Pfizer Bortezomib

Bortezomib

Patients w/ multiple myeloma or mantle cell lymphoma who have received at least 1 prior therapy.

IV/SC Monotherapy 1.3 mg/m² twice wkly for 2 wk on days 1, 4, 8 & 11 followed by 10-day rest period (days 12-21) in a 21-day treatment cycle. At least 72 hr should elapse between consecutive doses. Dose adjustment during treatment & re-initiation of treatment for monotherapy Re-initiate at a 25% reduced dose (1.3 mg/m² reduced to 1 mg/m²; 1 mg/m² reduced to 0.7 mg/m²). Combination therapy w/ pegylated lipos doxorubicin 1.3 mg/m² twice wkly for 2 wk on days 1, 4, 8 & 11 in a 21-day treatment cycle. At least 72 hr should elapse between consecutive doses. Administer pegylated lipos doxorubicin at 30 mg/m² on day 4 of the treatment cycle as 1 hr IV infusion. Combination w/ dexamethasone 1.3 mg/m² twice wkly for 2 wk on days 1, 4, 8 & 11 in a 21-day treatment cycle. At least 72 hr should elapse between consecutive doses. Administer oral dexamethasone at 20 mg on days 1, 2, 4, 5, 8, 9, 11 & 12 of the treatment cycle. May continue combination therapy for a max of 4 additional cycles if patient achieves a response or a stable disease after 4 cycles. Combination therapy w/ melphalan & prednisone Cycles 1-4: Administer 1.3 mg/m² twice wkly on days 1, 4, 8, 11, 22, 25, 29 & 32. Cycles 5-9: Administer 1.3 mg/m² once wkly on days 1, 8, 22 & 29. At least 72 hr should elapse between consecutive doses. Administer oral melphalan (9 mg/m²) & prednisone (60 mg/m²) on days 1-4 of the 1st wk of each treatment cycle. Combination therapy w/ dexamethasone & thalidomide 1.3 mg/m² twice wkly for 2 wk on days 1, 4, 8 & 11 in a 28-day treatment cycle. At least 72 hr should elapse between consecutive doses. Administer oral dexamethasone at 40 mg on days 1-4 & 8-11 of the treatment cycle. Administer oral thalidomide at 50 mg on days 1-14 & if tolerated, may increase to 100 mg on days 15-18, thereafter may be further increased to 200 mg daily from cycle 2. 2 additional cycles are recommended in patient w/ at least partial response. Moderate to severe hepatic impairment Initially, reduced dose of 0.7 mg/m² during the 1st treatment cycle, & a subsequent dose escalation to 1 mg/m² or further dose reduction to 0.5 mg/m² may be considered based on patient tolerability.

Hypersensitivity to bortezomib or boron. Acute diffuse infiltrative pulmonary & pericardial disease.

Do not administer intrathecally. Closely monitor patients who experience constipation. Monitor platelet counts prior to each dose; w/held therapy when platelet count is <25,000/uL or, ≤30,000/uL when in combination w/ melphalan & prednisone. Monitor for signs & symptoms of infection in patients w/ neutropenia due to increased risk of infections. Consider prophylactic use of granulocyte colony stimulating factors in case of repeated delays in cycle administration. Herpes zoster reactivation. Antiviral prophylaxis is recommended during treatment. Perform HBV screening before initiation of combination treatment w/ rituximab in patients at risk of infection; closely monitor for clinical & lab sign of active HBV infection during & following rituximab combination treatment in patients who are carriers or w/ history of hepatitis B. Monitor at regular intervals for any new or worsening neurological symptoms or signs suggestive of progressive multifocal leukoencephalopathy (PML) as part the differential diagnosis of CNS problems; discontinue treatment if PML is diagnosed. Neurological evaluation for patients experiencing new or worsening peripheral neuropathy; consider early & regular monitoring for symptoms of treatment-emergent neuropathy in combination w/ medicines associated w/ neuropathy (eg, thalidomide). Patients w/ any risk factors for seizures. Orthostatic/postural hypotension. Discontinue if posterior reversible encephalopathy syndrome develops. Acute development or exacerbation of CHF, &/or new onset of decreased left ventricular ejection fraction. Closely monitor patients w/ risk factors for or existing heart disease. Perform prompt diagnostic evaluation in the event of new or worsening pulmonary symptoms. Complications of tumour lysis syndrome may occur. Discontinue if potentially immunocomplex-mediated reactions eg, serum-sickness-type reaction, polyarthritis w/ rash & proliferative glomerulonephritis occurs. Combination w/ potent CYP3A4 inhibitors & CYP3A4 or CYP2C19 substrates. Patients receiving oral hypoglycaemics. May have moderate influence on the ability to drive & use machines. Renal & hepatic impairment. Effective contraceptive measures during & for 3 mth following treatment in female patients of childbearing potential & male patients. Pregnancy. Discontinue use during lactation. Childn <18 yr.

Nausea, diarrhoea, constipation, vomiting, fatigue, pyrexia, thrombocytopenia, anaemia, neutropenia, peripheral neuropathy (including sensory), headache, paraesthesia, decreased appetite, dyspnoea, rash, herpes, zoster & myalgia.

Increased mean AUC w/ potent CYP3A4 inhibitors (eg, ketoconazole, ritonavir). Reduced efficacy w/ strong CYP3A4 inducers (eg, rifampicin, carbamazepine, phenytoin, phenobarb, & St. John's wort). Hypoglycemia & hyperglycemia w/ oral hypoglycaemics.

Targeted Cancer Therapy

L01XG01 - bortezomib ; Belongs to the class of proteasome inhibitors. Used in the treatment of cancer.

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