Carfilzomib
Carfilzomib Uses, Dosage, Side Effects, Food Interaction and all others data.
Carfilzomib is an injectable antineoplastic agent (IV only). Chemically, it is a modified tetrapeptidyl epoxide and an analog of epoxomicin. It is also a selective proteasome inhibitor. FDA approved on July 20, 2012.
Intravenous carfilzomib administration resulted in suppression of proteasome chymotrypsin-like activity when measured in blood 1 hour after the first dose. On Day 1 of Cycle 1, proteasome inhibition in peripheral blood mononuclear cells (PBMCs) ranged from 79% to 89% at 15 mg/m2, and from 82% to 83% at 20 mg/m2. In addition, carfilzomib administration resulted in inhibition of the LMP2 and MECL1 subunits of the immunoproteasome ranging from 26% to 32% and 41% to 49%, respectively, at 20 mg/m2. Proteasome inhibition was maintained for ≥ 48 hours following the first dose of carfilzomib for each week of dosing. Resistance against carfilzomib has been observed and although the mechanism has not been confirmed, it is thought that up-regulation of P-glycoprotein may be a contributing factor. Furthermore, studies suggest that carfilzomib is more potent than bortezomib.
| Trade Name | Carfilzomib |
| Availability | Prescription only |
| Generic | Carfilzomib |
| Carfilzomib Other Names | Carfilzomib |
| Related Drugs | Kyprolis, Revlimid, Velcade, Darzalex, Pomalyst, Ninlaro |
| Weight | 10mg, 30mg, 60mg, |
| Type | Intravenous Powder For Injection, Intravenous |
| Formula | C40H57N5O7 |
| Weight | Average: 719.9099 Monoisotopic: 719.425799203 |
| Protein binding | Over the concentration range of 0.4 - 4 micromolar, carfilzomib was 97% protein bound. |
| Groups | Approved, Investigational |
| Therapeutic Class | |
| Manufacturer | |
| Available Country | United States |
| Last Updated: | September 19, 2023 at 7:00 am |
Uses
Carfilzomib is a proteasome inhibitor used either alone or in conjunction with a chemotherapy regimen to treat patients with relapsed or refractory multiple myeloma.
Carfilzomib is indicated for the treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an immunomodulatory agent and have demonstrated disease progression on or within 60 days of completion of the last therapy. Approval is based on response rate.
Carfilzomib is also used to associated treatment for these conditions: Refractory Multiple Myeloma, Waldenström's Macroglobulinemia (WM)
How Carfilzomib works
Carfilzomib is made up of four modified peptides and acts as a proteasome inhibitor. Carfilzomib irreversibly and selectively binds to N-terminal threonine-containing active sites of the 20S proteasome, the proteolytic core particle within the 26S proteasome. This 20S core has 3 catalytic active sites: the chymotrypsin, trypsin, and caspase-like sites. Inhibition of the chymotrypsin-like site by carfilzomib (β5 and β5i subunits) is the most effective target in decreasing cellular proliferation, ultimately resulting in cell cycle arrest and apoptosis of cancerous cells. At higher doses, carfilzomib will inhibit the trypsin-and capase-like sites.
Toxicity
Most commonly reported adverse reactions (incidence ≥ 30%) are fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea, and pyrexia. The two dose limiting toxicities are thrombocytopenia and febrile neutropenia. Maximum tolerate dose = 15 mg/m^2
Food Interaction
No interactions found.Carfilzomib Hypertension interaction
[Moderate] The use of carfilzomib has been associated with hypertension, including hypertensive crisis and hypertensive emergency.
It is recommended to monitor blood pressure regularly in all patients, especially in hypertensive patients.
Care should be taken and if hypertension cannot be adequately controlled, withhold therapy and consider whether to restart therapy based on a benefit
Carfilzomib Drug Interaction
Moderate: pomalidomideUnknown: lorazepam, loratadine, sulfamethoxazole / trimethoprim, ubiquinone, prochlorperazine, copper gluconate, dexamethasone, dexamethasone, omega-3 polyunsaturated fatty acids, glycerin, metoprolol, bioflavonoids, lenalidomide, acetaminophen, cyanocobalamin, cholecalciferol, ondansetron, zoledronic acid, cetirizine
Carfilzomib Disease Interaction
Major: TLSModerate: cardiac disease, dyspnea, hemorrhage, hepatic toxicity, hypertension, PRES, pulmonary hypertension, pulmonary toxicity, renal failure, TTP/HUS, venous thrombosis
Volume of Distribution
Vd, steady state, 20 mg/m^2 = 28 L
Elimination Route
Cmax, single IV dose of 27 mg/m^2 = 4232 ng/mL; AUC, single IV dose of 27 mg/m^2 = 379 ng•hr/mL; Carfilzomib does not accumulation in the systemic. At doses between 20 and 36 mg/m2, there was a dose-dependent increase in exposure.
Half Life
Following intravenous administration of doses ≥ 15 mg/m^2, carfilzomib was rapidly cleared from the systemic circulation with a half-life of ≤ 1 hour on Day 1 of Cycle 1.
Clearance
Systemic clearance = 151 - 263 L/hour. As this value exceeds hepatic blood flow, it suggests that carfilozmib is cleared extrahepatically.
Innovators Monograph
You find simplified version here Carfilzomib
