Kyprolis

Carfilzomib (Carfilzomib) instruction manual

Common name: Carfilzomib
Trade name: Kyprolis
All names: Carfilzomib, Kyprolis, Carfilzomib

Indications:
Kyprolis is a proteasome inhibitor indicated for the treatment of multiple myeloma who have received at least 2 previous treatments (bortezomib and an immunomodulator) and have evidence of disease progression within 60 days of completing the last treatment.

Usage and dosage:
The usage and dosage of this product may vary depending on the dosage form and specifications. Please read the specific drug instructions for use, or follow the doctor's advice.
1. This product should be injected intravenously over 2-10 minutes, continuously for 2 days a week for 3 weeks (i.e., injection on days 1, 2, 89, 15, and 16), then stopped for 12 days, and every 28 days is a course of treatment. In the first course of treatment, the starting dose is 20 mg/m2. If tolerated, the dose can be increased to 27 mg/m2 in the second course of treatment, and this dose can be maintained in subsequent treatments. or until unacceptable toxicity occurs.
2. If toxicity occurs, the dose should be adjusted according to the toxicity level.

Adverse reactions:
The most commonly reported adverse reactions (incidence ≥30%) are fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea and pyrexia.

Taboos:
1. It is not yet clear whether this product can be secreted into breast milk. Breast-feeding women should weigh the consequences of this product and choose to stop taking the drug or stop breastfeeding.
2. The safety and effectiveness of medicines for children have not yet been determined.
3. The safety in patients with grade III or IV heart failure has not yet been determined.

Warnings:
Be alert for the following adverse reactions: cardiac arrest, congestive heart failure, myocardial infarction, pulmonary hypertension, complications of pulmonary tissue, infusion reactions, tumor lysis syndrome, thrombocytopenia, cardiotoxicity and liver failure.

Notes: 1. 0.9% sodium chloride injection or 5% glucose injection should be used to flush the infusion line before and after intravenous infusion of this product.
2. This product can cause infusion reactions, manifested as fever, chills, joint pain, myalgia, facial flushing, facial edema, vomiting, weakness, hypotension, syncope, shortness of breath, angioedema, etc., which can occur immediately after intravenous infusion of this product or within 24 hours after the end of intravenous infusion. Dexamethasone can be taken for prophylaxis before giving this product.
3. This product can cause tumor lysis syndrome, and patients with multiple myeloma and high tumor burden are at greater risk. Patients should be fully hydrated before administering this product and monitor for symptoms of tumor lysis syndrome. If they occur, the drug should be discontinued immediately until symptoms subside.
4. Neutrophil and platelet counts, as well as liver and kidney function should be monitored regularly during treatment.
5. Women of childbearing age should take effective contraceptive measures during treatment.
Storage:

Stored at 2-8℃, protected from light in the original box.

Mechanism of action:

1. 26S proteasome enzyme is a protein complex that can degrade ubiquitin hormone protein. The important role of proteasome enzymes is to regulate the concentration of special proteins in cells to maintain the stability of the intracellular environment. The 26S protease consists of a 20S core part. It consists of two decomposed parts of 19S. The two rings (β rings) of the 20S core size have three active sites (β1, β2 and β5) respectively. These active sites are related to the reduced activity of the three main proteins of the proteasome (post-glutamine depeptide peptide (PGPH), phosphoprotease-like effect and chymotrypsin-like effect respectively). After the protein enters the core part, it is gradually degraded into substitutions containing 3-25 amino acids, and is sequentially reformed by other cellular peptidases.
2. This product is a tetrapeptide epoxypropanone proteasome inhibitor that irreversibly binds to the N-terminal threonine-containing active site of 20S protease. The main target of this product is the chymotrypsin-like (CT-L) subunit that constitutes the proteasome (c205) and immunoprotease (120s). It induces tumor cell death by selectively inhibiting the chymotrypsin-like activity of the proteasome. In in vitro experiments, this product has shown anti-proliferation in solid tumor and hematological tumor cells and animal experiments have shown that this product can inhibit proteasome activity in blood and tissues and delay tumor growth in multiple myeloma, hematological tumor and solid tumor models.

Safety and efficacy: Kyprolis’ new drug trial evaluated 266 patients with relapsed or refractory multiple myeloma who had received at least two prior treatments, including (Velcade) bortezomib and thalidomide. Kyprolis was previously mainly used for colorectal cancer and gastrointestinal stromal tumors. The FDA considers the benefit-risk assessment of Kyprolis (the proposed brand name of carfilzomib) to be beneficial in patients with relapsed or refractory multiple myeloma who have received at least two prior therapies including a protease inhibitor or an immunomodulatory agent (IMiD). Onyx is advancing Kyprolis in multiple lines of treatment in multiple myeloma. The new drug application for Kyprolis is based on the 003-A1 study and supported by other more research data. Study 003-A1 is an open-label, single-arm Phase 2b trial. The trial evaluated 266 patients with relapsed or refractory multiple myeloma who had received at least two prior therapies, including bortezomib (Velcade) and thalidomide.