Carfilzomib

Carfilzomib is a tetrapeptide epoxyketone proteasome inhibitor that irreversibly binds to the N-terminal threonine-containing active sites of the 20S proteasome, the proteolytic core particle within the 26S proteasome. Carfilzomib had antiproliferative and proapoptotic activities in vitro in solid and hematologic tumor cells.

• Kyprolis is a proteasome inhibitor that is indicated: for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy in combination with Lenalidomide and dexamethasone; or Dexamethasone; or Daratumumab and dexamethasone; or Daratumumab and hyaluronidase-fihj and dexamethasone; or Isatuximab and dexamethasone. ( 1 , 14 ) as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.ICD-10: C90.00

• None. None.contraindicated

Hydrate prior to and following Kyprolis as needed. ( 2.1 ) Premedicate prior to all Cycle 1 doses and if infusion-related reactions develop or reappear. ( 2.1 ) The recommended dosing regimens are as follows. See Full Prescribing Information for additional dosage information. ( 2.2 ) Regimen Dosage Infusion Time Kyprolis and Dexamethasone (Kd) or Kyprolis, Daratumumab and Dexamethasone (DKd) or Kyprolis, Daratumumab and hyaluronidase-fihj and Dexamethasone (DKd) 20/70 mg/m 2 once weekly 30 minutes Kyprolis and Dexamethasone (Kd) or Kyprolis, Daratumumab and Dexamethasone (DKd) or Kyprolis, Daratumumab and hyaluronidase-fihj and Dexamethasone (DKd) or Kyprolis, Isatuximab and Dexamethasone (Isa-Kd) or Kyprolis Monotherapy 20/56 mg/m 2 twice weekly 30 minutes Kyprolis, Lenalidomide and Dexamethasone (KRd) or Kyprolis Monotherapy 20/27 mg/m 2 twice weekly 10 minutes 2.1 Administration Precautions Hydration Adequate hydration is required prior to dosing in Cycle 1, especially in patients at high-risk of tumor lysis syndrome (TLS) or renal toxicity. Consider hydration with both oral fluids (30 mL per kg at least 48 hours before Cycle 1, Day 1) and intravenous fluids (250 mL to 500 mL of appropriate intravenous fluid prior to each dose in Cycle 1). If needed, give an additional 250 mL to 500 mL of intravenous fluids following Kyprolis administration. Continue oral and/or intravenous hydration, as needed, in subsequent cycles.

Cardiac Toxicities : Monitor for signs and symptoms of cardiac failure or ischemia. Withhold Kyprolis and evaluate promptly. ( 5.1 ) Acute Renal Failure : Monitor serum creatinine regularly. ( 5.2 ) Tumor Lysis Syndrome (TLS) : Administer pre-treatment hydration. (2.1 ) Monitor for TLS, including uric acid levels and treat promptly. ( 5.3 ) Pulmonary Toxicity, including Acute Respiratory Distress Syndrome, Acute Respiratory Failure, and Acute Diffuse Infiltrative Pulmonary Disease : Withhold Kyprolis and evaluate promptly. ( 5.4 ) Pulmonary Hypertension : Withhold Kyprolis and evaluate. ( 5.5 ) Dyspnea : For severe or life-threatening dyspnea, withhold Kyprolis and evaluate. ( 5.6 ) Hypertension, including Hypertensive Crisis : Monitor blood pressure regularly. If hypertension cannot be controlled, interrupt treatment with Kyprolis. ( 5.7 ) Venous Thrombosis : Thromboprophylaxis is recommended. ( 5.8 ) Infusion-related Reactions : Premedicate with dexamethasone. ( 2.1 , 5.9 ) Hemorrhage : Fatal or serious cases of hemorrhage may occur, including gastrointestinal, pulmonary, and intracranial hemorrhage. Promptly evaluate signs and symptoms of blood loss. ( 5.10 ) Thrombocytopenia : Monitor platelet counts; interrupt or reduce Kyprolis dosing as clinically indicated. ( 2.3 , 5.11 ) Hepatic Toxicity and Hepatic Failure : Monitor liver enzymes regularly. Withhold Kyprolis if suspected. ( 5.12 ) Thrombotic Microangiopathy : Monitor for signs and symptoms. Discontinue Kyprolis if suspected.

The following clinically significant adverse reactions are described elsewhere in the labeling: Cardiac Toxicities [see Warnings and Precautions (5.1) ] Acute Renal Failure [see Warnings and Precautions (5.2) ] Tumor Lysis Syndrome [see Warnings and Precautions (5.3) ] Pulmonary Toxicity [see Warnings and Precautions (5.4) ] Pulmonary Hypertension [see Warnings and Precautions (5.5) ] Dyspnea [see Warnings and Precautions (5.6) ] Hypertension [see Warnings and Precautions (5.7) ] Venous Thrombosis [see Warnings and Precautions (5.8) ] Infusion-Related Reactions [see Warnings and Precautions (5.9) ] Hemorrhage [see Warnings and Precautions (5.10) ] Thrombocytopenia [see Warnings and Precautions (5.11) ] Hepatic Toxicity and Hepatic Failure [see Warnings and Precautions (5.12) ] Thrombotic Microangiopathy [see Warnings and Precautions (5.13) ] Posterior Reversible Encephalopathy Syndrome [see Warnings and Precautions (5.14) ] Progressive Multifocal Leukoencephalopathy [see Warnings and Precautions (5.15) ] The most common adverse reactions occurring in at least 20% of patients treated with Kyprolis in monotherapy trials: anemia, fatigue, thrombocytopenia, nausea, pyrexia, dyspnea, diarrhea, headache, cough, edema peripheral. ( 6 ) The most common adverse reactions occurring in at least 20% of patients treated with Kyprolis in the combination therapy trials: anemia, diarrhea, hypertension, fatigue, upper respiratory tract infection, thrombocytopenia, pyrexia, cough, dyspnea, and insomnia.

Geriatric Use : In the Kyprolis clinical trials, the incidence of adverse reactions was greater in patients ≥ 75 years of age. ( 8.5 ) Hepatic Impairment : Reduce the dose of Kyprolis by 25% in patients with mild or moderate hepatic impairment. ( 2.4 ) Patients on Hemodialysis : Administer Kyprolis after the hemodialysis procedure. ( 2.1 ) Lactation : Advise women not to breastfeed. ( 8.2 ) 8.1 Pregnancy Risk Summary Kyprolis can cause fetal harm based on findings from animal studies and its mechanism of action [see Clinical Pharmacology (12.1) ] . There are no available data on Kyprolis use in pregnant women to evaluate for drug-associated risks. Kyprolis caused embryo-fetal lethality in rabbits at doses lower than the clinical dose (see Data ) . Advise pregnant women of the potential risk to the fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2%–4% and 15%–20%, respectively. Data Animal Data Carfilzomib administered intravenously to pregnant rats and rabbits during the period of organogenesis was not teratogenic at doses up to 2 mg/kg/day in rats and 0.8 mg/kg/day in rabbits.

Metabolism

Carfilzomib at doses between 20 mg/m 2 and 70 mg/m 2 administered as a 30-minute infusion resulted in dose-dependent increases in maximum plasma concentrations (C max ) and area under the curve over time to infinity (AUC 0-INF ) in patients with multiple myeloma. A dose-dependent increase in C max and AUC 0-INF was also observed between carfilzomib 20 mg/m 2 and 56 mg/m 2 as a 2- to 10-minute infusion in patients with relapsed or refractory multiple myeloma.

Acute onset of chills, hypotension, renal insufficiency, thrombocytopenia, and lymphopenia has been reported following a dose of 200 mg of Kyprolis administered in error. There is no known specific antidote for Kyprolis overdosage. In the event of overdose, monitor patients for adverse reactions and provide supportive care as appropriate.

• Jul 20, 2012NDANDA202714Onyx Pharms Amgen

1. 1Plasma Cell Myeloma2,98911%
2. 2Off Label Use2,3598.5%
3. 3Death1,7576.3%
4. 4Fatigue1,5295.5%
5. 5Thrombocytopenia1,5165.5%
6. 6Pneumonia1,3644.9%
7. 7Pyrexia1,1574.2%
8. 8Diarrhoea1,1144.0%
9. 9Dyspnoea1,1134.0%
10. 10Anaemia1,1044.0%
11. 11Neutropenia1,0923.9%
12. 12Nausea1,0633.8%
13. 13Acute Kidney Injury8543.1%
14. 14Drug Ineffective8363.0%
15. 15Asthenia7052.5%

The 10 most recently updated of 272 ClinicalTrials.gov registrations naming Carfilzomib as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• Study Assessing Activity of Intravenous (IV) Etentamig Monotherapy Versus Standard Available Therapies in Adult Participants With Relapsed or Refractory Multiple Myeloma
  Recruiting · Phase 3 · Interventional · 380 enrolled · AbbVie
  NCT06158841updated 2026-06-12
• Phase Ib Study of SAR650984 in Combination With Carfilzomib for Treatment of Relapsed or Refractory Multiple Myeloma
  Completed · Phase 1 · Interventional · 83 enrolled · Thomas Martin, MD
  NCT02332850updated 2026-06-11
• A Study Comparing AZD0120, a Dual-targeted CAR-T Against B-cell Maturation Antigen (BCMA) and CD19, Versus Standard Regimens in Participants With Relapsed Refractory Multiple Myeloma (DURGA-4)
  Recruiting · Phase 3 · Interventional · 508 enrolled · AstraZeneca
  NCT07391657updated 2026-06-11
• Home Treatment With Carfilzomib in Patients With Multiple Myeloma
  Completed · Observational · 9 enrolled · Thomas Lund
  NCT05620238updated 2026-06-10
• A Study to Evaluate the Efficacy and Safety of Belantamab Mafodotin in Combination With Standard of Care in Participants With Relapsed-Refractory Multiple Myeloma (RRMM)
  Recruiting · Phase 2 · Interventional · 200 enrolled · GlaxoSmithKline
  NCT07227311updated 2026-06-10
• Daratumumab, Carfilzomib, Pomalidomide, Dexamethasone In MM
  Active not recruiting · Phase 2 · Interventional · 44 enrolled · Andrew Yee, MD
  NCT04176718updated 2026-06-08
• A Study of an MMSET Inhibitor in Patients With Relapsed and Refractory Multiple Myeloma
  Recruiting · Phase 1 · Interventional · 165 enrolled · K36 Therapeutics, Inc.
  NCT05651932updated 2026-06-08
• MagnetisMM-32: A Study to Learn About the Study Medicine Called Elranatamab in People With Multiple Myeloma (MM) That Has Come Back After Taking Other Treatments (Including Prior Treatment With an Anti-CD38 Antibody and Lenalidomide)
  Recruiting · Phase 3 · Interventional · 492 enrolled · Pfizer
  NCT06152575updated 2026-06-05
• A Study of Daratumumab
  Recruiting · Phase 3 · Interventional · 500 enrolled · Janssen Research & Development, LLC
  NCT05438043updated 2026-06-05
• A Study of Talquetamab With Other Anticancer Therapies in Participants With Multiple Myeloma
  Active not recruiting · Phase 1 · Interventional · 166 enrolled · Janssen Research & Development, LLC
  NCT05050097updated 2026-06-05

Frequently asked questions

How does Carfilzomib work?

Carfilzomib is a tetrapeptide epoxyketone proteasome inhibitor that irreversibly binds to the N-terminal threonine-containing active sites of the 20S proteasome, the proteolytic core particle within the 26S proteasome. Carfilzomib had antiproliferative and proapoptotic activities in vitro in solid and hematologic tumor cells.

What is Carfilzomib used for?

According to FDA labeling, Carfilzomib carries indications including: Kyprolis is a proteasome inhibitor that is indicated: for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy in combination with Lenalidomide and dexamethasone; or Dexamethasone; or Daratumumab and dexamethasone; or Daratumumab and hyaluronidase-fihj and dexamethasone; or Isatuximab and dexamethasone. ( 1 , 14 ) as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Carfilzomib?

Carfilzomib is classified as Proteasome inhibitors, Proteasome Inhibitor, Proteasome Inhibitors, Increased Cellular Death.

What are the brand names for Carfilzomib?

Carfilzomib is marketed under brand names including Kyprolis.

What are the contraindications for Carfilzomib?

Carfilzomib labeling lists contraindications including: None. None.. Always consult the full prescribing information and a clinician.