Overview
11 DESCRIPTION Bortezomib for injection, a proteasome inhibitor, contains bortezomib which is an antineoplastic agent. Bortezomib is a modified dipeptidyl boronic acid. The chemical name for bortezomib, the monomeric boronic acid, is [(1R)-3-methyl-1-[[(2S)-1-oxo-3-phenyl-2-[(pyrazinylcarbonyl) amino]propyl]amino]butyl] boronic acid.
Mechanism of Action
12 CLINICAL PHARMACOLOGY 12.1 Mechanism of Action Bortezomib 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 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 .
Indications
- 1 INDICATIONS AND USAGE Bortezomib for injection is a proteasome inhibitor indicated for: • treatment of adult patients with multiple myeloma ( 1.1 ) • treatment of adult patients with mantle cell lymphoma ( 1.2 ) 1.1 Multiple Myeloma Bortezomib for injection is indicated for the treatment of adult patients with multiple myeloma. 1.2 Mantle Cell Lymphoma Bortezomib for injection is indicated for the treatment of adult patients with mantle cell lymphoma.
Common Doses
- 1.3 mg
- 1 mg
- 2.5 mg
- 9 mg
Dosage
2 DOSAGE AND ADMINISTRATION • For subcutaneous or intravenous use only. Each route of administration has a different reconstituted concentration. Exercise caution when calculating the volume to be administered. ( 2.1 , 2.10 ) • The recommended starting dose of bortezomib for injection is 1.3 mg/m 2 administered either as a 3 to 5 second bolus intravenous injection or subcutaneous injection. ( 2.2 , 2.4 , 2.6 ) • Retreatment for Multiple Myeloma: May retreat starting at the last tolerated dose. ( 2.
Contraindications
- 4 CONTRAINDICATIONS Bortezomib is contraindicated in patients with hypersensitivity (not including local reactions) to bortezomib, boron, or mannitol. Reactions have included anaphylactic reactions [see Adverse Reactions ( 6.1 )]. Bortezomib is contraindicated for intrathecal administration. Fatal events have occurred with intrathecal administration of bortezomib. • Patients with hypersensitivity (not including local reactions) to bortezomib, boron, or mannitol, including anaphylactic reactions. ( 4 ) • Contraindicated for intrathecal administration. ( 4 )
Side Effects
- 6 ADVERSE REACTIONS The following clinically significant adverse reactions are also discussed in other sections of the labeling: • Peripheral Neuropathy [see Warnings and Precautions ( 5.1 )] • Hypotension [see Warnings and Precautions ( 5.2 )] • Cardiac Toxicity [see Warnings and Precautions ( 5.3 )] • Pulmonary Toxicity [see Warnings and Precautions ( 5.4 )] • Posterior Reversible Encephalopathy Syndrome (PRES) [see Warnings and Precautions ( 5.5 )] • Gastrointestinal Toxicity [see Warnings and Precautions ( 5.6 )] • Thrombocytopenia/Neutropenia [see Warnings and Precautions ( 5.
Interactions
- 7 DRUG INTERACTIONS • Strong CYP3A4 Inhibitors: Closely monitor patients with concomitant use. ( 7.1 ) • Strong CYP3A4 Inducers: Avoid concomitant use. (7.3) 7.1 Effects of Other Drugs on Bortezomib Strong CYP3A4 Inducers Coadministration with a strong CYP3A4 inducer decreases the exposure of bortezomib [see Clinical Pharmacology ( 12.3 )] which may decrease bortezomib efficacy. Avoid coadministration with strong CYP3A4 inducers. Strong CYP3A4 Inhibitors Coadministration with a strong CYP3A4 inhibitor increases the exposure of bortezomib [see Clinical Pharmacology ( 12.