deuruxolitinib

Absorption: 90% absorbed following oral administration.

Distribution: Well distributed to tissues.

Metabolism/Excretion: Primarily metabolized in the liver via the CYP2C9 and CYP3A4 isoenzymes and to a lesser extent by the CYP1A2 isoenzyme. The CYP2C9 isoenzyme exhibits genetic polymorphism; poor metabolizers (PMs) may have significantly ↑ deuruxolitinib concentrations and an ↑ risk of adverse effects.

Half-Life: 4 hr.

Time/Action Profile ⬆ ⬇

(plasma concentrations)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1.5 hr	12 hr

Contraind./Precautions ⬆ ⬇

Contraindicated in:

CYP2C9 PMs;
Concurrent use of strong or moderate CYP2C9 inhibitors;
Active, serious infection
;
↑risk of thrombosis;
History of MI or stroke
;
Hgb <8 g/dL;
ANC <1000 cells/mm³;
Lymphocytes <500 cells/mm³;
Severe renal impairment or end-stage renal disease;
Severe hepatic impairment;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

Chronic or recurrent infection
;
Exposed to tuberculosis (TB)
;
History of serious or opportunistic infection
;
Resided or traveled in areas of endemic TB or endemic mycoses
;
Predisposition to infection
;
>50 yr old and with ≥1 cardiovascular risk factor (may have ↑ risk of mortality, cardiovascular death, nonfatal MI, or nonfatal stroke)
;
Current or past history of smoking (↑ risk of malignancy, cardiovascular death, MI, or stroke)
;
Known malignancy
;
History of diverticulitis (↑ risk of GI perforation);
Rep: Women of reproductive potential;
Pedi: Safety and effectiveness not established in children.

Adv. Reactions/Side Effects ⬆ ⬇

CV: ARTERIAL THROMBOSIS, CARDIOVASCULAR DEATH, DEEP VEIN THROMBOSIS (DVT), MI

Derm: acne

EENT: nasopharyngitis

GI: GI PERFORATION

Hemat: anemia, lymphopenia, neutropenia, thrombocytosis

Metab: hyperlipidemia, hypertriglyceridemia, weight gain

MS: ↑CK

Neuro: headache, fatigue, STROKE

Resp: PULMONARY EMBOLISM (PE)

Misc: DEATH, INFECTION(INCLUDING REACTIVATION TB AND OTHER OPPORTUNISTIC INFECTIONS DUE TO BACTERIAL, FUNGAL, VIRAL, AND MYCOBACTERIAL PATHOGENS), MALIGNANCY

Interactions ⬆ ⬇

Drug-drug:

Strong CYP2C9 inhibitors or moderate CYP2C9 inhibitors, including fluconazole, may ↑ levels and risk of toxicity; concurrent use contraindicated.
Strong CYP3A4 inducers, including rifampin, may ↓ levels and effectiveness; avoid concurrent use.
Strong CYP2C9 inducers or moderate CYP2C9 inducers, including rifampin, may ↓ levels and effectiveness; avoid concurrent use.
↑risk of immunosuppression when used concurrently with other potent immunosuppressants, including azathioprine, cyclosporine, tacrolimus, antineoplastics, or radiation therapy.

Route/Dosage ⬆ ⬇

PO (Adults ): 8 mg twice daily.

Availability ⬆ ⬇

Assessment ⬆ ⬇

Assess for signs and symptoms of infection, including opportunistic infections and TB, prior to and periodically during therapy. If sepsis or serious infection occurs, interrupt therapy and provide appropriate diagnostic testing, antimicrobial therapy, and close monitoring. 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, dyspnea, pulmonary infiltrates, serious systemic illness with or without concurrent 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 pathogen identified. Consult with infectious diseases specialist. Consider stopping deuruxolitinib until the infection has been diagnosed and adequately treated.
Monitor for thrombosis, including PE, DVT, and arterial thrombi. If symptoms of thrombosis occur, permanently discontinue deuruxolitinib.

Lab Test Considerations:

Determine CYP2C9 genotype variant prior to initiation. An FDA-approved test is not currently available.
Complete tuberculin skin test prior to initiation of therapy. Treatment of latent TB should be started before therapy with deuruxolitinib.
Screen for viral hepatitis according to guidelines.
Monitor CBC with differential periodically during therapy. If lymphocytes <500 cells/mm³, ANC <1000 cells/mm³, or Hgb <8 g/dL, hold therapy until ≥500 cells/mm³, ≥1000 cells/mm³, or ≥8 g/dL respectively; then resume deuruxolitinib.
Asses lipid panel at baseline and periodically during therapy.
May ↑ CK.

Implementation ⬆ ⬇

Update all age-appropriate vaccines, including herpes zoster, according to guidelines before initiation of therapy.
PO: Administer tablet without regard to food.

Patient/Family Teaching ⬆ ⬇

Explain purpose and side effects of medication. Advise patient to read Patient Information before starting therapy.
- Advise patient if dose is missed to omit and resume at next scheduled dose.
Inform patient of ↑ risk of malignancy, including skin cancer, and that periodic skin exams are recommended.
Advise patient to notify health care provider 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) occur.
Inform patient of ↑ risk of MI, stroke, DVT, PE, and cardiovascular death, especially in current or past smokers, and to notify health care provider if symptoms (chest pain, shortness of breath, nausea, palpitations, fainting, trouble speaking/understanding, unilateral numbness/weakness, visual changes, headache, discoordination; pain/swelling/cramping/pallor of extremity) occur.
Inform patient ≥50 yr of age with ≥1 cardiovascular risk factor that risk of death from all causes is ↑ with deuruxolitinib use. They should discontinue therapy if they experience heart attack or stroke.
Inform patient that risk of malignancy and lymphoproliferative disorders is ↑ with deuruxolitinib use and periodic cancer screens, including skin assessments, are recommended.
Advise patient to notify health care provider promptly for symptoms of GI perforation (stomach pain, fever, chills, nausea, vomiting).
Advise patient not to receive live vaccines during therapy.
Advise patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other medications.
Rep: May cause fetal harm. Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected. Avoid breastfeeding during therapy and for 1 day after last dose. Encourage patient to report pregnancy exposure to Sun Pharmaceutical Industries Inc. at 1-800-818-4555.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇