bortezomib

(C) Vancouver General Hospital.
This monograph may not be reproduced without permission.
For further information, please contact a Pharmacist.

NAME OF DRUG
bortezomib

CLASSIFICATION

Cytotoxic Agent - non-vesicant

ALTERNATE NAMES

VELCADE

INDICATIONS

treatment of refractory multiple myeloma

PHARMACOLOGY

reversible inhibitor of the 26S proteasome resulting in cell cycle arrest and cell death
metabolized via cytochrome p450 enzymes (primarily 3A4 and 2C19) to inactive metabolites; clearance may be reduced in patients with hepatic impairment
elimination half-life ranges from 9-15 hours

RECONSTITUTION AND STABILITY

ALL cytotoxic agents are prepared in pharmacy and will be sent to the ward with a label indicating storage conditions and the expiry date. All cytotoxic waste including bags, sets, tubing, gloves, etc. must be properly disposed of in the cytotoxic waste containers on the nursing unit.
store reconstituted solution at room temperature
administer within 8 hours of preparation

COMPATIBILITY

compatible with NS only
do not mix with other drugs or IV solutions

ROUTES OF ADMINISTRATION

IV direct – over 3-5 seconds via peripheral or central line

VH & HSC ADMINISTRATION POLICY

Restricted to approval by BCCA

A Parenteral Chemotherapy/Immunotherapy pre-printed order form (PPO # 45) must be used for prescribing if this cytotoxic agent is not already on an existing PPO.

G - Cytotoxic Agents - See Drug Table G for specific administration guidelines.

DOSAGE

1.3 mg/m2 twice weekly for 2 weeks (days 1, 4, 8 and 11) followed by a 10-day rest period (days 12-21); at least 72 hours should elapse between consecutive doses
adjust dosage as per Table below:

Condition	Dosage Adjustment
Hematological Toxicities	At the onset of any NCI Grade 4 hematological toxicities including platelet count < 25 x 10⁹/L, discontinue the drug until symptoms resolve; reinitiate at a 25% dose reduction
Neuropathy	Grade 1 without pain or loss of function: maintain dose Grade 1 with pain or Grade 2: reduce dose by 25% Grade 2 with pain or Grade 3: withhold treatment until symptoms resolve; reinitiate at 0.7 mg/m² once weekly Grade 4: discontinue bortezomib
Diarrhea	< Grade 2 (4-6 stools/day): no change from previous cycle > Grade 3 (7-9 stools/day or associated mucus or dehydration: reduce dose by 20-25% of that used in the last course
Other Non- hemotological Toxicities	At the onset of any NCI Grade 3 non-hematological toxicities, discontinue bortezomib until symptoms resolve; reinitiate at a 25% dose reduction

Hepatic Failure: Use with caution; dose modification should be considered since the drug is metabolized by liver enzymes
Renal Failure: Use with caution; has been given safely to patients on hemodialysis

POTENTIAL HAZARDS OF PARENTERAL ADMINISTRATION

extravasation (see Appendix VII for extravasation protocol of non-vesicants)
rash (28%), pruritis (12%), hypersensitivity (rare)
fever

IMPORTANT IMPLICATIONS

monitor CBC prior to each dose - thrombocytopenia nadir day 11
evaluate patients for possible toxicities as listed below BEFORE each dose
major toxicities include peripheral neuropathy (pain, burning sensation, numbness), cardiovascular effects (orthostatic hypotension, CHF, myocardial infarction), GI effects (nausea, diarrhea, constipation, vomiting), hematologic (thrombocytopenia, neutropenia, anemia)
most common adverse effects include painful sensations or numbness and tingling in hands or feet (may not resolve after discontinuation), nausea, diarrhea, decreased appetite, constipation, vomiting, fever, thrombocytopenia and anemia, fatigue, malaise, weakness, cough
less common include deterioration of liver or renal function, severe bleeding, tumour lysis syndrome
drugs which may potentially increase toxicity of bortezomib (inhibit metabolism): erythromycin, ketoconazole; drugs which may potentially decrease efficacy of bortezomib (enzyme inducers): phenytoin

September 2006