Bortezomib

What it is and how it works

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 .

Mechanism class: Proteasome Inhibitors

Indications

Bortezomib for injection is a proteasome inhibitor indicated for: • treatment of adult patients with multiple myeloma • treatment of adult patients with mantle cell lymphoma Multiple Myeloma Bortezomib for injection is indicated for the treatment of adult patients with multiple myeloma. Mantle Cell Lymphoma Bortezomib for injection is indicated for the treatment of adult patients with mantle cell lymphoma.

Dosage and administration (summary)

• 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. • Hepatic Impairment: Use a lower starting dose for patients with moderate or severe hepatic impairment. • Dose must be individualized to prevent overdose.

Contraindications

Bortezomib is contraindicated in patients with hypersensitivity (not including local reactions) to bortezomib, boron, or mannitol. Reactions have included anaphylactic reactions . 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. • Contraindicated for intrathecal administration.

Warnings and precautions

• Peripheral Neuropathy: Manage with dose modification or discontinuation. Patients with pre-existing severe neuropathy should be treated with bortezomib only after careful risk-benefit assessment. ( 2.7 , 5.1 ) • Hypotension: Use caution when treating patients taking anti hypertensives, with a history of syncope, or with dehydration. • Cardiac Toxicity: Worsening of and development of cardiac failure has occurred. Closely monitor patients with existing heart disease or risk factors for heart disease. • Pulmonary Toxicity: Acute respiratory syndromes have occurred.

Pregnancy

Pregnancy Risk Summary Based on its mechanism of action and findings in animals, bortezomib can cause fetal harm when administered to a pregnant woman. There are no studies with the use of bortezomib in pregnant women to inform drug-associated risks.

Storage and supply

Each single-dose vial of bortezomib contains 3.5 mg of bortezomib as white to off-white lyophilized powder. NDC 31722-303-31 3.5 mg single-dose vial Unopened vials may be stored at controlled room temperature 25ºC (77ºF); excursions permitted from 15ºC to 30ºC (59ºF to 86ºF) . Retain in original package to protect from light.

Source: Bortezomib (Bortezomib) — US FDA prescribing information, 2024-07-22, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.