BDLYPO Dosage/Direction for Use

BDLYPO should only be administered under the supervision of a qualified oncologist specialised in the administration of cytotoxic agents.
It exhibits unique pharmacokinetic properties and must not be used interchangeably with other formulations of doxorubicin hydrochloride.
It is administered intravenously at a dose of 50 mg/m² once every 4 weeks for as long as the disease does not progress and the patient continues to tolerate treatment.
It is administered at 30 mg/m² on day 4 of the bortezomib 3 week regimen as a 1 hour infusion administered immediately after the bortezomib infusion. The bortezomib regimen consists of 1.3 mg/m² on days 1, 4, 8, and 11 every 3 weeks. The dose should be repeated as long as patients respond satisfactorily and tolerate treatment. Day 4 dosing of both medicinal products may be delayed up to 48 hours as medically necessary. Doses of bortezomib should be at least 72 hours apart.
DOSAGE MODIFICATIONS: Because drugs exhibits nonlinear pharmacokinetics at 50 mg/m², dosage adjustments may cause non-proportionally greater change in plasma level and drug exposure.
If grade 2 or higher adverse events occur, decreases dosage or delay therapy; do not increase dosage later.
In hepatic impairment, reduce normal dosage by 50% if serum bilirubin level is 1.2 to 3 mg/dL or by 25% if bilirubin level exceeds 3 mg/dL.
MODIFICATIONS ACCORDING TO TOXICITY LEVEL: Grade 1 palmar-plantar erythrodysesthesia [hand-foot syndrome (HFSI)]: Continue dosing. If patient previously had Grade 3 or 4 toxicity, delay dosing up to 2 weeks and decrease dosage by 25%.
Grade 2 HFS: Delay dosing up to 2 weeks or until resolved to Grade 0 to 1. If no resolution occurs after 2 weeks, discontinue drug. If resolved to Grade 0 to 1 within 2 weeks and there are no Grade 3 to 4 HFS toxicities, continue treatment at previous dosage and return to original dosing interval. If patient previously experienced Grade 3 to 4 toxicity, continue treatment with 25% dosage reduction and return to original dosing interval.
Grade 3 HFS: Delay dosing up to 2 weeks or until resolved to Grade 0 to 1. Decrease dosage by 25% and return to original dosing interval. If no resolution occurs after 2 weeks, discontinue drug.
Grade 4 HFS: Delay dosing up to 2 weeks or until resolved to Grade 0 to 1. Decrease dosage by 25% and return to original dosing interval. If no resolution occurs after 2 weeks, discontinue drug.
Grade 1 hematologic toxicity (absolute neutrophil count [ANC] 1,500 to 1,900/mm³; platelets, 75,000 to 150,000/mm³); No dosage reduction is necessary.
Grade 2 hematologic toxicity (ANC 1,000 to less than 1,500/mm³, platelets, 50,000 to less than 75,000/mm³): Wait until ANC is 1,500/mm³ or above and platelet count is 75,000/mm³ or above, then redose with no dosage reduction.
Grade 4 hematologic toxicity (ANC below 500/mm³; platelets below 25,000/mm³): Wait until ANC is 1500/mm³; or above and platelet count is 75,000/mm³ or above, then redose at 25% dosage reduction or continue full dose with cytokine support.
Grade 1 stomatitis: Redose unless patient experienced previous Grade 3 or 4 toxicity. If so, delay dosing up to 2 weeks and decrease dosage by 25%. Return to original dosing interval.
Delay dosing up to 2 weeks or until resolved to Grade 0 to 1. If no resolution occurs after 2 weeks, discontinue drug. If resolved to Grade 0 to 1 within 2 weeks and there is no Grade 3 to 4 stomatitis, continue treatment at previous dosage and return to original dosing interval. If patients previously experienced Grade 3 to 4 toxicity, continue treatment with 25% dosage reduction and return to original dosing interval.
Grade 3 stomatitis: Delay dosing up to 2 weeks or until resolved to Grade 0 to 1. Decrease dosage by 25% dosage reduction and return to original dosing interval. If no resolution occurs after 2 weeks, discontinue drug.
Grade 4 stomatitis: Delay dosing up to 2 weeks or until resolved to Grade 0 to 1. Decrease dosage by 25% and return to original dosing interval. If no resolution occurs after 2 weeks, discontinue drug.