bortezomib

bortezomib,

a miscellaneous antineoplastic.

indications This drug is used to treat multiple myeloma when at least two other treatments have failed.

contraindications Pregnancy and known hypersensitivity to this drug, boron, or Mannitol prohibit its use.

adverse effects Adverse effects of this drug include hypotension, edema, anemia, fatigue, malaise, weakness, arthralgia, bone pain, muscle cramps, myalgia, back pain, abdominal pain, constipation, diarrhea, dyspepsia, nausea, vomiting, anorexia, anxiety, insomnia, dizziness, headache, peripheral neuropathy, rigors, paresthesia, cough, pneumonia, dyspnea, upper respiratory infection, dehydration, weight loss, herpes zoster, rash, pruritus, and blurred vision. Life-threatening side effects include neutropenia and thrombocytopenia.

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bortezomib Warning - Hazardous drug!

Velcade

Pharmacologic class: Proteasome inhibitor

Therapeutic class: Antineoplastic

Pregnancy risk category D

Action

Inhibits proteasomes (enzyme complexes that regulate protein homeostasis within cells). Reversibly inhibits chymotrypsin-like activity at 26S proteasome, leading to activation of signaling cascades, cell-cycle arrest, and apoptosis.

Availability

Powder for reconstitution (preservative-free): 3.5 mg (contains 35 mg of mannitol)

⊘Indications and dosages

➣ Multiple myeloma in patients who have undergone at least two previous therapies and demonstrated disease progression during previous therapy

Adults: 1.3 mg/m² I.V. twice weekly for 2 weeks (days 1, 4, 8, and 11), followed by 10-day rest period (days 12 to 21). Allow at least 72 hours to elapse between doses. One treatment cycle equals 21 days (3 weeks).

Contraindications

• Hypersensitivity to drug, mannitol, or boron
• Pregnancy or breastfeeding

Precautions

Use cautiously in:
• peripheral neuropathy, dehydration, hepatic or renal impairment
• history of syncope or cardiovascular disorders
• children.

Administration

• Reconstitute drug in vial with 3.5 ml of normal saline for injection.
• Give by I.V. push over 3 to 5 seconds.
• Reconstituted solution must be used within 8 hours.

Route	Onset	Peak	Duration
I.V.	Unknown	Unknown	Unknown

Adverse reactions

CNS: headache, insomnia, dizziness, anxiety, peripheral neuropathy

CV: tachycardia, hypotension

EENT: throat tightness

GI: nausea, vomiting, diarrhea, abdominal pain, dyspepsia

Hematologic: eosinophilia, anemia, thrombocytopenia, neutropenia

Metabolic: dehydration, pyrexia

Respiratory: cough, dyspnea, upper respiratory tract infection

Skin: rash, pruritus, urticaria

Other: altered taste, increased or decreased appetite, fever, chills, edema

Interactions

Drug-drug. CYP3A4 inducers (including amiodarone, carbamazepine, nevirapine, phenobarbital, phenytoin, and rifampin): possible decrease in bortezomid serum level and efficacy CYP3A4 inhibitors (including amiodarone, cimetidine, clarithromycin, delavirdine, diltiazem, disulfiram, erythromycin, fluoxetine, fluvoxamine, nefazodone, nevirapine, propoxyphene, quinupristin, verapamil, zafirlukast, and zileuton): possible increase in bortezomib serum level and efficacy

Drug-food. Grapefruit juice: increased bortezomib blood level, greater risk of toxicity

Patient monitoring

☞ Monitor vital signs and temperature. Especially watch for tachycardia, fever, and hypotension.
• Monitor nutritional and hydration status for changes caused by GI adverse effects.
• Monitor CBC with white cell differential, and watch for signs and symptoms of blood dyscrasias.
• Monitor respiratory status, watching for dyspnea, cough, and other signs and symptoms of upper respiratory tract infection.

Patient teaching

☞ Inform patient that drug can cause serious blood dyscrasias. Teach him which signs and symptoms to report right away.
• Tell patient drug may cause other significant adverse reactions. Reassure him he will be closely monitored.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• Advise patient to minimize adverse GI effects by eating small frequent servings of healthy food and ensuring adequate fluid intake.
• Tell patient to immediately report signs and symptoms of upper respiratory tract infection.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and foods mentioned above.