Genetic Implications:
Pronunciation:
toe-fa-sye-ti-nib
Trade Name(s)
Ther. Class.
Pharm. Class.
kinase inhibitors
Acts as a Janus kinase inhibitor. Some results of inhibition include decreased hematopoiesis and immune cell function. Decreases circulating killer cells, increases B cell count, and decreases serum C-reactive protein.
Therapeutic Effect(s):
Improvement in clinical and symptomatic parameters of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, and polyarticular course juvenile idiopathic arthritis.
Absorption: 74% absorbed following oral administration.
Distribution: Well distributed to tissues.
Metabolism and Excretion: Primarily metabolized by the liver via the CYP3A4 isoenzyme, with some contribution from the CYP2C19 isoenzyme. 30% renal excretion of the parent drug.
Half-life: 3 hr.
TIME/ACTION PROFILE (clinical improvement)
ROUTE | ONSET | PEAK | DURATION |
---|---|---|---|
PO | within 2 wk | 3 mo | unknown |
PO-ER | unknown | unknown | unknown |
Contraindicated in:
Use Cautiously in:
CV: ARTERIAL THROMBOSIS, CARDIOVASCULAR DEATH, DEEP VEIN THROMBOSIS, MI, peripheral edema
Derm: erythema, pruritus, rash
F and E: dehydration
GI: ↑ liver enzymes, abdominal pain, diarrhea, dyspepsia, gastritis, GI PERFORATION, vomiting
GU: ↑ serum creatinine
Hemat: anemia, neutropenia
Metabolic: hyperlipidemia
MS: arthralgia, joint swelling, musculoskeletal pain, tendonitis
Neuro: fatigue, headache, insomnia, paresthesia, STROKE
Resp: PULMONARY EMBOLISM
Misc: DEATH, fever, HYPERSENSITIVITY REACTIONS (including angioedema and urticaria), INFECTION (including tuberculosis [TB], bacterial, invasive fungal infections, viral, and other infections due to opportunistic pathogens), MALIGNANCY
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
Drug-Drug
Rheumatoid Arthritis, Psoriatic Arthritis, and Ankylosing Spondylitis
PO (Adults): Immediate-release tablets: 5 mg twice daily; Extended-release tablets: 11 mg once daily; Concurrent use of strong CYP3A4 inhibitors or concurrent use of moderate CYP3A4 inhibitor with a strong CYP2C19 inhibitor: 5 mg once daily (immediate-release tablets); if taking 11 mg once daily (extended-release tablets), then switch to 5 mg once daily (immediate-release tablets).
Renal Impairment
PO (Adults): Moderate or severe renal impairment: 5 mg once daily (immediate-release); if taking 11 mg once daily (extended-release tablets), then switch to 5 mg once daily (immediate-release tablets). For patients undergoing hemodialysis, administer dose after dialysis session.
Hepatic Impairment
PO (Adults): Moderate hepatic impairment: 5 mg once daily (immediate-release tablets); if taking 11 mg once daily (extended-release tablets), then switch to 5 mg once daily (immediate-release tablets).
Ulcerative Colitis
PO (Adults): Immediate-release tablets: Induction: 10 mg twice daily for ≥8 wk; based on therapeutic response, may transition to maintenance dose or continue 10 mg twice daily for an additional 8 wk. Discontinue therapy if inadequate response achieved after 16 wk using 10 mg twice daily. Maintenance: 5 mg twice daily; if patient experiences loss of response on 5 mg twice daily, then use 10 mg twice daily after assessing the benefits and risks and use for the shortest duration; use lowest effective dose to maintain response; Extended-release tablets: Induction: 22 mg once daily for ≥8 wk; based on therapeutic response, may transition to maintenance dose or continue 22 mg once daily for an additional 8 wk. Discontinue therapy if inadequate response achieved after 16 wk using 22 mg once daily. Maintenance: 11 mg once daily; if patient experiences loss of response on 11 mg once daily, then use 22 mg once daily after assessing the benefits and risks and use for the shortest duration; use lowest effective dose to maintain response; Concurrent use of strong CYP3A4 inhibitors or concurrent use of moderate CYP3A4 inhibitor with a strong CYP2C19 inhibitor: if taking 10 mg twice daily (immediate-release tablets), ↓ to 5 mg twice daily (immediate-release tablets); if taking 5 mg twice daily (immediate-release tablets), ↓ to 5 mg once daily (immediate-release tablets). If taking 22 mg once daily (extended-release tablets), then ↓ to 11 mg once daily (extended-release tablets); if taking 11 mg once daily (extended-release tablets), then switch to 5 mg once daily (immediate-release tablets).
Renal Impairment
PO (Adults): Moderate or severe renal impairment: if taking 10 mg twice daily (immediate-release tablets), ↓ to 5 mg twice daily (immediate-release tablets); if taking 5 mg twice daily (immediate-release tablets), ↓ to 5 mg once daily (immediate-release tablets). If taking 22 mg once daily (extended-release tablets), then ↓ to 11 mg once daily (extended-release tablets); if taking 11 mg once daily (extended-release tablets), then switch to 5 mg once daily (immediate-release tablets). For patients undergoing hemodialysis, administer dose after dialysis session.
Hepatic Impairment
PO (Adults): Moderate hepatic impairment: if taking 10 mg twice daily (immediate-release tablets), ↓ to 5 mg twice daily (immediate-release tablets); if taking 5 mg twice daily (immediate-release tablets), ↓ to 5 mg once daily (immediate-release tablets). If taking 22 mg once daily (extended-release tablets), then ↓ to 11 mg once daily (extended-release tablets); if taking 11 mg once daily (extended-release tablets), then switch to 5 mg once daily (immediate-release).
Active Polyarticular Course Juvenile Idiopathic Arthritis
PO (Children ≥ 2 yr and ≥40 kg): Immediate-release tablets or oral solution: 5 mg twice daily. Concurrent use of strong CYP3A4 inhibitors or concurrent use of moderate CYP3A4 inhibitor with a strong CYP2C19 inhibitor: 5 mg once daily (immediate-release tablets or oral solution).
PO (Children ≥ 2 yr and 20–<40 kg): Oral solution: 4 mg twice daily. Concurrent use of strong CYP3A4 inhibitors or concurrent use of moderate CYP3A4 inhibitor with a strong CYP2C19 inhibitor: 4 mg once daily (oral solution).
PO (Children ≥ 2 yr and 10–<20 kg): Oral solution: 3.2 mg twice daily. Concurrent use of strong CYP3A4 inhibitors or concurrent use of moderate CYP3A4 inhibitor with a strong CYP2C19 inhibitor: 3.2 mg once daily (oral solution).
Renal Impairment
PO (Children ≥ 2 yr): Moderate or severe renal impairment: ≥40 kg: 5 mg once daily (immediate-release tablets or oral solution); 20–<40 kg: 4 mg once daily (oral solution). 10–<20 kg: 3.2 mg once daily (oral solution). For patients undergoing hemodialysis, administer dose after dialysis session.
Hepatic Impairment
PO (Children ≥2 yr): Moderate hepatic impairment: ≥40 kg: 5 mg once daily (immediate-release tablets or oral solution); 20–<40 kg: 4 mg once daily (oral solution). 10–<20 kg: 3.2 mg once daily (oral solution).
Immediate-release tablets: 5 mg, 10 mg
Extended-release tablets: 11 mg, 22 mg
Oral solution (grape flavor): 1 mg/mL
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, prior to and periodically during therapy. Interrupt therapy if patient develops an active infection. Monitor new infections closely; most common are pneumonia, cellulitis, herpes zoster, urinary tract infection, diverticulitis, and appendicitis. Infections may be fatal, especially in patients taking immunosuppressive therapy.
Assess for signs and symptoms of systemic fungal infections (fever, malaise, weight loss, sweats, cough, dypsnea, pulmonary infiltrates, serious systemic illness with or without concomitant shock). Ascertain if patient lives in or has traveled to areas of endemic mycoses. Consider empiric antifungal treatment for patients at risk of histoplasmosis and other invasive fungal infections until the pathogens are identified. Consult with an infectious diseases specialist. Consider stopping tofacitinib until the infection has been diagnosed and adequately treated.
Lab Test Considerations:
Monitor CBC prior to and periodically during therapy. Do not initiate tofacitinib in patients with lymphocyte count <500 cells/mm3 , an ANC <1000 cells/mm3 , or who have Hgb <9 g/dL.
Administer a tuberculin skin test prior to administration of tofacitinib. Patients with active latent TB should be treated for TB prior to 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) or stomach or intestinal perforation (fever, stomach-area pain that does not go away, change in bowel habits) occur.