CV: hypertension, peripheral edema, DEEP VEIN THROMBOSIS, HF, MYOCARDIAL ISCHEMIA/INFARCTION, SUDDEN CARDIAC DEATH.
Endo: hypoglycemia, atrial fibrillation.
F and E: hypercalcemia, hypokalemia, hypomagnesemia, hyponatremia, hypophosphatemia.
GI: anorexia, constipation, diarrhea, HEPATIC FAILURE, hepatotoxicity, nausea.
GU: acute renal failure.
Hemat: anemia, leukopenia, thrombocytopenia, thrombotic thrombocytopenic purpura (TTP)/hemolytic uremic syndrome (hus), lymphopenia.
MS: back pain, chest wall pain, muscle spasms.
Neuro: dizziness, fatigue, headache, hypoesthesia, insomnia, posterior reversible encephalopathy syndrome (pres), weakness, peripheral neuropathy, PROGRESSIVE MULTIFOCAL LEUKOENCEPHALOPATHY (PML).
Resp: cough, dyspnea, ACUTE RESPIRATORY DISTRESS SYNDROME, INTERSTITIAL LUNG DISEASE, PNEUMONITIS, pulmonary edema, PULMONARY EMBOLISM, pulmonary hypertension.
Misc: fever/chills, INFUSION REACTIONS (INCLUDING FACIAL AND LARYNGEAL EDEMA), TUMOR LYSIS SYNDROME.
Combination Therapy with Lenalidomide + Dexamethasone
- IV (Adults): Cycle 1: 20 mg/m2 daily for 2 days (Days 1 and 2); if tolerated, ↑ dose to 27 mg/m2on Days 8, 9, 15, and 16 of a 28-day treatment cycle. Cycles 212: 27 mg/m2 on Days 1, 2, 8, 9, 15, and 16 of a 28-day treatment cycle; Cycles 1318: 27 mg/m2 on Days 1, 2, 15, and 16 of a 28-day treatment cycle. Cycles 19 and subsequent cycles: Continue lenalidomide and dexamethasone (without carfilzomib) until unacceptable toxicity or disease progression.
Combination Therapy with Daratumumab + Dexamethasone or Daratumumab/Hyaluronidase + Dexamethasone
Twice Weekly Regimen- IV (Adults): Cycle 1: 20 mg/m2 daily for 2 days (Days 1 and 2); if tolerated, ↑ dose to 56 mg/m2on Days 8, 9, 15, and 16 of a 28-day treatment cycle. Cycle 2 and subsequent cycles: 56 mg/m2 on Days 1, 2, 8, 9, 15, and 16 of a 28-day treatment cycle. Continue carfilzomib, daratumumab (or daratumumab/hyaluronidase), and dexamethasone until unacceptable toxicity or disease progression.
Once Weekly Regimen- IV (Adults): Cycle 1: 20 mg/m2 on Day 1; if tolerated, ↑ dose to 70 mg/m2on Days 8 and 15 of a 28-day treatment cycle. Cycle 2 and subsequent cycles: 70 mg/m2 on Days 1, 8, and 15 of a 28-day treatment cycle. Continue carfilzomib, daratumumab (or daratumumab/hyaluronidase), and dexamethasone until unacceptable toxicity or disease progression.
Combination Therapy with Isatuximab + Dexamethasone
Twice Weekly Regimen- IV (Adults): Cycle 1: 20 mg/m2 daily for 2 days (Days 1 and 2); if tolerated, ↑ dose to 56 mg/m2on Days 8, 9, 15, and 16 of a 28-day treatment cycle. Cycle 2 and subsequent cycles: 56 mg/m2 on Days 1, 2, 8, 9, 15, and 16 of a 28-day treatment cycle. Continue carfilzomib, isatuximab, and dexamethasone until unacceptable toxicity or disease progression.
Combination Therapy with Dexamethasone
Twice Weekly Regimen- IV (Adults): Cycle 1: 20 mg/m2 daily for 2 days (Days 1 and 2); if tolerated, ↑ dose to 56 mg/m2on Days 8, 9, 15, and 16 of a 28-day treatment cycle. Cycle 2 and subsequent cycles: 56 mg/m2 on Days 1, 2, 8, 9, 15, and 16 of a 28-day treatment cycle. Continue both carfilzomib and dexamethasone until unacceptable toxicity or disease progression.
Once Weekly Regimen- IV (Adults): Cycle 1: 20 mg/m2 on Day 1; if tolerated, ↑ dose to 70 mg/m2on Days 8 and 15 of a 28-day treatment cycle. Cycle 2 and subsequent cycles: 70 mg/m2 on Days 1, 8, and 15 of a 28-day treatment cycle. Continue both carfilzomib and dexamethasone until unacceptable toxicity or disease progression.
Monotherapy
20/27 mg/m2 Regimen- IV (Adults): Cycle 1: 20 mg/m2 daily for 2 days (Days 1 and 2); if tolerated, ↑ dose to 27 mg/m2on Days 8, 9, 15, and 16 of a 28-day treatment cycle. Cycles 212: 27 mg/m2 on Days 1, 2, 8, 9, 15, and 16 of a 28-day treatment cycle; Cycle 13 and subsequent cycles: 27 mg/m2 on Days 1, 2, 15, and 16 of a 28-day treatment cycle. Continue carfilzomib until unacceptable toxicity or disease progression.
20/56 mg/m2 Regimen- IV (Adults): Cycle 1: 20 mg/m2 daily for 2 days (Days 1 and 2); if tolerated, ↑ dose to 56 mg/m2on Days 8, 9, 15, and 16 of a 28-day treatment cycle. Cycles 212: 56 mg/m2 on Days 1, 2, 8, 9, 15, and 16 of a 28-day treatment cycle; Cycle 13 and subsequent cycles: 56 mg/m2 on Days 1, 2, 15, and 16 of a 28-day treatment cycle. Continue carfilzomib until unacceptable toxicity or disease progression.
Renal Impairment
- IV (Adults): Hemodialysis: Administer dose after hemodialysis.
Hepatic Impairment
- IV (Adults): Mild or moderate hepatic impairment: ↓ dose by 25%.
Therapeutic Classification: antineoplastics
Pharmacologic Classification: proteasome inhibitors
Absorption: IV administration results in complete bioavailability.
Distribution: Unknown.
Metabolism/Excretion: Rapidly and extensively metabolized by extrahepatic enzymes. Metabolites have no antineoplastic activity.
Half-life: Unknown.