 15 mg once daily.

Polyarticular Juvenile Idiopathic Arthritis

PO (Children ≥2 yr and ≥30 kg): Rinvoq: 15 mg once daily or Rinvoq LQ: 6 mg twice daily.
PO (Children ≥2 yr and 20–<30 kg): Rinvoq LQ: 4 mg twice daily.
PO (Children ≥2 yr and 10–<20 kg): Rinvoq LQ: 3 mg twice daily.

Availability ⬆ ⬇

Extended-release tablets (Rinvoq): 15 mg; 30 mg; 45 mg
Oral solution (Rinvoq LQ): 1 mg/mL

Assessment ⬆ ⬇

Assess pain and range of motion before and periodically during therapy.
Assess for signs of infection (fever, dyspnea, flu-like symptoms, frequent or painful urination, redness or swelling at the site of a wound), including TB and hepatitis B virus, prior to and periodically during therapy. Monitor new infections closely; most common are upper respiratory tract infections, bronchitis, and urinary tract infections. Infections may be fatal, especially in patients taking immunosuppressive therapy. If patient develops a serious infection, including serious opportunistic infection, interrupt therapy until infection is controlled.
Assess patient for latent TB with a tuberculin skin test prior to initiation of therapy. Treatment of latent TB should be started before therapy with upadacitinib.
Screen patient for hepatitis B virus infection before starting therapy.
Assess skin for new lesions periodically during therapy; ↑ risk of skin cancer.
Monitor for signs and symptoms of thrombosis (swelling, pain or tenderness in the leg, sudden unexplained chest pain, shortness of breath) during therapy.
Monitor patients at risk for GI perforation (patients with a history of diverticulitis and those taking concomitant medications, including NSAIDs or corticosteroids). Evaluate promptly patients presenting with new-onset abdominal pain for early identification of GI perforation.

Lab Test Considerations:

Verify negative pregnancy test before starting therapy.
- Monitor neutrophil count at baseline and periodically during therapy. Do not start therapy and interrupt therapy if ANC <1000 cells/mm³ and restart therapy once ANC returns above this value.
- Monitor lymphocyte count at baseline and periodically during therapy. Do not start therapy and interrupt therapy if absolute lymphocyte count <500 cells/mm³ and restart therapy once absolute lymphocyte count returns above this value.
- May cause anemia. Monitor Hgb at baseline and periodically during therapy. Do not start therapy and interrupt therapy if Hgb <8 g/dL.
- May ↑ total cholesterol, LDL-C, and HDL-C. Monitor levels 12 wk after starting therapy and periodically thereafter for hyperlipidemia.
- Monitor liver enzymes at baseline and periodically thereafter. If AST or ALT are ↑ and drug-induced liver injury is suspected, hold upadacitinib.

Implementation ⬆ ⬇

Immunizations, including prophylactic zoster vaccinations, should be current before starting therapy. Patients on upadacitinib may receive concurrent vaccinations, except for live vaccines.
PO: Extended-release tablets: Administer once daily without regard to food. DNC: Swallow tablets whole; do not split, crush, or chew. Oral solution: Administer twice daily without regard to food using the provided press-in bottle adapter and oral dosing syringe.

Patient/Family Teaching ⬆ ⬇

Explain the purpose and side effects of upadacitinib to patient. Instruct patient to take upadacitinib as directed. Do not stop receiving drug without consulting health care professional. Advise patient to read Patient Information before starting therapy and with each Rx refill in case of changes.
Emphasize the importance of regular lab tests to monitor for adverse drug reactions.
Caution patient to avoid grapefruit or grapefruit juice during therapy.
Advise patient to avoid live vaccines during therapy.
Caution patient to notify health care professional immediately if signs of infection (fever; sweating; chills; muscle aches; cough; shortness of breath; blood in phlegm; weight loss; warm, red, or painful skin or sores; diarrhea or stomach pain; burning on urination or urinating more often than normal; feeling very tired), blood clots, or stomach or intestinal perforation (fever, stomach-area pain that does not go away, change in bowel habits) occur.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
Instruct patient to notify health care professional of medication regimen prior to treatment or surgery.
Inform patient of ↑ risk of lymphoma and other cancers. Advise patient to have periodic skin exams for new lesions of skin cancer.
Inform patient of ↑ risk of cardiovascular events. Warn patient to report symptoms of heart attack (chest pain, trouble breathing, sweating, dizziness, nausea) and stroke (weakness, slurred speech, confusion, dizziness).
Instruct patients to contact their health care professional if medication residue is observed repeatedly in stool or ostomy output.
Rep: May cause fetal harm. Advise women of reproductive potential to use effective contraception during and for 4 wk after final dose and to avoid breastfeeding during therapy and for 6 days after last dose. Advise patient to notify health care professional immediately if pregnancy is planned or suspected. If pregnancy occurs during therapy, report to the AbbVie Inc.’s Adverse Event reporting line at 1-800-633-9110, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆ ⬇

Code ⬆