bortezomib


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bortezomib

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, patients with mantle cell lymphoma who have received at least one prior therapy

Adults: 1.3 mg/m2 I.V. or subcutaneously 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).

Dosage adjustment

• Moderate or severe hepatic impairment

• Peripheral neuropathy

• Grade 3 nonhematologic events

• Grade 4 hematologic events

Contraindications

• Hypersensitivity to drug, mannitol, or boron

Precautions

Use cautiously in:

• peripheral neuropathy, dehydration, hepatic or renal impairment

• history of syncope or cardiovascular disorders

• pregnant or breastfeeding patients

• children.

Administration

• Be aware that drug is for I.V. or subcutaneous use only. Because each route of administration has a different reconstituted concentration, use caution when calculating volume to be administered.

• Reconstitute drug in vial with 3.5 ml of normal saline for injection to yield a concentration of 1 mg/ml for I.V. use.

• Reconstitute drug in vial with 1.4 ml of normal saline for injection to yield a concentration of 2.5 mg/ml for subcutaneous use.

• Give by I.V. push over 3 to 5 seconds or subcutaneously.

• Reconstituted solution must be used within 8 hours.

Adverse reactions

CNS: headache, insomnia, dizziness, anxiety, peripheral neuropathy, reversible posterior leukoen-cephalopathy syndrome

CV: tachycardia, hypotension

EENT: throat tightness

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

Hematologic: eosinophilia, anemia, thrombocytopenia, neutropenia

Hepatic: hyperbilirubinemia, hepatitis, acute liver failure

Metabolic: dehydration, pyrexia

Respiratory: cough, dyspnea, upper respiratory tract infection, acute diffuse infiltrative pulmonary disease (pneumonitis, interstitial pneumonia, acute respiratory distress syndrome)

Skin: rash, pruritus, urticaria

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

Interactions

Drug-drug. CYP3A4 inducers (including amiodarone, carbamazepine, nevi-rapine, 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-diagnostic tests. Liver function

tests: increased levels

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.

Stay alert for and discontinue drug if posterior leukoencephalopathy (headache, seizures, lethargy, confusion, blindness) or tumor lysis syndrome occurs (irregular heartbeat, shortness of breath, high potassium level, high uric acid level, impairment of mental ability, kidney failure).

Closely monitor liver function tests and watch for signs and symptoms of hepatitis or liver failure.

• 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 that drug may cause other significant adverse reactions. Reassure him he will be closely monitored.

• Instruct patient to move slowly when sitting or standing up to avoid dizziness or light-headedness from sudden blood pressure drop.

• 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.

bortezomib

A proteasome inhibitor which induces apoptosis in cancer cells, and inhibits binding to stromal cells and production of growth and survival factors.

Indications
Treatment-refractory myeloma (35% response rate), mantle cell lymphoma.
 
Adverse effects
Thrombocytopaenia, fatigue, peripheral neuropathy, neutropaenia. 

bortezomib

The first of a new class of anticancer drugs that act by inhibition of the action of PROTEASOMES. When proteasomes in tumour cells are inhibited, these cells become greatly sensitized to the action of cytotoxic drugs. The drug has been found to produce a 35 per cent response rate in patients with relapsed and refractive multiple MYELOMATOSIS. A brand name is Velcade.
References in periodicals archive ?
Neurotoxicity of bortezomib therapy in multiple myeloma: a single-center experience and review of the literature.
In July 2012, the FDA granted approval of carfilzomib for the treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an immunomodulatory drug and who have shown disease progression while on therapy or within 60 days of completion of the last therapy.
We demonstrate this effect with two different proteasome inhibitors, bortezomib and ixazomib, indicating the potential generality of the approach.
While the rapid therapeutic response and improvement in the markers of MM activity are typical after bortezomib therapy, there are few data on the reduction in the size of ostelytic bone lesions and increase in the bone fraction of AP.
However, three patients received rituximab between 2010 and 2013 because of a diagnosis of preexisting polyneuropathy, which is a well-known side effect and consequently a contraindication for bortezomib treatment.
He was diagnosed with MM and was treated with five cycles of Cyclophosphamide, Bortezomib, and Dexamethasone (CYBOR-D) prior to undergoing an autologous stem cell transplant (ASCT).
Gavriatopoulou et al., "Primary therapy of Waldenstrom macroglobulinemia (WM) with weekly bortezomib, low-dose dexamethasone, and rituximab (BDR): long-term results of a phase 2 study of the European Myeloma Network (EMN)," Blood, vol.
These new therapies used bortezomib, a drug already approved by the US Food and Drug Administration (FDA) for treatment of multiple myeloma, a type of cancer, said the study appeared in the American Journal of Transplantation.
AbbVie has initiated a Phase III trial to study the safety and efficacy of venetoclax in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma who are considered sensitive or naive to proteasome inhibitors and have received one to three prior lines of therapy.
En 2008 la Administracion de Alimentos y Medicamentos de Estados Unidos (Food and Drug Administration FDA) aprobo el uso de bortezomib, para el tratamiento de mieloma multiple.