upadacitinib

General

Pronunciation:
ue-pad-a-sye-ti-nib


Trade Name(s)

  • Rinvoq

Ther. Class.

antirheumatics

Pharm. Class.

kinase inhibitors

Indications

Moderately to severely active rheumatoid arthritis (RA) in patients who have had an inadequate response/intolerance to methotrexate (as monotherapy or in combination with methotrexate) (not to be used with other Janus kinase [JAK] inhibitors, biologic disease-modifying antirheumatic drugs [DMARDs] or potent immunosuppressants [including azathioprine or cyclosporine]).

Action

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

Therapeutic Effect(s):

Improvement in clinical and symptomatic parameters of RA.

Pharmacokinetics

Absorption: Well absorbed following oral administration.

Distribution: Distributes equally between red blood cells and plasma.

Metabolism and Excretion: Primarily metabolized by the liver via the CYP3A4 isoenzyme (with some contribution from CYP2D6); 38% excreted in feces and 24% excreted in urine as unchanged drug.

Half-life: 8–14 hr.

TIME/ACTION PROFILE (clinical improvement)

ROUTEONSETPEAKDURATION
POwithin 2 wk3 mounknown

Contraindication/Precautions

Contraindicated in:

  • Active infection;
  • Lymphocyte count <500 cells/mm3 , absolute neutrophil count (ANC) <1000 cells/mm3 , or hemoglobin levels <8 g/dL;
  • Severe hepatic impairment;
  • OB:   Pregnancy (may cause fetal harm)
  • Lactation: Lactation.

Use Cautiously in:

  • Previously exposed to tuberculosis
  • History of serious or opportunistic infection
  • Resided or traveled in areas of endemic tuberculosis or endemic mycoses
  • Underlying conditions that predispose to infection
  • Malignancy (other than successfully treated non-melanoma skin cancer)
  • ↑ risk for thrombosis
  • History of diverticulitis or use of nonsteroidal anti-inflammatory drugs (NSAIDs) (↑ risk of GI perforation);
  • End-stage renal disease
  • Rep:   Women of reproductive potential
  • Pedi:  Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

CV: ARTERIAL THROMBOSIS, DEEP VEIN THROMBOSIS

GI: GI PERFORATION, ↑ liver enzymes, nausea

Hemat: NEUTROPENIA, anemia, lymphopenia

Metabolic: dyslipidemia

MS: ↑ creatine kinase

Resp: PULMONARY EMBOLISM, cough

Misc: INFECTION (including tuberculosis, bacterial, invasive fungal, viral, or opportunistic infections; tuberculosis; and reactivation of herpes virus or hepatitis B virus), MALIGNANCY, fever

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

  • May ↑ risk of adverse reactions and ↓ antibody response to  live vaccines ; avoid concurrent use.
  •  Strong CYP3A4 inhibitors, including  ketoconazole , may ↑ levels and risk of toxicity; use concurrently with caution.
  •  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.

Route/Dosage

PO (Adults): 15 mg once daily.

Availability

Extended-release tablets: 15 mg

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 tuberculosis and Hepatitis B virus (HBV), prior to and periodically during therapy. Upadacitinib is contraindicated in patients with active infection. 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.
  • Assess patient for latent tuberculosis with a tuberculin skin test prior to initiation of therapy. Treatment of latent tuberculosis should be started before therapy with upadacitinib.
  • Assess skin for new lesions periodically during therapy; risk of skin cancer is increased.
  • Monitor for signs and symptoms of thrombosis (swelling, pain or tenderness in the leg, sudden unexplained chest pain, shortness of breath) during therapy.

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 (ALC) <500 cells/mm3  and restart therapy once ALC returns above this value.
  • May cause anemia. Monitor hemoglobin at baseline and periodically during therapy. Do not start therapy and interrupt therapy if hemoglobin level <8 g/dL.
  • May cause increases in total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol. 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 increased and drug-induced liver injury is suspected, hold upadacitinib.

Implementation

  • Immunizations, prophylactic zoster vaccinations, should be current before starting therapy. Patients on upadacitinib may receive concurrent vaccinations, except for live vaccines.

  • Administer a tuberculin skin test prior to administration of upadacitinib. Patients with active latent TB should be treated for TB prior to therapy.

    • Screen patient for viral hepatitis before starting therapy.
  • PO Administer once daily without regard to food.  DNC: Swallow tablets whole; do not split, crush, or chew. 

Patient/Family Teaching

  • Instruct patient to take upadacitinib as directed. Advise patient to read  Patient Information  before starting therapy and with each Rx refill in case of changes.
  • 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 increased risk of lymphoma and other cancers. Advise patient to have periodic skin exams for new lesions of skin cancer.
  • Rep:   May cause fetal harm. Advise females of reproductive potential to use effective contraception during and for 4 wk after final dose and to avoid breastfeeding during and for 6 days (10 half-lives) after last dose. Advise patient to notify health care professional immediately if pregnancy is suspected.
  • Emphasize the importance of regular lab tests to monitor for adverse drug reactions.

Evaluation/Desired Outcomes

Improved physical function and decreased fatigue.