Kyprolis (carfilzomib)

If grade 3 or 4 new onset or worsening of congestive heart failure, decreased left ventricular function, or myocardial ischemia occurs, carfilzomib therapy should be withheld until the toxicity resolves or returns to baseline. Following resolution, it should be considered whether resuming carfilzomib therapy at a reduced dosage (i.e., a dose of 27 mg/m2 reduced to 20 mg/m2; a dose of 20 mg/m2 reduced to 15 mg/m2) is appropriate based on assessment of potential risks and benefits. If the reduced dosage is tolerated, the dosage may be escalated back to the previous dosage at the discretion of the clinician. (See Cardiac Effects under Cautions: Warnings/Precautions.)

Platelet counts should be monitored frequently during carfilzomib therapy. If grade 3 or 4 neutropenia or grade 4 thrombocytopenia occurs, carfilzomib therapy should be withheld. If full recovery occurs prior to the next scheduled dose, carfilzomib may be resumed at the same dosage level. If the toxicity resolves to grade 2 neutropenia or grade 3 thrombocytopenia, the dosage of carfilzomib may be reduced by one dose level (i.e., a dose of 27 mg/m2 reduced to 20 mg/m2; a dose of 20 mg/m2 reduced to 15 mg/m2). If the reduced dosage is tolerated, the dosage may be escalated back to the previous dosage at the discretion of the clinician. (See Thrombocytopenia under Cautions: Warnings/Precautions.)

In patients who develop grade 3 or 4 elevations of serum aminotransferases (ALT or AST), bilirubin, or other liver abnormalities, carfilzomib therapy should be withheld until the toxicity resolves or returns to baseline. Following resolution, it should be considered whether resuming therapy is appropriate. Therapy may be resumed at a reduced dosage (i.e., a dose of 27 mg/m2 reduced to 20 mg/m2; a dose of 20 mg/m2 reduced to 15 mg/m2) with frequent monitoring of liver function tests. If the reduced dosage is tolerated, the dosage may be escalated back to the previous dosage at the discretion of the clinician. (See Hepatic Toxicity and Hepatic Failure under Cautions: Warnings/Precautions.)

In patients who develop elevated serum creatinine concentrations of 2 or more times the baseline value, carfilzomib therapy should be withheld until renal function recovers to grade 1 or baseline and renal function should be monitored. If nephrotoxicity is attributable to carfilzomib, therapy may then be resumed at a reduced dosage (i.e., a dose of 27 mg/m2 reduced to 20 mg/m2; a dose of 20 mg/m2 reduced to 15 mg/m2). If nephrotoxicity is not attributable to carfilzomib, therapy may be resumed at the dosage used prior to the event. If the reduced dosage is tolerated, the dosage may be escalated back to the previous dosage at the discretion of the clinician.

If other grade 3 or 4 nonhematologic toxicity occurs, carfilzomib therapy should be withheld until the toxicity resolves or returns to baseline. Resumption of therapy at a dosage reduced by one dose level (i.e., a dose of 27 mg/m2 reduced to 20 mg/m2; a dose of 20 mg/m2 reduced to 15 mg/m2) may then be considered. If the reduced dosage is tolerated, the dosage may be escalated back to the previous dosage at the discretion of the clinician.

If grade 3 or 4 peripheral neuropathy occurs, carfilzomib therapy should be withheld until the condition resolves or returns to baseline. Therapy may then be resumed at the dosage used prior to the event or at a reduced dosage (i.e., a dose of 27 mg/m2 reduced to 20 mg/m2; a dose of 20 mg/m2 reduced to 15 mg/m2). If the reduced dosage is tolerated, the dosage may be escalated back to the previous dosage at the discretion of the clinician.

If grade 3 or 4 pulmonary complications (e.g., dyspnea) occur, carfilzomib therapy should be withheld until the toxicity resolves or returns to baseline. Resumption of therapy at a dosage reduced by one dose level (i.e., a dose of 27 mg/m2 reduced to 20 mg/m2; a dose of 20 mg/m2 reduced to 15 mg/m2) may then be considered. If the reduced dosage is tolerated, the dosage may be escalated back to the previous dosage at the discretion of the clinician. (See Pulmonary Complications under Cautions: Warnings/Precautions.)

If pulmonary arterial hypertension (PAH) occurs, carfilzomib therapy should be withheld until the toxicity resolves or returns to baseline. Following resolution, therapy may then be resumed at either the previous dosage or at a dosage reduced by one dose level (i.e., a dose of 27 mg/m2 reduced to 20 mg/m2; a dose of 20 mg/m2 reduced to 15 mg/m2) at the discretion of the clinician. If the reduced dosage is tolerated, the dosage may be escalated back to the previous dosage at the discretion of the clinician. (See Pulmonary Hypertension under Cautions: Warnings/Precautions.)

Carfilzomib is administered IV over 2-10 minutes. The drug should not be administered by rapid IV injection, such as IV push or bolus. Immediately prior to and following carfilzomib administration, the IV administration line should be flushed with 0.9% sodium chloride injection or 5% dextrose injection.

Unreconstituted carfilzomib powder for injection should be stored in unopened vials at 2-8degreesC. Unopened vials should be retained in the original package for protection from light.

Prior to administration, commercially available carfilzomib powder for injection must be reconstituted and the reconstituted solution of the drug may be diluted using proper aseptic technique. The powder is reconstituted by adding 29 mL of sterile water for injection to a vial labeled as containing 60 mg of the drug to provide a solution containing 2-mg/mL. The diluent should be directed toward the inside wall of the vial to minimize foaming. The vial should then be gently swirled and/or inverted for approximately 1 minute, or until complete dissolution of the cake or powder occurs, and inspected visually for particulate matter and discoloration prior to dilution and administration. The resulting solution should not be shaken. If foaming occurs, the solution should be allowed to stand for about 2-5 minutes until foaming subsides. The solution should be clear, colorless, and free of visible particulates.

The desired dose of the carfilzomib reconstituted solution may be given by IV injection or may be further diluted with 5% dextrose injection for IV infusion. The reconstituted solution is diluted by adding an appropriate volume of carfilzomib 2-mg/mL solution to a 50-mL infusion bag containing 5% dextrose injection. Reconstituted and diluted solutions of the drug are stable for up to 4 or 24 hours at room temperature (15-30degreesC) or under refrigeration (2-8degreesC), respectively, regardless of container (e.g., vial, syringe, IV bag).

Carfilzomib should not be admixed with or administered as an infusion with any other drug. Commercially available carfilzomib for injection contains no preservatives and is intended for single use; vials containing the unused portion of the reconstituted solution should be immediately discarded.

No dosing information is available for this tab.

No dosing information is available for this tab.

Carfilzomib appears to be metabolized principally by extrahepatic peptidase cleavage and epoxide hydrolysis. Cytochrome P-450 (CYP)-mediated mechanisms play a minor role in the drug's overall metabolism. In an in vitro study, carfilzomib demonstrated a modest inhibitory effect on CYP3A4/5. The drug does not induce CYP1A2 and CYP3A4 in human hepatocytes in vitro. Carfilzomib is a substrate of P-glycoprotein (P-gp). The drug has shown marginal inhibitory effects on P-gp in a Caco-2 monolayer system.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

The manufacturer states there are no known contraindications to the use of carfilzomib.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

Adverse effects reported in 30% or more of multiple myeloma patients receiving carfilzomib include fatigue, anemia, nausea, dyspnea, diarrhea, and pyrexia. Serious adverse effects occurred in 45% of patients, and included pneumonia, acute renal failure, pyrexia, and congestive heart failure.

Laboratory abnormalities reported in 10% or more of patients receiving carfilzomib include anemia, thrombocytopenia, increased creatinine concentrations, lymphopenia, neutropenia, hypokalemia, hypomagnesemia, leukopenia, increased AST concentrations, hyperglycemia, hypercalcemia, hypophosphatemia, and hyponatremia.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

Safety and efficacy of carfilzomib have not been established in pediatric patients.

Category D. (See Users Guide and see Fetal/Neonatal Morbidity and Mortality under Cautions: Warnings/Precautions.)

It is not known whether carfilzomib is distributed into human milk. Because many drugs are distributed into human milk and because of the potential for serious adverse reactions to carfilzomib in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

In a population pharmacokinetic analysis, carfilzomib exposure in patients 65 years of age and older did not differ substantially from that in adult patients younger than 65 years of age following a single 20-mg/m2 IV dose of the drug. In clinical studies, no clinically important differences in safety or efficacy were observed between patients 65 years of age and older and younger adults. (See Dosage and Administration: Special Populations.)