Velcade: Full Drug Profile
Velcade - General Information
Velcade (originally PS-341 and marketed as Velcade by Millennium Pharmaceuticals) is the first therapeutic proteasome inhibitor to be tested in humans. It is approved in the U.S. for treating relapsed multiple myeloma and mantle cell lymphoma. In multiple myeloma, complete clinical responses have been obtained in patients with otherwise refractory or rapidly advancing disease.
Pharmacology of Velcade
Velcade is a drug that inhibits the mammalian 26S proteasome. The ubiquitin-proteasome pathway plays an essential role in regulating the intracellular concentration of specific proteins, thereby maintaining homeostasis within cells. Inhibition of the 26S proteasome prevents this targeted proteolysis, which can affect multiple signaling cascades within the cell. This disruption of normal homeostatic mechanisms can lead to cell death. Experiments have demonstrated that bortezomib is cytotoxic to a variety of cancer cell types in vitro. Velcade causes a delay in tumor growth in vivo in nonclinical tumor models, including multiple myeloma. Tumor cells, that is, rapidly dividing cells, appear to be more sensitive to proteasome inhibition.
Velcade for patients
VELCADE (bortezomib) for Injection
PATIENT INFORMATION
VELCADE is intended for use under the guidance and supervision of a healthcare professional. Please discuss the possibility of the following side effects with your doctor:
Effects on Ability to Drive or Operate Machinery or Impairment of Mental Ability: VELCADE may cause low blood pressure that may lead to tiredness, dizziness, fainting, or blurred vision. Do not drive any vehicle or operate any dangerous tools or machinery if you experience these side effects. Even if you have not felt these effects previously, you must still be cautious.
Pregnancy/Nursing: Please use effective contraceptive measures to prevent pregnancy during treatment with VELCADE. It is advised that you are not given VELCADE if you are pregnant. You must make sure that you do not become pregnant while receiving VELCADE, but if you do, inform your doctor immediately. It is advised that you do not breast feed while you are receiving VELCADE. If you wish to restart breast feeding after your VELCADE treatment, you must discuss this with your doctor or nurse, who will tell you when it is safe to do so.
Dehydration/Hypotension: Following the use of VELCADE therapy, you may experience vomiting and/or diarrhea. Drink plenty of fluids. Speak with your doctor if these symptoms occur about what you should do to control or manage these symptoms. If you experience symptoms of dizziness or light-headedness, consult a healthcare professional. Seek immediate medical attention if you experience fainting spells.
Concomitant Medications: Please speak with your doctor about any other medication you are currently taking. Your doctor will want to be aware of any other medications.
Diabetic Patients: If you are a patient on oral antidiabetic medication while receiving VELCADE treatment, please check your blood sugar level frequently. Please call your doctor if you notice an unusual change.
Peripheral Neuropathy: Contact your doctor if you experience new or worsening symptoms of peripheral neuropathy such as tingling, numbness, pain, or a burning feeling in the feet or hands.
Congestive Heart Failure: Contact your doctor if you experience shortness of breath or swelling of the feet, ankles, or legs.
Velcade Interactions
No formal drug interaction studies have been conducted with VELCADE.
In vitro studies with human liver microsomes indicate that bortezomib is primarily a substrate for cytochrome P450 3A4, 2C19, and 1A2. Patients who are concomitantly receiving VELCADE and drugs that are inhibitors or inducers of cytochrome P450 3A4 should be closely monitored for either toxicities or reduced efficacy.
During clinical trials, hypoglycemia and hyperglycemia were reported in diabetic patients receiving oral hypoglycemics. Patients on oral antidiabetic agents receiving VELCADE treatment may require close monitoring of their blood glucose levels and adjustment of the dose of their antidiabetic medication.
Drug Laboratory Test Interactions
None known.
Velcade Contraindications
VELCADE is contraindicated in patients with hypersensitivity to bortezomib, boron, or mannitol.
Additional information about Velcade
Velcade Indication: For treatment of multiple myeloma in patients who have not been successfully treated with at least two previous therapies. Mechanism Of Action: Velcade is a reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome in mammalian cells. The 26S proteasome is a large protein complex that degrades ubiquitinated proteins. The active site of the proteasome has chymotrypsin-like, trypsin-like, and postglutamyl peptide hydrolysis activity. The 26S proteasome degrades various proteins critical to cancer cell survival, such as cyclins, tumor suppressors, BCL-2, and cyclin-dependent kinase inhibitors. Inhibition of these degradations sensitizes cells to apoptosis. Velcade is a potent inhibitor of 26S proteasome, which sensitizes activity in dividing multiple myeloma and leukemic cells, thus inducing apoptosis. In addition, bortezomib appears to increase the sensitivity of cancer cells to traditional anticancer agents (e.g., gemcitabine, cisplatin, paclitaxel, irinotecan, and radiation). Drug Interactions: Not Available Food Interactions: Not Available Generic Name: Bortezomib Synonyms: Not Available Drug Category: Antineoplastic Agents; Protease Inhibitors Drug Type: Small Molecule; Approved; Investigational Other Brand Names containing Bortezomib: Velcade; Absorption: Not Available Toxicity (Overdose): Cardiovascular safety pharmacology studies in monkeys show that lethal IV doses are associated with decreases in blood pressure, increases in heart rate, increases in contractility, and ultimately terminal hypotension. In monkeys, doses of 3.0 mg/m2 and greater (approximately twice the recommended clinical dose) resulted in progressive hypotension starting at 1 hour and progressing to death by 12 to 14 hours following drug administration. Protein Binding: 83% over the concentration range of 100-1000 ng/ml. Biotransformation: In vitro studies with human liver microsomes and human cDNA-expressed cytochrome P450 isozymes indicate that bortezomib is primarily oxidatively metabolized via cytochrome P450 enzymes 3A4, 2C19, and 1A2, while bortezomib metabolism by CYP 2D6 and 2C9 enzymes is minor. The major metabolic pathway is deboronation to form 2 deboronated metabolites that subsequently undergo hydroxylation to several metabolites which are inactive as 26S proteasome inhibitors. Half Life: The mean elimination half-life of bortezomib after first dose ranged from 9 to 15 hours at doses ranging from 1.45 to 2.00 mg/m2 in patients with advanced malignancies. Dosage Forms of Velcade: Powder, for solution Intravenous Chemical IUPAC Name: [(1S)-3-methyl-1-[[(2R)-3-phenyl-2-(pyrazine-2-carbonylamino)propanoyl]amino]butyl]boronic acid Chemical Formula: C19H25BN4O4 Bortezomib on Wikipedia: https://en.wikipedia.org/wiki/Bortezomib Organisms Affected: Humans and other mammals