Zomod 3.5

Bortezomib

Progressive multiple myeloma in adults who have received at least 1 prior therapy & have undergone or are unsuitable for haematopoietic stem cell transplantation as monotherapy or in combination w/ pegylated liposomal doxorubicin or dexamethasone. Previously untreated multiple myeloma in adults who are not eligible for high-dose chemotherapy w/ haematopoietic stem cell transplantation in combination w/ melphalan & prednisone. Induction treatment of previously untreated multiple myeloma in adults who are eligible for high-dose chemotherapy w/ haematopoietic stem cell transplantation in combination w/ dexamethasone or w/ dexamethasone & thalidomide.

Monotherapy: 1.3 mg/m² IV/SC twice wkly for 2 wk on days 1, 4, 8 & 11 in a 21-day treatment cycle w/ at least 72 hr elapse between consecutive doses. Re-initiate treatment from 1.3 mg/m² reduced to 1 mg/m² to 0.7 mg/m². Neuropathic pain &/or peripheral neuropathy Grade 1 w/ pain or Grade 2: Reduce dose to 1 mg/m² or change treatment schedule to 1.3 mg/m² once wkly. Grade 2 w/ pain or Grade 3: Reduce dose to 0.7 mg/m² once wkly. Combination therapy w/ pegylated liposomal doxorubicin 1.3 mg/m² IV/SC twice wkly for 2 wk on days 1, 4, 8 & 11 in a 21-day treatment cycle + pegylated liposomal doxorubicin at 30 mg/m² on day 4 of treatment cycle as 1-hr IV infusion after bortezomib inj. May administer up to 8 cycles as long as patient have not progressed & tolerate treatment. Combination w/ dexamethasone 1.3 mg/m² twice wkly for 2 wk on days 1, 4, 8 & 11 in a 21-day treatment cycle + dexamethasone 20 mg PO on days 1, 2, 4, 5, 8, 9, 11 & 12. At least 72 hr should elapse between consecutive doses of bortezomib. Dose adjustments for combination therapy for patient w/ progressive multiple myeloma 1.3 mg/m² IV/SC twice wkly for 2 wk on days 1, 4, 8 & 11 in a 21-day treatment cycle w/ at least 72 hr elapse between consecutive doses. Combination therapy w/ melphalan & prednisone Administer 1.3 mg/m² IV/SC for 6 wk. Cycles 1-4: Administer bortezomib twice wkly on days 1, 4, 8, 11, 22, 25, 29 & 32. Cycles 5-9: Administer bortezomib once wkly on days 1, 8, 22 & 29. Melphalan & prednisone should both be given PO on days 1, 2, 3 & 4 of the 1st wk of each treatment cycle. Should be administered in 9 treatment cycles. Induction therapy in previously untreated multiple myeloma patient eligible for haematopoietic stem cell transplantation: Combination therapy w/ dexamethasone 1.3 mg/m² IV/SC twice wkly for 2 wk on days 1, 4, 8, & 11 in a 21-day treatment cycle + dexamethasone 40 mg PO on days 1, 2, 3, 4, 8, 9, 10 & 11 administered in 4 treatment cycles. Combination therapy w/ dexamethasone & thalidomide 1.3 mg/m² IV/SC twice wkly for 2 wk on days 1, 4, 8 & 11 in a 28-day treatment cycle + dexamethasone 40 mg PO on days 1, 2, 3, 4, 8, 9, 10 & 11 & thalidomide 50 mg daily PO on days 1-14, may increase to 100 mg on days 15-28 & to 200 mg daily from cycle 2 if dose is well tolerated. Should be administered in 4 treatment cycles & 2 additional cycles in patients w/ least partial response. Moderate or severe hepatic impairment 0.7 mg/m² per inj during 1st treatment cycle, & subsequent increase to 1 mg/m² or further reduce to 0.5 mg/m² based on patient tolerability.

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

Do not administer intrathecally. Constipation, existing heart disease, high tumour burden prior to treatment. Monitor CBC w/ differential & platelet count prior & during treatment, stop treatment if platelet count is <25,000/μL or ≤30,000/μL in combination w/ melphalan & prednisone. HZV reactivation. Discontinue treatment if progressive multifocal leukoencephalopathy & posterior reversible encephalopathy syndrome is diagnosed. Peripheral neuropathy, seizures. Patients w/ history of syncope receiving medicinal products known to be associated w/ hypotension. ECG investigations, pulmonary disorders. Not recommended w/ high-dose cytarabine (2 g/m²/day) by continuous infusion over 24 hr. Hepatic & potentially immunocomplex-mediated reactions. Concomitant use w/ potent CYP3A4-inhibitors & CYP3A4 or CYP2C19 substrates. May moderately influence the ability to drive & use machines. Renal & hepatic impairment. Men & women of childbearing potential. Pregnancy. Discontinue lactation during treatment. Childn <18 yr.

Thrombocytopenia, neutropenia, anaemia; decreased appetite; neuropathies, peripheral sensory neuropathy, dysaesthesia, neuralgia; nausea & vomiting symptoms, diarrhoea, constipation; musculoskeletal pain; pyrexia, fatigue, asthenia. Herpes zoster (including disseminated & ophth), pneumonia, herpes simplex, fungal infection; leukopenia, lymphopenia; dehydration, hypokalaemia, hyponatraemia, abnormal blood glucose, hypocalcaemia, enzyme abnormality; mood disorders & disturbances, anxiety disorder, sleep disorders & disturbances; motor neuropathy, loss of consciousness (including syncope), dizziness, dysgeusia, lethargy, headache; eye swelling, abnormal vision, conjunctivitis; vertigo; hypotension, orthostatic hypotension, HTN; dyspnoea, epistaxis, upper/lower resp tract infection, cough; GI haemorrhage (including mucosal), dyspepsia, stomatitis, abdominal distention, oropharyngeal pain, abdominal pain (including GI & splenic pain), oral disorder, flatulence; hepatic enzyme abnormality; rash, pruritus, erythema, dry skin; muscle spasms, pain in extremity, muscular weakness; renal impairment; oedema (including peripheral), chills, pain, malaise; decreased wt.

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

Targeted Cancer Therapy

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

Rx