Pronunciation:
car- fil-zoe- mib
Trade Name(s)
Ther. Class.
Pharm. Class.
proteasome inhibitors
Acts as a proteasome inhibitor by binding to sites on the 20s proteasome. Has antiproliferative and proapoptotic activity.
Therapeutic Effect(s):
Delayed progression of multiple myeloma.
Absorption: IV administration results in complete bioavailability.
Distribution: Unknown.
Metabolism and Excretion: Rapidly and extensively metabolized by extrahepatic enzymes. Metabolites have no antineoplastic activity.
Half-life: Unknown.
TIME/ACTION PROFILE (proteasome inhibition)
ROUTE | ONSET | PEAK | DURATION |
---|---|---|---|
IV | within 1 hr | unknown | >48 hr |
Contraindicated in:
Use Cautiously in:
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
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
Drug-Drug
None reported.
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/m2 on Days 8, 9, 15, and 16 of a 28-day treatment cycle. Cycles 2–12: 27 mg/m2 on Days 1, 2, 8, 9, 15, and 16 of a 28-day treatment cycle; Cycles 13–18: 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/m2 on 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/m2 on 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/m2 on 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/m2 on 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/m2 on 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/m2 on Days 8, 9, 15, and 16 of a 28-day treatment cycle. Cycles 2–12: 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/m2 on Days 8, 9, 15, and 16 of a 28-day treatment cycle. Cycles 2–12: 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%.
Lyophilized powder for injection: 10 mg/vial, 30 mg/vial, 60 mg/vial
Monitor for cardiac complications (BP, new or worsening HF, decreased left ventricular function, myocardial ischemia). Hold dose for Grade 3 or 4 cardiac events until recovery. Consider restarting at a reduced dose. If tolerated, may escalate to previous dose.
Monitor for dyspnea frequently during therapy. Interrupt therapy until symptoms resolved; consider restarting with one dose level reduction and increase as tolerated. If drug-induced pulmonary toxicity occurs, discontinue carfilzomib.
Monitor for signs and symptoms of tumor lysis syndrome (hyperuricemia, hyperkalemia, hyperphosphatemia, hypocalcemia) during therapy. Consider uric acid lowering drugs in patients at risk. Manage promptly; may require discontinuation.
Monitor for signs/symptoms of infusion reactions (fever, chills, arthralgia, myalgia, facial flushing, facial edema, laryngeal edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness). May occur immediately or up to 24 hrs after administration. Premedicate with dexamethasone prophylactically.
Assess for signs and symptoms of thrombotic thrombocytopenic purpura /hemolytic uremic syndrome (weakness, confusion or coma, abdominal pain, nausea, vomiting, diarrhea, arrhythmias). Discontinue therapy if symptoms occur.
Monitor for signs and symptoms of PRES (seizure, headache, lethargy, confusion, blindness, altered consciousness, other visual and neurological disturbances, hypertension). Determined with MRI. Discontinue if symptoms occur.
Assess for any new signs or symptoms that may be suggestive of PML, an opportunistic infection of the brain caused by the JC virus, that leads to death or severe disability; withhold dose and notify health care professional promptly. PML symptoms may begin gradually but usually worsen rapidly. Symptoms vary depending on which part of brain is infected (mental function declines rapidly and progressively, causing dementia; speaking becomes increasingly difficult; partial blindness; difficulty walking; rarely, headaches and seizures occur). Diagnosis is usually made via gadolinium-enhanced MRI and CSF analysis. Risk of PML increases with the number of infusions. Hold carfilzomib at first sign of PML.
Lab Test Considerations:
Verify negative pregnancy test before starting therapy.
Monitor CBC and platelet count frequently during therapy. Nadir of thrombocytopenia occurs around Day 8 of 28–day cycle and recovery to baseline by start of next 28–day cycle. If ANC <0.5 x 109 /L, hold dose. If recovered to ≥0.5 x 109 /L, continue at same dose. For subsequent drops to <0.5 x 109 /L, follow recommendations above and consider 1 dose level reduction when restarting carfilzomib. If ANC <0.5 x 109 /L and an oral temperature >38.5°C. or two consecutive readings of >38.0° for more than 2 hrs, hold dose. If ANC returns to baseline and fever resolves, resume therapy at same dose. If platelets <10 x 109 /L or evidence of bleeding with thrombocytopenia, hold dose. If recovered to ≥10 x 109 /L and/or bleeding is controlled, continue at same dose. For subsequent drops to <10 x 109 /L, follow recommendations above and consider 1 dose level reduction when restarting carfilzomib.
Hydrate patient to reduce risk of renal toxicity and tumor lysis syndrome. At least 48 hrs before Cycle 1, Day 1, administer oral fluids (30 mL per kg) and IV fluids (250 mL to 500 mL of IV fluid prior to each dose in Cycle 1). Give an additional 250 mL to 500 mL of IV fluids following administration, if needed. Continue oral and/or IV hydration, as needed, in subsequent cycles. Monitor for fluid overload and adjust hydration to patient needs.
Slowed progression of multiple myeloma.