Bortezomib is a proteasome inhibitor firstapproved by the FDA in 2003 for the treatment of multiple myeloma and certain types of mantle cell lymphoma. It works by blocking the proteasome, a cellular complex responsible for breaking down proteins, which leads to the accumulation of defective proteins and triggers cancer cell death. Administered via intravenous or subcutaneous injection, Bortezomib is often used in combination with other chemotherapeutic agents to improve treatment outcomes and extend patient survival.
BRAND NAMES
Velcade® – the original and most widely known brand
Bortecad® – generic/alternative brand in some regions
Boromax® – available in select markets
MECHANISM OF ACTION
Bortezomib is a proteasomeinhibitor that blocks the 26S proteasome, preventing the breakdown of defective proteins. This leads to protein accumulation, triggers cell stress, and a ctivates apoptosis, resulting in cancer cell death, particularly in multiple myeloma cells.
PHARMACOKINETICS
Absorption
Bortezomib is given by intravenousor subcutaneous injection. After subcutaneous injection, it is rapidly absorbed, reaching peak levels in about 30 minutes, with a bioavailability of around 80%.
Distribution
Bortezomib is widely distributed in the body and is approximately 83% bound to plasma proteins. It has a large volume of distribution, allowing it to reach various tissues, which is important for its effectiveness against multiple myelomacells.
Metabolism
Bortezomib is primarily metabolized in the liver by cytochrome P450 enzymes, mainly CYP3A4, CYP2C19, and CYP1A2. Its metabolism produces inactive metabolites, which are then eliminated, allowing the drug to exert its proteasome-inhibiting effects while minimizing accumulation in the body.
Excretion
Bortezomib is primarily excreted through the feces (about 60%) and to a lesser extent via urine (about 30%). Most of the drug is eliminated as metabolites, with less than 10% excreted unchanged, reflecting extensive hepatic metabolism before elimination.
PHARMACODYNAMICS
Bortezomib is a proteasome inhibitor that blocks the 26S proteasome, causing protein accumulation, cell stress, and activation of apoptosis, leading to cancer cell death, especially in multiple myeloma and mantle cell lymphoma.
ADMINISTRATION
Bortezomib is given by intravenous or subcutaneous injection, often in cycles. The subcutaneous route is preferred for lower risk of neuropathy, and it is frequently used with other chemotherapy drugs to treat multiple myeloma and mantle cell lymphoma.
DOSAGE AND STRENGTH
Bortezomib is usually given at 1.3 mg/m² via IV or SC injection, twice weeklyfor two weeks in a 21-day cycle. It comes in 3.5 mg vials, and doses may be adjusted based on toleranceor side effects.
FOOD INTERACTIONS
Bortezomib can be taken with or without food, but patients should avoid grapefruit or grapefruit juice, which may affect CYP3A4 metabolism and alter drug levels.
DRUG INTERACTIONS
Bortezomib can interact with drugs that affect CYP3A4, CYP2C19, or CYP1A2 enzymes, such as ketoconazole, rifampin, and phenytoin, which may alter its metabolism. Combining Bortezomib with other myelosuppressive or neurotoxic drugs can increase the risk of blood cell suppression or nerve damage, so careful monitoring is required.
CONTRAINDICATIONS
Bortezomib is contraindicated in patients with hypersensitivity to the drug or boron. Caution is needed in those with peripheral neuropathy, severe liver problems, active infections, or during pregnancy and lactation.
SIDE EFFECTS
Fatigue
Nausea
Diarrhea
Constipation
Peripheral neuropathy
Low blood counts
Heart problems
Severe infections
Liver toxicity
Allergic reactions
TOXICITY
Bortezomib can cause peripheral neuropathy, low blood counts, liver toxicity, and sometimes heart problems. Careful monitoring helps reduce serious adverse effects.
