Generic Name and Formulations:
Carfilzomib 10mg, 30mg, 60mg; per vial; lyophilized pwd for IV infusion after reconstitution; preservative-free.
Indications for KYPROLIS:
In combination with dexamethasone or lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received 1–3 lines of therapy. As a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received ≥1 lines of therapy.
See full labeling. Hydrate prior to and following administration as needed. Premedicate with dexamethasone prior to all Cycle 1 doses, during subsequent cycles, and if infusion reactions occur. Dexamethasone combination: infuse over 30mins. Once weekly regimen: give once weekly for 3 weeks (Days 1, 8, 15), followed by a 13-day rest period (Days 16–28). In Cycle 1: initially 20mg/m2 per dose on Day 1; if tolerated increase to 70mg/m2 on Day 8 and subsequent cycles. Twice weekly regimen: give on two consecutive days each week for 3 weeks (Days 1, 2, 8, 9, 15, and 16), followed by a 12-day rest period (Days 17–28). In Cycle 1: initially 20mg/m2 per dose on Days 1 and 2; if tolerated increase to 56mg/m2 on Day 8 and subsequent cycles. Lenalidomide/dexamethasone combination: infuse over 10mins on two consecutive days each week for 3 weeks (Days 1, 2, 8, 9, 15, and 16), followed by a 12-day rest period (Days 17–28). In Cycle 1: initially 20mg/m2 per dose on Days 1 and 2; if tolerated increase to 27mg/m2 on Day 8 and subsequent cycles. From Cycle 13, omit the Day 8 and 9 doses. Discontinue carfilzomib after Cycle 18. See full labeling for lenalidomide and dexamethasone dosing. Monotherapy: give on two consecutive days each week for 3 weeks (Days 1, 2, 8, 9, 15, and 16), followed by a 12-day rest period (Days 17–28). In Cycle 1: initially 20mg/m2 per dose on Days 1 and 2; if tolerated increase to 27mg/m2 on Day 8 (by 10-min infusion regimen) or 56mg/m2 on Day 8 (by 30-min infusion regimen) and continue same dose for subsequent cycles. From Cycle 13, omit the Day 8 and 9 doses. All: continue until disease progression or unacceptable toxicity occurs. Mild or moderate hepatic impairment: reduce dose by 25%. ESRD on dialysis: give dose after session. Dose modifications for toxicity: see full labeling.
Monitor for signs/symptoms of cardiac failure or ischemia; evaluate promptly if toxicity is suspected. Increased risk of cardiac complications in patients with NYHA Class III and IV heart failure, recent MI, conduction abnormalities, angina, uncontrolled arrhythmias; do full medical assessment prior to starting. Pulmonary hypertension; if suspected, withhold therapy until resolved; may consider restarting after reevaluation. Discontinue if pulmonary toxicity occurs. Monitor for tumor lysis syndrome (TLS); interrupt therapy and manage promptly if occurs. Interrupt for Grade 3 or 4 dyspnea until resolved; consider restarting after reevaluation. Maintain adequate hydration. Monitor for volume overload. Evaluate signs/symptoms of blood loss; reduce or withhold dose as appropriate. Monitor for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS); discontinue and evaluate if suspected. Discontinue and evaluate if posterior reversible encephalopathy syndrome (PRES) is suspected. Control BP prior to initiation; withhold and evaluate if uncontrolled. Monitor BP, platelets, renal function, liver enzymes, electrolytes (eg, potassium) regularly; reduce or withhold dose as needed. Hepatic impairment. Give thromboprophylaxis for combination therapy. Consider antiviral prophylaxis to prevent herpes zoster reactivation. Elderly (≥75yrs). Embryo-fetal toxicity. Use effective contraception during and for ≥6 months (females) or ≥3 months (males w. female partners) after last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 2 weeks after last dose).
Increased risk of thrombosis with oral or hormonal contraceptives; consider alternatives during combination therapy. Increased fatal/serious toxicities in combination with melphalan + prednisone in newly diagnosed transplant-ineligible patients.
Anemia, neutropenia, diarrhea, dyspnea, fatigue, thrombocytopenia, pyrexia, insomnia, muscle spasm, cough, upper RTI, hypokalemia, nausea, headache, peripheral edema; cardiotoxicity, pulmonary HTN, acute renal failure (may be fatal), infusion reactions, hemorrhage, TLS, hepatic toxicity/failure, TTP/HUS, PRES.