Velcade

Monotherapy or in combination w/ pegylated liposomal doxorubicin or dexamethasone for the treatment of progressive multiple myeloma in adults who have received at least 1 prior therapy & who have already undergone or are unsuitable for haematopoietic stem cell transplantation. In combination w/ melphalan & prednisone for the treatment of previously untreated multiple myeloma in adults who are not eligible for high-dose chemotherapy w/ haematopoietic stem cell transplantation. In combination w/ dexamethasone, or w/ dexamethasone & thalidomide, for the induction treatment of previously untreated multiple myeloma in adults who are eligible for high-dose chemotherapy w/ haematopoietic stem cell transplantation. In combination w/ rituximab, cyclophosphamide, doxorubicin & prednisone for the treatment of previously untreated mantle cell lymphoma in adults who are unsuitable for haematopoietic stem cell transplantation.

Administer Velcade 1.3 mg/m² as 3-5 sec bolus IV inj or as SC inj. At least 72 hr should elapse between consecutive Velcade doses. Progressive multiple myeloma (monotherapy) Administer Velcade twice wkly for 2 wk on days 1, 4, 8, & 11 in a 21-day treatment cycle. This 3-wk period is considered a treatment cycle. Patients should receive 2 cycles following confirmation of complete response. Responding patients who do not achieve complete remission should receive a total of 8 cycles. Progressive multiple myeloma (combination therapy w/ pegylated liposomal doxorubicin) Administer Velcade twice wkly for 2 wk on days 1, 4, 8, & 11 in a 21-day treatment cycle. This 3-wk period is considered a treatment cycle. Administer pegylated liposomal doxorubicin 30 mg/m² on day 4 of Velcade treatment cycle as 1 hr IV infusion after Velcade inj. Up to 8 cycles of this combination therapy can be administered as long as patients have not progressed & tolerate treatment. Patients achieving complete response can continue treatment for at least 2 cycles after the 1st evidence of complete response, even if this requires treatment for >8 cycles. Patients whose paraprotein levels continue to decrease after 8 cycles can also continue for as long as treatment is tolerated & they continue to respond. Progressive multiple myeloma (combination therapy w/ dexamethasone) Administer Velcade twice wkly for 2 wk on days 1, 4, 8, & 11 in a 21-day treatment cycle. This 3-wk period is considered a treatment cycle. Administer dexamethasone 20 mg orally on days 1, 2, 4, 5, 8, 9, 11, & 12 of Velcade treatment cycle. Patients achieving response or stable disease after 4 cycles of this combination therapy can continue to receive the same combination for a max of 4 additional cycles. Previously untreated multiple myeloma not eligible for haematopoietic stem cell transplantation Administer Velcade twice wkly on days 1, 4, 8, 11, 22, 25, 29, & 32 in cycles 1-4, & once wkly on days 1, 8, 22, & 29 in cycles 5-9. A 6-wk period is considered a treatment cycle. Administer melphalan 9 mg/m² & prednisone 60 mg/m² orally on days 1, 2, 3, & 4 of the 1st wk of each Velcade treatment cycle. Administer 9 treatment cycles of this combination therapy. Previously untreated multiple myeloma eligible for haematopoietic stem cell transplantation (combination therapy w/ dexamethasone) Administer Velcade twice wkly for 2 wk on days 1, 4, 8, & 11 in a 21-day treatment cycle. This 3-wk period is considered a treatment cycle. Administer dexamethasone 40 mg orally on days 1, 2, 3, 4, 8, 9, 10, & 11 of Velcade treatment cycle. Administer 4 treatment cycles of this combination therapy. Previously untreated multiple myeloma eligible for haematopoietic stem cell transplantation (combination therapy w/ dexamethasone & thalidomide) Administer Velcade twice wkly for 2 wk on days 1, 4, 8, & 11 in a 28-day treatment cycle. This 4-wk period is considered a treatment cycle. Administer dexamethasone 40 mg orally on days 1, 2, 3, 4, 8, 9, 10, & 11 of Velcade treatment cycle. Administer thalidomide 50 mg daily orally on days 1-14, then increase to 100 mg on days 15-28 if tolerated, & may further increase to 200 mg daily from cycle 2 thereafter. Administer 4 treatment cycles of this combination therapy. Patients w/ at least partial response should receive 2 additional cycles. Previously untreated mantle cell lymphoma Administer Velcade twice wkly for 2 wk on days 1, 4, 8, & 11, followed by a 10-day rest period on days 12-21. This 3-wk period is considered a treatment cycle. 6 cycles are recommended, although for patients w/ response 1st documented at cycle 6, 2 additional cycles may be given. Administer rituximab 375 mg/m², cyclophosphamide 750 mg/m², & doxorubicin 50 mg/m² on day 1 of each Velcade treatment cycle as IV infusions. Administer prednisone 100 mg/m² orally on days 1, 2, 3, 4, & 5 of each Velcade treatment cycle. Patient w/ moderate or severe hepatic impairment Reduce to 0.7 mg/m² in the 1st treatment cycle. Consider dose escalation to 1 mg/m² or further dose reduction to 0.5 mg/m² in subsequent cycles based on patient tolerability.

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

Do not administer intrathecally. Rotate inj sites for successive SC inj. Either subcutaneously administer a less concentrated soln or switch to IV inj if local inj site reactions occur following SC inj. Risk of GI toxicity, including nausea, diarrhoea, vomiting & constipation; haematological toxicities (thrombocytopenia, neutropenia & anaemia); HZV reactivation; HBV reactivation & infection; progressive multifocal leukoencephalopathy (PML); peripheral neuropathy, predominantly sensory; seizures; orthostatic/postural hypotension; posterior reversible encephalopathy syndrome (PRES); acute development or exacerbation of CHF, &/or new onset of decreased left ventricular ejection fraction; QT-interval prolongation; acute diffuse infiltrative pulmonary disease of unknown aetiology eg, pneumonitis, interstitial pneumonia, lung infiltration, & acute resp distress syndrome; hepatic reactions, including hepatic failure, increased liver enzymes, hyperbilirubinaemia & hepatitis; tumour lysis syndrome; potentially immunocomplex-mediated reactions eg, serum-sickness-type reaction, polyarthritis w/ rash & proliferative glomerulonephritis. Monitor platelet counts prior to each dose. Frequently monitor CBC w/ differential & platelet counts throughout treatment. W/hold therapy when platelet count is <25,000/microlitre or, in the case of combination w/ melphalan & prednisone, when platelet count is ≤30,000/microlitre. Antiviral prophylaxis is recommended in patients on Velcade treatment. Always perform HBV screening in patients at risk of HBV infection before treatment initiation when used in combination w/ rituximab. Closely monitor hepatitis B carriers & patients w/ history of hepatitis B for clinical & lab signs of active HBV infection during & following combination treatment w/ rituximab. Discontinue treatment if PML is diagnosed. Consider early & regular monitoring for symptoms of treatment-emergent neuropathy w/ neurological evaluation in patients receiving Velcade in combination w/ medicinal products associated w/ neuropathy (eg, thalidomide), & consider appropriate dose reduction or treatment discontinuation. Caution when treating patients w/ history of syncope who are receiving medicinal products associated w/ hypotension or who are dehydrated due to recurrent diarrhoea or vomiting. Discontinue treatment in patients developing PRES. Consider benefit/risk ratio prior to continuing therapy in the event of new or worsening pulmonary symptoms. Discontinue treatment if serious potentially immunocomplex-mediated reactions occur. Closely monitor when combined w/ potent CYP3A4 inhibitors. Exercise caution when combined w/ CYP3A4 or CYP2C19 substrates. Confirm normal liver function & exercise caution in patients receiving oral hypoglycemics. Moderate influence on the ability to drive & use machines. Unknown if pharmacokinetics are influenced in patients w/ severe renal impairment not undergoing dialysis (CrCl <20 mL/min/1.73 m²). Increased exposure in patients w/ moderate or severe hepatic impairment. Male & female patients of childbearing potential must use effective contraception during & for 3 mth following treatment. Do not use during pregnancy unless clinical condition of the woman requires treatment. Patients receiving Velcade in combination w/ thalidomide should adhere to the pregnancy prevention programme of thalidomide. Discontinue breastfeeding during treatment. Safety & efficacy in childn <18 yr have not been established.

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

Increased AUC w/ potent CYP3A4 inhibitors (eg, ketoconazole, ritonavir). Reduced AUC w/ strong CYP3A4 inducers (eg, rifampicin, carbamazepine, phenytoin, phenobarb, St. John's wort). Closely monitor blood glucose levels & adjust antidiabetic dose in patients on oral antidiabetics receiving Velcade treatment.

Targeted Cancer Therapy

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

P₁S₁S₃