Carfilzomib: Anti-cancer medication

Carfilzomib is an anti-cancer drug sold under the trade name Kyprolis. It acts as a selective proteasome inhibitor(drugs that block the action of proteasomes, cellular complexes that break down proteins). It has a chemical analog of epoxomicin. Chemically, it is a tetrapeptide epoxyketone. It is recommended by Clinicians for the patient of  multiple myeloma, a type of cancer of plasma cells that is a type of white blood cell that produces antibodies.

Usage of carfilzomib Injection

Carfilzomib Injection is used to treat adult patients with relapsed or refractory multiple myeloma who have received one or three lines of therapy, including lenalidomide and dexamethasone or dexamethasone or daratumumab and dexamethasone in fixed ratios.
Sometimes, in addition to dexamethasone and lenalidomide, other drugs are also used with carfilzomib to help treat multiple myeloma. These drugs are:

• cyclophosphamide
• panobinostat
• pomalidomide

Dosage of carfilzomib

Carfilzomib dosage depends upon several factors, and treatment will be according to the prescription which the doctor will prescribe to the patient. Generally, doctors start with the low dosage and adjust it with time to reach the proper dosage for the patient.
Carfilzomib comes as a powder inside single-dose vials. It is mixed with liquid and given to the patient as an intravenous infusion by the doctor. With the intravenous injection, the drug is injected into your vein over some time. In general, dosing is based on a 4-week treatment cycle. It is given once or twice each week for 3 weeks, followed by 1 week without it. The number of treatment cycles that a doctor recommends will depend on the patient’s situation. Typically, carfilzomib is given either until your disease gets worse or you have side effects that are too severe.

Carfilzomib comes in the strength of 60 mg.

Overdosage

There is no antidote for overdose of Carfilzomib. If there is an overdose of Carfilzomib drug, acute onset of chills, hypertension, renal insufficiency, thrombocytopenia and lymphopenia has been reported.

Side effects of carfilzomib drugs

Most Common Side Effects

• Anemia (low red blood cell level)
• Thrombocytopenia (low platelet level)
• Nausea
• Diarrhea
• Trouble breathing
• Cough
• Tiredness
• Fever
• Headache
• Trouble falling asleep or staying asleep
• Edema (swelling) in some body parts

Severe Side Effects

Severe side effects are not common, but they may occur. These side effects are as follows:

• Severe allergic reaction
• Heart problems, such as heart attack or heart failure:
  Death due to cardiac arrest has been observed within one day of Kyprolis administration in some patients. Cardiac failure is observed more in old aged people rather than young people. Therefore, adequate hydration is required before each dose in cycle 1, monitoring patient’s evidence of volume overload, especially patients at risk for cardiac failure.
• Serious infections, such as:
  Acute renal failure: Acute renal failure has occurred in approximately 9% of patients who received carfilzomib. It is frequent in patients with advanced relapsed and multiple refractory monotherapies and proved fatal in some cases.
• Tumor lysis syndrome (imbalance in your body that is caused by cancer cell death): Cases of tumor lysis syndrome, including fatal outcomes, have been reported in patients who received carfilzomib 60 mg Injection. Patients with multiple myeloma and a high tumor burden are considered at increased risk for tumor lysis syndrome.
• Acute respiratory failure: Acute respiratory failure is observed in 2% of patients after kyprolis administration.In addition, diseases such as pneumonitis and interstitial lung occurred in approximately 2% of patients.
• Hypertension (high blood pressure)
• Venous thromboembolism
• Bleeding problems, which may be caused by severe thrombocytopenia (very low platelet level)
• Liver problems, such as elevated liver enzymes (enzymes are certain types of proteins)
• Thrombotic microangiopathy (blood clots in your small blood vessels)
• Posterior reversible encephalopathy syndrome (swelling in your brain)

Preparation and Administration

Kyprolis vials contain no antimicrobial preservatives and are aimed for single-dose only. The remade solution contains carfilzomib at a concentration of 2 mg/mL.
Preparation Steps are as follows:

• Remove the vial from the refrigerator just before to use.
• Now calculate the dose and number of vials of Kyprolis required using the patient’s BSA at baseline.
• Aseptically reconstitute each Kyprolis vial only with Sterile Water for Injection, USP(use in specific populations) using the volumes. Use a 21-gauge or larger needle to reconstitute each vial by slowly injecting Sterile Water for Injection, USP through the stopper and directing the Sterile Water for Injection, USP onto the inside wall of the vial to minimize foaming.
• Slowly invert the vial for one minute, or until complete dissolution. If foaming occurs, allow the solution to settle in the vial until foaming subsidies for approx. 5 minutes and the solution is clear.
• Inspect for particulate matter and discoloration before administering. The reconstituted product needs to be a clear, colorless solution and should not be administered if any discoloration or particulate matter is observed.
• Discard any unused portion left in the vial. Do not pool unused portions from the vials. One should not administer more than one dose from a vial.
• Administer Kyprolis directly by intravenous infusion or in a 50 mL to 100 mL intravenous bag containing 5% dextrose Injection, USP. Do not administer as an intravenous push.
• When administering in an intravenous bag, use a 21-gauge or larger gauge needle to withdraw the calculated dose from the vial and dilute it into a 50 mL or 100 mL intravenous bag containing only 5% Dextrose Injection, USP.
• Flush the intravenous administration line with normal saline or 5% Dextrose Injection, USP immediately before and after Kyprolis administration.
• Do not mix Kyprolis with or administer as an infusion with other medicinal products.

Warnings and Precautions

• Cardiac toxicities may occur if there are pre-existing cardiac failures, for example: congestive heart failure, pulmonary edema, decreased ejection fraction. To avoid cardiac toxicity patients should be examined for clinical signs and symptoms for cardiac ischemia or cardiac failure.
• Cases of acute renal failure are observed in 9% of patients after receiving carfilzomib Injection. In some cases such events are fatal too. So, before administering carfilzomib, as a precaution, monitor renal functioning of the patient with regular measurement of the serum creatinine or estimated creatinine clearance.
• In case of tumor lysis syndrome(tls), severe and fatal outcomes have been observed after receiving carfilzomib. Patients with multiple myeloma and a high tumor burden are at high risk of tls. As a precautionary measure, administer oral and intravenous fluids before administration of Carfilzomib in Cycle 1 and in following cycles as needed. Consider uric acid-lowering drugs in patients at risk for TLS.
• Based on the research and findings in animals, Carfilzomib can cause fetal harm when given to a pregnant woman.Therefore, it is advised to females of reproductive potential to use effective contraception during treatment with Carfilzomib and for six months following the final dose.