A-Z Drug Facts > Bortezomib

Bortezomib

Pronouncation: (bor-TEZ-oh-mib)
Class: Proteasome inhibitor

Trade Names:
Velcade
- Powder for injection, lyophilized 3.5 mg

Pharmacology

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Inhibits 26S proteasome, disrupting normal homeostatic mechanisms and leading to cell death.

Pharmacokinetics

Absorption

C _max is 89 to 120 ng/mL following IV administration of 1.3 mg/m ² .

Distribution

83% bound to plasma protein. Vd approximately 498 to 1,884 L/m ² .

Metabolism

In vitro studies indicate metabolism is primarily oxidative via CYP1A2, 2C9, 2C19, 2D6, and 3A4.

Elimination

The elimination pathways have not been characterized in humans.

Indications and Usage

Treatment of multiple myeloma or mantle cell lymphoma in patients who have received at least 1 prior therapy.

Contraindications

Hypersensitivity to boron, mannitol, or any component of the product.

Dosage and Administration

Adults

IV 1.3 mg/m ² /dose administered as a bolus twice/wk for 2 wk (days 1, 4, 8, and 11) followed by a 10-day rest period (days 12 to 21), which constitutes a 3-wk treatment cycle. At least 72 h should elapse between consecutive doses.

Reinstitution of Therapy
Adults

IV Withhold therapy at the onset of any grade 3 nonhematological or grade 4 hematological toxicities, excluding neuropathy discussed in the following dose modification section. Once symptoms of toxicity have resolved, reinitiate therapy at a 25% dose reduction (eg, 1.3 mg/m ² /dose reduced to 1 mg/m ² /dose).

Dose Modification
Adults

IV There is no dose modification for grade 1 peripheral neuropathy (paresthesias and/or loss of reflexes) without pain or loss of function. For grade 1 peripheral neuropathy with pain or grade 2 (interfering with function but not with activities of daily living), reduce dose to 1 mg/m ² . For grade 2 peripheral neuropathy with pain or grade 3 (interfering with activities of daily living), withhold therapy until toxicity resolves, then reinitiate therapy with a reduced dose of 0.7 mg/m ² and change treatment schedule to once weekly. Discontinue therapy for grade 4 (permanent sensory loss that interferes with function).

General Advice

• Follow manufacturer's instructions for reconstituting powder. Use caution during handling and preparation. Use gloves and other protective clothing to prevent skin contact.
• Inspect solution visually before administration. Do not administer if solution is cloudy, discolored, or contains particulate matter.
• Discard any unused product. Vials are for single-use only. Do not save medication for future use.

Storage/Stability

Store unopened vials at controlled room temperature (59° to 86°F) in original package to protect from light. Reconstituted solution may be stored at controlled room temperature for up to 8 h. Reconstituted solution may be stored for up to 8 h in syringe prior to administration; however, the total storage time for reconstituted solution must not exceed 8 h when exposed to indoor lighting.

Drug Interactions

CYP3A4 inducers (eg, carbamazapine)

Bortezomib plasma concentrations may be reduced; closely monitor patient for decreased bortezomib efficacy.

CYP3A4 inhibitors (eg, ketoconazole)

Bortezomib plasma concentrations may be increased; closely monitor patient for bortezomib toxicity.

Oral hypoglycemic agents (eg, glipizide)

Because hypoglycemia and hyperglycemia were reported in trials, adjustment of antidiabetic dosages may be necessary.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypotension (15%); aggravated atrial fibrillation, atrial flutter, cardiac amyloidosis, cardiac tamponade, CV accident, complete AV block, deep venous thrombosis, hemorrhagic stroke, MI, myocardial ischemia, peripheral embolism, pulmonary embolism, sinus arrest, torsades de pointes (postmarketing).

CNS

Asthenic conditions (61%); peripheral neuropathy (55%); psychiatric disorders, pyrexia (37%); paresthesia/dysesthesia (27%); headache (26%); dizziness (23%); insomnia (21%); anxiety (11%); ataxia, coma, dysarthria, dysautonomia, encephalopathy, generalized tonic-clonic seizures, herpes meningoencephalitis, neuralgia, paralysis, postherpetic neuralgia, psychotic disorder (postmarketing).

Dermatologic

Rash (28%); toxic epidermal necrolysis (postmarketing).

EENT

Nasopharyngitis (14%); bilateral deafness, ophthalmic herpes (postmarketing).

GI

Diarrhea, nausea (57%); constipation (50%); anorexia/decreased appetite (39%); vomiting (35%); abdominal pain (16%); acute pancreatitis, gastroesophageal reflux, hemorrhagic gastritis, ischemic colitis, perforation of the large intestine (postmarketing).

Genitourinary

Acute and chronic renal failure, glomerular nephritis, renal calculus.

Hematologic-Lymphatic

Thrombocytopenia (38%); anemia (30%); neutropenia (19%); disseminated intravascular coagulation, leukopenia, lymphopenia.

Hepatic

Cholestasis, hepatic hemorrhage, hepatitis, liver failure, portal vein thrombosis.

Metabolic-Nutritional

Dehydration (11%).

Musculoskeletal

Arthralgia (18%); bone pain (16%); back pain (15%); muscle cramps, myalgia (12%); rigors (11%); skeletal fracture.

Respiratory

Dyspnea (23%); cough (21%); lower respiratory tract/lung infections, upper respiratory tract infection (15%); pneumonia (12%); diffuse infiltrative pulmonary disease, exacerbation of chronic obstructive airways disease, pleural effusion, respiratory distress (postmarketing).

Miscellaneous

Edema (28%); limb pain (17%); herpes zoster (13%); lower limb edema (11%); anaphylactic reaction, angioedema, drug hypersensitivity, immune complex–mediated hypersensitivity, laryngeal edema, septic shock, subdural hematoma, toxoplasmosis.

Precautions

Monitor Monitor patient for symptoms of peripheral neuropathy (eg, burning sensation, hyperesthesia, paresthesia, discomfort, neuropathic pain). Notify health care provider if detected and be prepared to change the dose and dosing schedule of bortezomib according to manufacturer's recommendations. Monitor BP, especially in patients concurrently receiving medications known to lower BP. Be prepared to adjust dose of antihypertensive medication(s) if hypotension occurs. Frequently monitor CBC.

Pregnancy

Category D .

Lactation

Undetermined.

Children

Safety and efficacy not established.

Renal Function

Closely monitor for bortezomib toxicity.

Hepatic Function

Use with caution.

Closely monitor for bortezomib toxicity in patients with renal function impairment. Rarely, acute hepatic failure has been reported.

Cardiac disorders

Acute development or exacerbation of CHF and new onset of decreased left ventricular ejection fraction may occur.

GI

Constipation, diarrhea, nausea, and vomiting, sometimes requiring use of antiemetics and antidiarrheals, may occur.

Hypotension

Because orthostatic/postural hypotension can occur, use with caution in treating patients with a history of syncope, patients receiving medications known to be associated with hypotension, and patients who are dehydrated.

Peripheral neuropathy

Peripheral neuropathy that is predominantly sensory may occur, although severe sensory and motor perpheral neuropathy has been reported.

Reversible posterior leukoencephalopathy syndrome

Has been reported rarely.

Thrombocytopenia

May occur throughout therapy but is most common in cycles 1 and 2.

Tumor lysis syndrome

Because malignant cells may be killed rapidly, complications of tumor lysis syndrome may occur.

Patient Information

• Ensure that patient, family, or caregiver understands that medication is administered in treatment cycles.
• Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting.
• Advise patient that drug may cause fatigue, dizziness, fainting, and/or vision changes, and to use caution while driving or performing other tasks requiring alertness until tolerance is determined.
• Instruct breast-feeding women to discontinue breast-feeding while undergoing treatment.
• Advise patient to notify health care provider if any of the following occur: abnormal skin sensations, dizziness, fainting, fever, light-headedness, nerve pain, persistent vomiting or diarrhea, or other symptoms of infection.
• Instruct diabetic patients to monitor blood glucose more frequently during therapy and to inform health care provider of significant changes in readings.
• Advise patients regarding appropriate measures to avoid dehydration because therapy is associated with vomiting and diarrhea.

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