Imbruvica

Ibrutinib

As a single agent for the treatment of adult patients w/ relapsed or refractory mantle cell lymphoma. As a single agent or in combination w/ rituximab or obinutuzumab for the treatment of adult patients w/ previously untreated chronic lymphocytic leukaemia (CLL). As a single agent or in combination w/ bendamustine & rituximab (BR) for treatment of adults w/ CLL who have received at least 1 prior therapy. As a single agent for the treatment of adults w/ Waldenström's macroglobulinaemia (WM) who have received at least 1 prior therapy, or in 1st line treatment for patients unsuitable for chemo-immunotherapy. In combination w/ rituximab for treatment of adults w/ WM.

Mantle cell lymphoma 560 mg once daily. Chronic lymphocytic leukaemia 420 mg once daily, either as a single agent or in combination. Waldenström's macroglobulinaemia 420 mg once daily, either as a single agent or in combination. Recommended to administer Imbruvica prior to anti-CD20 therapy when given on the same day. Patient w/ mild liver impairment (Child-Pugh class A) 280 mg daily; moderate liver impairment (Child-Pugh class B) 140 mg daily.

Should be taken with food: Take at the same time each day. Swallow whole w/ water. Do not break/chew. Do not take w/ grapefruit juice or Seville oranges.

Hypersensitivity. Concomitant use w/ St. John's wort-containing prep.

Reports of bleeding events w/ or w/o thrombocytopenia; leukostasis; splenic rupture following treatment discontinuation; infections (including sepsis, neutropenic sepsis, bacterial, viral, or fungal infections); cytopenias; interstitial lung disease (ILD); cardiac arrhythmia & cardiac failure; cerebrovascular accidents; tumour lysis syndrome; non-melanoma skin cancer; hepatitis B reactivation; HTN; haemophagocytic lymphohistiocytosis. Should not be concomitantly administered w/ warfarin or other vit K antagonists. Avoid supplements eg, fish oil & vit E prep. Withhold Imbruvica at least 3-7 days pre- & post-surgery depending upon the type of surgery & the risk of bleeding. Consider temporarily withholding treatment in case of leukostasis; closely monitor patients & administer supportive care including hydration &/or cytoreduction as indicated. Monitor disease status & spleen size when treatment is interrupted or ceased. Monitor patients for fever, neutropenia & infections, & institute appropriate anti-infective therapy as indicated. Consider prophylaxis according to standard of care in patients who are at increased risk for opportunistic infections. Consider progressive multifocal leukoencephalopathy (PML) in the differential diagnosis in patients w/ new or worsening neurological, cognitive, or behavioral signs or symptoms; perform appropriate diagnostic evaluation & suspend treatment until PML is excluded. Monitor complete blood counts mthly. Monitor patients for pulmonary symptoms indicative of ILD. Interrupt treatment & manage ILD if symptoms develop. Periodically monitor all patients clinically for cardiac manifestations, including cardiac arrhythmia & cardiac failure. Establish HBV status prior to treatment initiation. Monitor & manage patients following local medical standards to prevent hepatitis B reactivation. Regularly monitor BP & initiate or adjust antihypertensive medication as appropriate. Closely monitor patients for signs of Imbruvica toxicity if a CYP3A4 inhibitor must be used. Closely monitor patients for signs of Imbruvica lack of efficacy if a CYP3A4 inducer must be used. Patients w/ hepatic impairment or severe renal impairment. Minor influence on the ability to drive & use machines. Women of childbearing potential must use a highly effective method of contraception while on treatment & for 3 mth after stopping treatment. Should not be used during pregnancy. Discontinue breast-feeding during treatment. Paed population. Patients w/ severe CV disease.

Diarrhoea, neutropenia, musculoskeletal pain, rash, haemorrhage, thrombocytopenia, nausea, pyrexia, arthralgia, upper resp tract infection.

Increased plasma conc w/ strong CYP3A4 inhibitors (eg, ketoconazole, indinavir, nelfinavir, ritonavir, saquinavir, clarithromycin, telithromycin, itraconazole, nefazodone, cobicistat, voriconazole & posaconazole) or moderate CYP3A4 inhibitors (eg, fluconazole, erythromycin, amprenavir, aprepitant, atazanavir, ciprofloxacin, crizotinib, diltiazem, fosamprenavir, imatinib, verapamil, amiodarone & dronedarone); grapefruit & Seville oranges. Decreased plasma conc w/ strong or moderate CYP3A4 inducers (eg, carbamazepine, rifampicin, phenytoin). Reduced efficacy w/ prep containing St. John's Wort. Potential interaction w/ P-gp or BCRP substrates w/ narrow therapeutic range (eg, digoxin, methotrexate); drugs that undergo BCRP-mediated hepatic efflux eg, rosuvastatin.

Targeted Cancer Therapy

L01EL01 - ibrutinib ; Belongs to the class of Bruton's tyrosine kinase (BTK) inhibitors. Used in the treatment of cancer.

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