Imbruvica

Mantle cell lymphoma (MCL) in adults. Monotherapy or in combination w/ rituximab, obinutuzumab or venetoclax for adults w/ previously untreated chronic lymphocytic leukaemia (CLL). Monotherapy or in combination w/ bendamustine & rituximab for adults w/ CLL who have received at least 1 prior therapy. Monotherapy for 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 WM. Chronic graft-versus-host disease (cGVHD) after failure of ≥1 lines of systemic therapy.

MCL Recommended dose: 560 mg once daily until disease progression or no longer tolerated by patient. CLL & WM Recommended dose: 420 mg once daily. Continue treatment until disease progression or no longer tolerated by patient. CLL In combination w/ venetoclax: Administer as single agent for 3 cycles (28 days), followed by 12 cycles w/ venetoclax. cGVHD Recommended dose: 420 mg once daily until cGVHD progression, recurrence of an underlying malignancy or unacceptable toxicity. Concomitant administration w/ moderate CYP3A4 inhibitors 280 mg once daily. Concomitant administration w/ strong CYP3A4 inhibitors 140 mg once daily or withheld for up to 7 days. Toxicity occurrence Dose modification should be considered. Mild hepatic impairment 280 mg daily. Moderate hepatic impairment 140 mg daily.

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

Bleeding-related events, avoid co-administration w/ warfarin or other vit K antagonists, monitor signs & symptoms of bleeding, avoid supplements eg, fish oil & vit E prep, withhold therapy 3-7 days pre- & post-op. Monitor leukostasis closely, consider temporarily withholding therapy & administer supportive care. Splenic rupture, monitor disease status & spleen size. Infections, patients w/ DM, COPD/asthma &/or lymphophenia. Monitor for fever, abnormal LFT, neutropenia & infections, institute appropriate anti-infective therapy; monitor CBC mthly. Hepatic events, assess liver function & viral hepatitis before treatment, monitor periodically during treatment. Cytopenias, monitor CBC mthly. ILD, monitor for pulmonary symptoms. Cardiac arrhythmia & cardiac failure, patients w/ advanced age, Eastern Cooperative Oncology Group performance status ≥2, or cardiac co-morbidities. Monitor for signs of clinical deterioration of cardiac function. CVA, transient ischaemic attack, ischaemic stroke including fatalities. Closely monitor tumour lysis syndrome. Non-melanoma skin cancer, monitor for appearance. HTN, regularly monitor BP. Haemophagocytic lymphohistiocytosis. Avoid concomitant use w/ strong CYP3A4 inhibitors & moderate or strong CYP3A4 inducers. Not to be taken by patients w/ galactose intolerance, total lactase deficiency or glucose-galactose malabsorption. May affect ability to drive & use machines. Not recommended in severe hepatic impairment (Child-Pugh C). Severe renal impairment (CrCl <30 mL/min) or on dialysis. Women of childbearing potential should use effective contraception during & for 3 mth after treatment. Not to be used during pregnancy & lactation. Elderly ≥65 yr w/ previously untreated MCL. Not recommended in childn & adolescents ≤18 yr.

Pneumonia, URTI, skin infection; neutropenia, thrombocytopenia, lymphocytosis; dizziness, headache; haemorrhage, bruising, HTN; diarrhoea, vomiting, stomatitis, nausea, constipation, dyspepsia; rash; arthralgia, muscle spasms, musculoskeletal pain; pyrexia, peripheral oedema; increased blood creatinine. Sepsis, UTI, sinusitis; non-melanoma skin cancer, basal & squamous cell carcinoma; febrile neutropenia, leukocytosis; ILD; hyperuricaemia; peripheral neuropathy; blurred vision; cardiac failure, atrial fibrillation; epistaxis, petechiae; urticaria, erythema, onychoclasis; acute kidney injury.

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

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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