Kyprolis Carfilzomib for Injection

1. Indications and Usage
Monotherapy:
Indicated for the treatment of adult patients with relapsed or refractory multiple myeloma, who have received one or more prior lines of therapy.
Combination Therapy:
Indicated in combination with:
Lenalidomide and Dexamethasone: For patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy.
Daratumumab and Dexamethasone: For patients with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy.
Dexamethasone: For patients with relapsed or refractory multiple myeloma who have received one or more prior lines of therapy.
2. Dosage and Administration
Route of Administration:
For Intravenous (IV) Infusion ONLY.
Recommended Dosage:
Dose:
Cycle 1: 20 mg/m².
Cycle 2 onwards: 27 mg/m² (if the 20 mg/m² dose is well tolerated).
Schedule: Administer on Days 1, 2, 8, 9, 15, and 16 of each 28-day cycle.
Administration Instructions:
Administer as an IV infusion over 2 to 5 minutes (previously 10 minutes).
Flush the IV line with 0.9% Sodium Chloride Injection before and after administration.
Hydration:
Ensure adequate hydration (e.g., 500 mL to 1000 mL of IV or oral fluids) before administration to reduce the risk of renal toxicity and Tumor Lysis Syndrome (TLS).
3. Mechanism of Action
Proteasome Inhibition:
Carfilzomib is a peptide epoxyketone that selectively and irreversibly binds to the N-terminus of threonine in the active sites of the 20S proteasome.
Induction of Apoptosis:
It primarily inhibits the chymotrypsin-like activity of the 20S proteasome. This inhibition leads to the accumulation of ubiquitinated and misfolded proteins within the cell, triggering the unfolded protein response (UPR) and ultimately inducing apoptosis (programmed cell death) in myeloma cells.
4. Safety and Warnings
Cardiac Toxicity:
Can cause cardiac failure, ischemic events, and cardiopulmonary arrest. Monitor for signs of heart failure (e.g., dyspnea, edema) and ischemia.
Infusion-Related Reactions:
Can occur during or within 24 hours of infusion. Pre-medication with dexamethasone (2 mg–4 mg orally or 4 mg IV) is recommended prior to each dose.
Tumor Lysis Syndrome (TLS):
Rapidly dividing cells may cause TLS. Ensure hydration and monitor electrolytes and uric acid.
Pulmonary Hypertension:
Can cause pulmonary hypertension. Discontinue if suspected.
Embryo-Fetal Toxicity:
Can cause fetal harm. Females of reproductive potential must use effective contraception during treatment and for at least 30 days after the final dose.
5. Adverse Reactions
Most Common (Incidence ≥20%):
Fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea, pyrexia, cough, and headache.
6. Drug Interactions
CYP3A4 Inhibitors/Inducers:
Carfilzomib is not significantly metabolized by CYP450 enzymes; therefore, interactions with CYP3A4 inhibitors or inducers are considered unlikely to be clinically significant.
P-gp Substrate:
Carfilzomib is not a substrate or inhibitor of P-gp.
7. Pharmaceutical Information
Chemical Composition:
Active Ingredient: Carfilzomib.
Appearance: White to off-white lyophilized cake or powder.
Storage: Store vials refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light.