Version July 2025
Dosage guidance:
Safety: Adequate hydration with oral fluids (30 mL/kg at least 48 hours prior to cycle 1, day 1) and IV fluids (250 to 500 mL of appropriate solution before each dose in cycle 1) is necessary prior to cycle 1, particularly in patients at risk for tumor lysis syndrome or renal toxicity. If needed, administer an additional 250 to 500 mL of appropriate IV fluid after carfilzomib administration; continue oral and/or IV hydration in subsequent cycles if necessary. Adjust hydration based on individual needs. Premedication may be required to reduce the incidence and severity of infusion reactions (Ref).
Dosing: Calculate carfilzomib dose using actual BSA. Patients with a BSA >2.2 m2 should be dosed using a BSA of 2.2 m2. Dose adjustments for weight changes of ≤20% are not necessary (Ref).
Clinical considerations: Consider antiviral prophylaxis to decrease the risk of herpes zoster reactivation. Provide thromboprophylaxis when administering in combination with other therapies per institutional and clinical practice guidelines based on underlying risk factors. Control/optimize hypertension prior to initiating carfilzomib (Ref).
Heart transplantation, desensitization (adjunctive) (off-label use): Note: Optimal dose, frequency, and duration of therapy have not been established and vary based on institutional protocols. Administer as part of an appropriate combination regimen. An example regimen is provided.
IV: 20 mg/m2 for 6 doses administered on days 1, 2, 8, 9, 15, and 16; cycle may be repeated until clinical endpoints achieved (Ref). Escalating doses up to 36 mg/m2/dose were used in a single case after inadequate response to the initial cycle (Ref).
Kidney transplantation, desensitization (adjunctive) (off-label use): Note: Optimal dose, frequency, and duration of therapy have not been established and vary based on institutional protocols. Administer as part of an appropriate combination regimen. An example regimen is provided.
IV: 20 mg/m2/day on days 1 and 2; then 27 mg/m2/day on days 8, 9, 15, and 16; then 36 mg/m2/day on days 29, 30, 36, 37, 43, and 44 (total of 12 doses) (Ref).
Lung transplantation, antibody-mediated rejection, treatment (adjunctive) (off-label use): Note: Optimal dose, frequency, and duration of therapy have not been established and vary based on institutional protocols. Administer as part of an appropriate combination regimen. An example regimen is provided.
IV: 20 mg/m2 administered over 10 to 30 minutes for 6 doses administered on days 1, 2, 8, 9, 15, and 16 (Ref).
Multiple myeloma, newly diagnosed (off-label use):
Note: Consider antihyperuricemic agents in patients at risk for tumor lysis syndrome. Premedicate with dexamethasone orally or IV at least 30 minutes to 4 hours prior to all doses in cycle 1 to reduce the incidence and severity of infusion reactions; resume dexamethasone premedication if symptoms occur in subsequent cycles. When using carfilzomib in combination, premedicate with the recommended dexamethasone dose defined as part of the combination therapy (refer to protocol). If carfilzomib is administered as a single agent, premedicate with dexamethasone 4 mg (10-minute infusion) or 8 mg (30-minute infusion) orally or IV in cycle 1 and as needed thereafter to minimize infusion-related reactions (Ref).
Multiple myeloma, newly diagnosed, in combination with cyclophosphamide and dexamethasone; 20/36 mg/m2 twice-weekly regimen (adults ≥65 years or ineligible for autologous transplant):
Cycle 1: IV: 20 mg/m2 over 30 minutes on days 1 and 2, and 36 mg/m2 over 30 minutes on days 8, 9, 15, and 16 of a 28-day treatment cycle (in combination with cyclophosphamide and dexamethasone) (Ref).
Cycles 2 to 9: IV: 36 mg/m2 over 30 minutes on days 1, 2, 8, 9, 15, and 16 of a 28-day treatment cycle (in combination with cyclophosphamide and dexamethasone) (Ref).
Cycles 10 and beyond (maintenance): IV: 36 mg/m2 on days 1, 2, 15, and 16 of a 28-day treatment cycle (as a single-agent) until disease progression or unacceptable toxicity (Ref).
Multiple myeloma, newly diagnosed, in combination with lenalidomide, daratumumab, and dexamethasone; 20/56 mg/m2 once-weekly regimen (in the absence of autologous transplant):
Cycle 1: IV: 20 mg/m2 over 30 minutes on day 2, and 56 mg/m2 over 30 minutes on days 8 and 15 of a 28-day treatment cycle (in combination with lenalidomide, dexamethasone, and daratumumab) (Ref).
Cycles 2 to 8: IV: 56 mg/m2 over 30 minutes on days 1, 8, and 15 of a 28-day treatment cycle (in combination with lenalidomide, dexamethasone, and daratumumab) (Ref).
Multiple myeloma, relapsed or refractory:
Note: Consider antihyperuricemic agents in patients at risk for tumor lysis syndrome. Premedicate with dexamethasone orally or IV at least 30 minutes to 4 hours prior to all doses in cycle 1 to reduce the incidence and severity of infusion reactions; resume dexamethasone premedication if symptoms occur in subsequent cycles. When using carfilzomib in combination, premedicate with the recommended dexamethasone dose defined as part of the combination therapy (refer to protocol). If carfilzomib is administered as a single agent, premedicate with dexamethasone 4 mg (10-minute infusion) or 8 mg (30-minute infusion) orally or IV in cycle 1 and as needed thereafter to minimize infusion-related reactions (Ref).
Multiple myeloma, relapsed or refractory, single-agent; 20/27 mg/m2 twice-weekly regimen:
Cycle 1: IV: 20 mg/m2 over 10 minutes on days 1 and 2; if tolerated, increase dose to 27 mg/m2 over 10 minutes on days 8, 9, 15, and 16 of a 28-day treatment cycle.
Cycles 2 to 12: IV: 27 mg/m2 over 10 minutes on days 1, 2, 8, 9, 15, and 16 of a 28-day treatment cycle.
Cycle 13 and beyond: IV: 27 mg/m2 over 10 minutes on days 1, 2, 15, and 16 of a 28-day treatment cycle; continue until disease progression or unacceptable toxicity.
Note: In a randomized study, 12 cycles of the 20/27 mg/m2 regimen were compared to the 20/56 mg/m2 regimen (both administered in combination with dexamethasone); while there was no significant difference in response rates or progression-free survival, the 20/27 mg/m2 regimen was associated with a statistically significantly lower incidence of peripheral neuropathy, thrombocytopenia, and fatigue (Ref).
Multiple myeloma, relapsed or refractory, single-agent; 20/56 mg/m2 twice-weekly regimen:
Cycle 1: IV: 20 mg/m2 over 30 minutes on days 1 and 2; if tolerated, increase dose to 56 mg/m2 over 30 minutes on days 8, 9, 15, and 16 of a 28-day treatment cycle.
Cycles 2 to 12: IV: 56 mg/m2 over 30 minutes on days 1, 2, 8, 9, 15, and 16 of a 28-day treatment cycle.
Cycle 13 and beyond: IV: 56 mg/m2 over 30 minutes on days 1, 2, 15, and 16 of a 28-day treatment cycle; continue until disease progression or unacceptable toxicity.
Multiple myeloma, relapsed or refractory, in combination with lenalidomide and dexamethasone; 20/27 mg/m2 twice-weekly regimen (KRd regimen):
Cycle 1: IV: 20 mg/m2 over 10 minutes on days 1 and 2; if tolerated, increase dose to 27 mg/m2 over 10 minutes on days 8, 9, 15, and 16 of a 28-day treatment cycle (Ref).
Cycles 2 to 12: IV: 27 mg/m2 over 10 minutes on days 1, 2, 8, 9, 15, and 16 of a 28-day treatment cycle (Ref).
Cycles 13 to 18: IV: 27 mg/m2 over 10 minutes on days 1, 2, 15, and 16 of a 28-day treatment cycle; discontinue carfilzomib after cycle 18; beginning with cycle 19, lenalidomide and dexamethasone may be continued until disease progression or unacceptable toxicity (Ref).
Multiple myeloma, relapsed or refractory, in combination with dexamethasone; 20/56 mg/m2 twice-weekly regimen:
Cycle 1: IV: 20 mg/m2 over 30 minutes on days 1 and 2; if tolerated, increase dose to 56 mg/m2 over 30 minutes on days 8, 9, 15, and 16 of a 28-day treatment cycle (Ref).
Cycle 2 and beyond: IV: 56 mg/m2 over 30 minutes on days 1, 2, 8, 9, 15, and 16 of a 28-day treatment cycle; continue until disease progression or unacceptable toxicity (Ref).
Multiple myeloma, relapsed or refractory, in combination with dexamethasone; 20/70 mg/m2 once-weekly regimen:
Cycle 1: IV: 20 mg/m2 over 30 minutes on day 1; increase dose to 70 mg/m2 over 30 minutes on days 8 and 15 of a 28-day treatment cycle (Ref).
Cycle 2 and beyond: IV: 70 mg/m2 over 30 minutes on days 1, 8, and 15 of a 28-day treatment cycle; continue until disease progression or unacceptable toxicity (Ref).
Multiple myeloma, relapsed or refractory, in combination with daratumumab and dexamethasone or daratumumab/hyaluronidase and dexamethasone; 20/56 mg/m2 twice-weekly regimen (DKd regimen):
Cycle 1: IV: 20 mg/m2 over 30 minutes on days 1 and 2; if tolerated, increase dose to 56 mg/m2 over 30 minutes on days 8, 9, 15, and 16 of a 28-day treatment cycle (Ref).
Cycles 2 and beyond: IV: 56 mg/m2 over 30 minutes on days 1, 2, 8, 9, 15, and 16 of a 28-day treatment cycle; continue until disease progression or unacceptable toxicity (Ref).
Multiple myeloma, relapsed or refractory, in combination with daratumumab and dexamethasone or daratumumab/hyaluronidase and dexamethasone; 20/70 mg/m2 once-weekly regimen (DKd regimen):
Cycle 1: IV: 20 mg/m2 over 30 minutes on day 1; if tolerated, increase dose to 70 mg/m2 over 30 minutes on days 8 and 15 of a 28-day treatment cycle (Ref).
Cycles 2 and beyond: IV: 70 mg/m2 over 30 minutes on days 1, 8, and 15 of a 28-day treatment cycle; continue until disease progression or unacceptable toxicity (Ref).
Multiple myeloma, relapsed or refractory, in combination with isatuximab and dexamethasone; 20/56 mg/m2 twice-weekly regimen (IsaKd regimen):
Cycle 1: IV: 20 mg/m2 over 30 minutes on days 1 and 2; if tolerated, increase dose to 56 mg/m2 over 30 minutes on days 8, 9, 15, and 16 of a 28-day treatment cycle (Ref).
Cycles 2 and beyond: IV: 56 mg/m2 over 30 minutes on days 1, 2, 8, 9, 15, and 16 of a 28-day treatment cycle; continue until disease progression or unacceptable toxicity (Ref).
Multiple myeloma, relapsed or refractory, in combination with pomalidomide and dexamethasone (off-label combination); 20/27 mg/m2 once-weekly regimen (KPd regimen):
Cycle 1: IV: 20 mg/m2 over 10 minutes on day 1; if tolerated, increase dose to 27 mg/m2 over 10 minutes on days 8 and 15 of a 28-day treatment cycle (Ref).
Cycles 2 to 8: IV: 27 mg/m2 over 10 minutes on days 1, 8, and 15 of a 28-day treatment cycle (Ref).
Cycles 9 and beyond (maintenance): IV: 27 mg/m2 over 10 minutes on days 1, 8, and 15 of a 28-day treatment cycle; continue until disease progression or unacceptable toxicity (Ref). Refer to protocol for further information.
Multiple myeloma, relapsed or refractory, in combination with pomalidomide and dexamethasone (off-label combination); 20/27 mg/m2 twice-weekly regimen (KPd regimen):
Cycle 1: IV: 20 mg/m2 over 30 minutes on days 1 and 2; if tolerated, increase dose to 27 mg/m2 over 30 minutes on days 8, 9, 15, and 16 of a 28-day treatment cycle (Ref).
Cycles 2 to 6: IV: 27 mg/m2 over 30 minutes on days 1, 2, 8, 9, 15, and 16 of a 28-day treatment cycle (Ref).
Cycles 7 and beyond (maintenance): IV: 27 mg/m2 over 30 minutes on days 1, 2, 15, and 16 of a 28-day treatment cycle; continue until disease progression or unacceptable toxicity (Ref). Refer to protocol for further information.
Waldenström macroglobulinemia (CaRD regimen) (off-label use):
Note: Consider antihyperuricemic agents in patients at risk for tumor lysis syndrome. When using carfilzomib in combination, premedicate with the recommended dexamethasone dose defined as part of the combination therapy (refer to protocol).
Induction:
Cycle 1: IV: 20 mg/m2 over 20 minutes on days 1, 2, 8, and 9 of a 21-day treatment cycle (in combination with dexamethasone and rituximab) (Ref).
Cycles 2 to 6: IV: 36 mg/m2 over 30 minutes on days 1, 2, 8, and 9 of a 21-day treatment cycle (in combination with dexamethasone and rituximab) (Ref).
Maintenance (started 8 weeks after completion of induction therapy in patients with stable disease or better response): IV: 36 mg/m2 on days 1 and 2 every 8 weeks for 8 cycles (in combination with dexamethasone and rituximab) (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.
Kidney impairment prior to treatment initiation:
Note: During treatment, monitor serum creatinine and kidney function closely; new-onset acute kidney injury or severe kidney dysfunction may occur in carfilzomib-treated patients. One population-based study observed a rate of new-onset kidney failure as high as 22%. In addition, case reports of thrombotic microangiopathy have been described with use (Ref).
Altered kidney function: No dosage adjustment necessary (Ref).
Hemodialysis, intermittent (thrice weekly): Unlikely to be significantly dialyzable (high protein binding): No supplemental dose or dosage adjustment necessary (Ref).
Peritoneal dialysis: Unlikely to be significantly dialyzable (Ref): No dosage adjustment necessary (Ref).
CRRT: No dosage adjustment likely to be necessary (Ref).
PIRRT (eg, sustained, low-efficiency diafiltration): No dosage adjustment likely to be necessary (Ref).
Kidney toxicity during treatment: Serum creatinine ≥2 times baseline, CrCl <15 mL/minute or CrCl decreases to ≤50% of baseline, or patient requires hemodialysis: Withhold dose and monitor kidney function. If renal toxicity is due to carfilzomib, resume dosing when kidney function has improved to within 25% of baseline; resume with a reduced dose by 1 dose level (see "Dosing: Adjustment for Toxicity" for dose level reductions). If toxicity is not due to carfilzomib, restart at the discretion of the prescriber.
Hepatic impairment prior to treatment initiation:
Mild (total bilirubin 1 to 1.5 times ULN and any AST or total bilirubin ≤ULN and AST >ULN) or moderate (total bilirubin >1.5 to 3 times ULN and any AST) impairment: Reduce carfilzomib dose by 25%.
Severe (bilirubin > 3 times ULN) impairment: There are no dosage adjustments provided in the manufacturer's labeling (a recommended dose has not been in established in patients with bilirubin >3 times ULN and any AST).
Hepatotoxicity during treatment: Grade 3 or 4 elevation of bilirubin, transaminases, or other liver abnormalities: Withhold dose until resolved or at baseline. After resolution, if appropriate to reinitiate, consider restarting at 1 dose level reduction (see Dosing: Adjustment for Toxicity for dose level reductions) with frequent monitoring of hepatic function.
ASCO Guidelines for appropriate chemotherapy dosing in adults with a BMI ≥30 kg/m2 with cancer: In general, utilize patient's actual body weight for calculation of BSA- or weight-based dosing, manage regimen-related toxicities in the same manner as for patients with a BMI <30 kg/m2; if a dose reduction is utilized due to toxicity, may consider resumption of full weight-based dosing (or previously tolerated dose level) with subsequent cycles only if dose escalations are allowed in the prescribing information, if contributing underlying factors (eg, hepatic or renal impairment) are sufficiently resolved AND if performance status has markedly improved or is considered adequate (Ref). Note: According to the manufacturer, patients with a BSA >2.2 m2 should be dosed based upon a maximum BSA of 2.2 m2; dose adjustments for weight changes of ≤20% are not necessary.
Carfilzomib dose level reductions for toxicity:
|
Regimen |
Usual dose |
First dose reduction |
Second dose reduction |
Third dose reduction |
|---|---|---|---|---|
|
a Infusion times remain unchanged during dose reduction(s). Concomitant combination anticancer therapies may also require dosage modification; refer to those monographs for dosage adjustment recommendations. | ||||
|
b If toxicity persists, discontinue carfilzomib treatment. | ||||
|
Carfilzomib, lenalidomide, and dexamethasone; or carfilzomib monotherapy (twice weekly) |
27 mg/m2 |
20 mg/m2 |
15 mg/m2 b |
|
|
Carfilzomib and dexamethasone; or carfilzomib, daratumumab or daratumumab/hyaluronidase, and dexamethasone; or carfilzomib, isatuximab, and dexamethasone; or carfilzomib monotherapy (twice weekly) |
56 mg/m2 |
45 mg/m2 |
36 mg/m2 |
27 mg/m2 b |
|
Carfilzomib and dexamethasone; or carfilzomib, daratumumab or daratumumab/hyaluronidase, and dexamethasone (once weekly) |
70 mg/m2 |
56 mg/m2 |
45 mg/m2 |
36 mg/m2 b |
|
Adverse reaction |
Severity |
Carfilzomib dosage modification |
|---|---|---|
|
a PRES = posterior reversible encephalopathy syndrome; TTP/HUS = thrombocytopenic thrombotic purpura/hemolytic uremic syndrome | ||
|
Hematologic toxicity | ||
|
Neutropenia |
ANC <500/mm3 |
Withhold carfilzomib dose until ANC recovers to ≥500/mm3; resume at the same dose level. For subsequent ANC levels <500/mm3, withhold carfilzomib dose until ANC ≥500/mm3; consider reducing dose by 1 dose level when resuming carfilzomib. |
|
Neutropenic fever |
ANC <500/mm3 with an oral temperature >38.5°C or 2 consecutive readings of >38°C for 2 hours |
Withhold carfilzomib dose; if ANC recovers to baseline and fever resolves, resume at the same dose level. |
|
Thrombocytopenia |
Platelets <10,000/mm3 or evidence of bleeding with thrombocytopenia |
Withhold carfilzomib dose until platelets recover to ≥10,000/mm3 and/or bleeding is controlled; resume at the same dose level. For subsequent platelet levels <10,000/mm3, withhold carfilzomib dose until platelets ≥10,000/mm3; consider reducing dose by 1 dose level when resuming carfilzomib. |
|
Nonhematologic toxicity | ||
|
Cardiotoxicity |
Grade 3 or 4, new-onset or worsening of heart failure, decreased left ventricular function, or myocardial ischemia |
Withhold carfilzomib dose until resolved or at baseline. After resolution, if considered appropriate to reinitiate, consider restarting at 1 dose level reduction. |
|
Hemorrhage or symptoms of blood loss |
Any |
Reduce carfilzomib dose or withhold treatment as clinically appropriate. |
|
Hypertension |
Severe or life-threatening |
If hypertension cannot be adequately controlled, withhold carfilzomib dose and evaluate. After resolution, consider if appropriate to reinitiate based on risk versus benefit. |
|
PRES |
Suspected |
Discontinue carfilzomib if PRES diagnosis is suspected; the safety of reinitiating therapy after PRES diagnosis is not known. |
|
Progressive multifocal leukoencephalopathy |
Suspected |
Discontinue carfilzomib if progressive multifocal leukoencephalopathy is suspected; refer to a neurologist. |
|
Pulmonary toxicity |
Drug-induced acute respiratory distress syndrome, acute respiratory failure, and acute diffuse infiltrative pulmonary disease (eg, pneumonitis or interstitial lung disease) |
Discontinue carfilzomib. |
|
Pulmonary hypertension |
Withhold carfilzomib dose until resolved or at baseline. Perform cardiac imaging or other testing as appropriate. After resolution, consider if appropriate to reinitiate based on risk versus benefit. | |
|
Grade 3 or 4 dyspnea |
Withhold carfilzomib dose until resolved or at baseline. After resolution, consider if appropriate to reinitiate based on risk versus benefit. | |
|
Thrombotic microangiopathy |
Suspected |
Interrupt carfilzomib and manage appropriately if thrombotic microangiopathy, including TTP/HUS diagnosis is suspected. If TTP/HUS diagnosis is excluded, may consider reinitiating therapy; the safety of restarting carfilzomib after a TTP/HUS diagnosis is not known. |
|
Tumor lysis syndrome |
Uncontrolled |
Interrupt carfilzomib treatment and manage promptly until resolved. |
|
Other nonhematologic adverse reactions |
Grade 3 or 4 |
Withhold carfilzomib dose until resolved or at baseline. After resolution, consider restarting the next scheduled treatment at 1 dose level reduction. |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Adverse reactions reported from monotherapy studies in adults.
>10%:
Cardiovascular: Cardiac arrhythmia (13%) (Siegel 2013), chest pain (3% to 21%), hypertension (15% to 42%; including hypertensive crisis), peripheral edema (20% to 21%)
Endocrine & metabolic: Hypokalemia (14%) (Siegel 2013), hypomagnesemia (14%) (Siegel 2013)
Gastrointestinal: Constipation (11%) (Siegel 2013), decreased appetite (15% to 21%), diarrhea (25% to 27%; grades ≥3: 1% to 4%), nausea (35% to 54%; grades ≥3: 1%), vomiting (17% to 33%; grades ≥3: 1%)
Hematologic & oncologic: Anemia (42% to 49%; grades ≥3: 24% to 29%), leukopenia (11%; grade 3/4: 5%) (Siegel 2013), lymphocytopenia (14% to 33%; grades ≥3: 12% to 33%), neutropenia (16%; grade 3/4: 18%) (Siegel 2013), thrombocytopenia (37% to 54%; grades ≥3: 25% to 54%)
Nervous system: Chills (12% to 38%), dizziness (11% to 29%), fatigue (40% to 58%), headache (24% to 33%), insomnia (13% to 29%), peripheral neuropathy (≤19%; including dysesthesia, hypoesthesia, neuralgia, paresthesia, peripheral motor neuropathy, peripheral sensory neuropathy) (Siegel 2013)
Neuromuscular & skeletal: Back pain (19% to 21%), muscle spasm (10% to 21%)
Renal: Increased serum creatinine (17% to 25%), renal insufficiency (13%) (Siegel 2013)
Respiratory: Cough (22% to 33%), dyspnea (34% to 58%), upper respiratory tract infection (19% to 21%)
Miscellaneous: Fever (30% to 58%)
1% to 10%:
Cardiovascular: Cardiomyopathy (2%) (Siegel 2013), heart failure (7%) (Siegel 2013), ischemic heart disease (3%) (Siegel 2013), venous thromboembolism (2%; including deep vein thrombosis and pulmonary embolism)
Endocrine & metabolic: Hypercalcemia (grades ≥3: 4%) (Siegel 2013), hyperglycemia (grades ≥3: ≤4%), hyperkalemia (grades ≥3: ≤4%), hypocalcemia (grades ≥3: ≤4%), hyponatremia (grades ≥3: 7%) (Siegel 2013), hypophosphatemia (grades ≥3: 5%) (Siegel 2013)
Hematologic & oncologic: Febrile neutropenia (1%) (Seigel 2013)
Renal: Acute kidney injury (5%), renal failure syndrome (4%) (Siegel 2013)
Respiratory: Pleural effusion (4%) (Siegel 2013), pneumonia (8%), pulmonary hypertension (2%) (Siegel 2013)
<1%:
Hematologic & oncologic: Tumor lysis syndrome (Siegel 2013)
Respiratory: Hemoptysis (Siegel 2013), pneumonitis (Siegel 2013)
Frequency not defined:
Cardiovascular: Acute myocardial infarction, hypotension, reduced ejection fraction, thromboembolic complications
Dermatologic: Erythema of skin, hyperhidrosis, pruritus, skin rash
Endocrine & metabolic: Hyperuricemia, hypoalbuminemia
Gastrointestinal: Abdominal pain, dyspepsia, toothache, upper abdominal pain
Genitourinary: Urinary tract infection
Hematologic & oncologic: Hemorrhage (including epistaxis, gastrointestinal hemorrhage, intracranial hemorrhage, pulmonary hemorrhage)
Hepatic: Hepatic failure, increased serum transaminases (including increased serum alanine aminotransferase and increased serum aspartate aminotransferase) (Siegel 2013)
Hypersensitivity: Infusion-related reaction
Infection: Influenza, sepsis
Local: Infusion-site reaction
Nervous system: Anxiety, asthenia, pain, voice disorder
Neuromuscular & skeletal: Arthralgia, limb pain, musculoskeletal chest pain, musculoskeletal pain, myalgia
Ophthalmic: Blurred vision, cataract
Otic: Tinnitus
Respiratory: Acute respiratory distress syndrome, acute respiratory failure, bronchitis, bronchopneumonia, nasopharyngitis, oropharyngeal pain, pulmonary disease (acute diffuse infiltrative, including interstitial pulmonary disease), pulmonary edema, pulmonary infection, respiratory tract infection, rhinitis
Miscellaneous: Multi-organ failure
Postmarketing (may include combination therapy):
Cardiovascular: Pericarditis
Gastrointestinal: Acute pancreatitis, enterocolitis, gastrointestinal perforation, intestinal obstruction
Hematologic & oncologic: Hemolytic-uremic syndrome, thrombotic microangiopathy, thrombotic thrombocytopenic purpura
Infection: Cytomegalovirus disease, reactivation of HBV, viremia
Nervous system: Progressive multifocal leukoencephalopathy, reversible posterior leukoencephalopathy syndrome
Ophthalmic: Chorioretinitis
There are no contraindications listed in the manufacturer's US labeling.
Canadian labeling: Hypersensitivity to carfilzomib or any component of the formulation.
Concerns related to adverse effects:
• Bone marrow suppression: Thrombocytopenia (including grade 4) was observed in patients receiving carfilzomib, with platelet nadirs occurring between day 8 and day 15 of each 28-day treatment cycle and recovery to baseline by the start of the next cycle. Hemorrhage due to thrombocytopenia may occur.
• Cardiovascular effects: Carfilzomib has been associated with new-onset or worsening of heart failure, pulmonary edema, decreased ejection fraction, cardiomyopathy, myocardial ischemia, and myocardial infarction (MI) (including fatalities). Some events occurred in patients with normal ventricular function at baseline. Cardiac events typically were observed throughout the course of therapy. Death caused by cardiac arrest has occurred within 1 day of carfilzomib administration. Patients ≥75 years of age have an increased risk of heart failure. Patients with NYHA class III and IV heart failure, recent MI (within 3 to 6 months), and conduction abnormalities, angina, or arrhythmias not managed by medication were excluded from clinical trials and may be at increased risk for cardiac complications; evaluate with a comprehensive medical assessment prior to initiation and closely monitor.
• Hemorrhage: Serious or fatal cases of hemorrhage have been reported, including GI, intracranial, and pulmonary hemorrhage and epistaxis. Bleeding may be spontaneous; intracranial hemorrhage has occurred without trauma. Hemorrhage has been reported in patients with normal or low platelet counts and has also been reported in patients who were not receiving anticoagulation or antiplatelet therapy.
• Hepatic effects: Hepatic failure, including fatal cases, has been reported rarely. Increased transaminases and hyperbilirubinemia have also been observed.
• Hypertension: Hypertension has occurred with carfilzomib; hypertensive crisis and hypertensive emergency have also been reported (some events were fatal).
• Infusion-related reactions: May occur immediately following or within 24 hours of carfilzomib infusion; may be life-threatening. Signs/symptoms have included fever, chills, arthralgia, myalgia, flushing, facial or laryngeal edema, vomiting, weakness, dyspnea, hypotension, syncope, chest tightness, or angina.
• Kidney toxicity: Renal insufficiency, acute kidney failure, and kidney failure have been reported with carfilzomib; some events have been fatal. Acute kidney failure was observed more frequently in patients receiving carfilzomib monotherapy for advanced relapsed or refractory multiple myeloma; kidney failure risk is greater when patients have a baseline reduced CrCl.
• Posterior reversible encephalopathy syndrome: Posterior reversible encephalopathy syndrome (PRES) has been reported rarely with use; symptoms include seizure, headache, lethargy, confusion, blindness, altered consciousness, hypertension, and other visual/neurological disturbances.
• Progressive multifocal leukoencephalopathy: Progressive multifocal leukoencephalopathy (PML), which may be fatal, has been reported; prior or concurrent immunosuppressive therapy may be a contributory factor. Consider PML with new-onset or changes in preexisting neurological signs or symptoms.
• Pulmonary toxicities: Acute respiratory distress syndrome (ARDS), acute respiratory failure, and acute diffuse-infiltrative pulmonary disease (eg, pneumonitis and interstitial lung disease) have occurred in a small percentage of patients (some events were fatal). In clinical trials, pulmonary arterial hypertension (PAH) was observed (including grade 3 or higher events). Dyspnea (including grade 3 or higher events) has been reported.
• Thrombotic microangiopathy: Thrombotic microangiopathy, including cases of thrombocytopenic thrombotic purpura/hemolytic uremic syndrome (TTP/HUS), has been reported (some fatal).
• Thromboembolic events: Venous thromboembolism (eg, deep vein thrombosis and pulmonary embolism) has been observed, particularly when used as part of combination therapy with dexamethasone or with lenalidomide plus dexamethasone.
• Tumor lysis syndrome: Tumor lysis syndrome (TLS), including fatalities, has been observed. TLS risk is increased in multiple myeloma patients with a high tumor burden.
Disease-related concerns:
• Hepatic impairment: The incidence of serious adverse events is higher in patients with mild, moderate, and severe baseline hepatic impairment combined (compared to patients with normal hepatic function).
Concurrent drug therapy issues:
• Combination therapy toxicity: An increased incidence of serious and fatal adverse events was observed in a clinical trial comparing the combination of carfilzomib, melphalan, and prednisone (KMP) to bortezomib, melphalan, and prednisone (VMP) for the treatment of newly diagnosed multiple myeloma (MM) in transplant-ineligible patients. Cardiac failure, hypertension, acute kidney failure, and dyspnea were observed more frequently in the KMP arm. KMP is not an approved carfilzomib combination regimen.
Special populations:
• Older adult: The incidence of serious adverse events is higher in patients ≥65 years of age (compared to patients <65 years of age).
Dosage form specific issues:
• Excipient: Carfilzomib contains the excipient cyclodextrin (sulfobutyl ether beta-cyclodextrin), which may accumulate in patients with renal insufficiency, although the clinical significance of this finding is uncertain (Luke 2010).
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Kyprolis: 10 mg (1 ea); 30 mg (1 ea); 60 mg (1 ea)
No
Solution (reconstituted) (Kyprolis Intravenous)
10 mg (per each): $707.44
30 mg (per each): $2,122.32
60 mg (per each): $4,244.63
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Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Reconstituted, Intravenous:
Kyprolis: 10 mg (1 ea); 30 mg (1 ea); 60 mg (1 ea)
IV: Administer over 10 or 30 minutes depending on the carfilzomib dose regimen. Do not administer as an IV push or bolus. Hydrate with oral fluids (30 mL/kg) at least 48 hours prior to initiating cycle 1, as well as with 250 to 500 mL NS (or other appropriate IV fluid) prior to (recommended) and after (if needed) each dose in cycle 1; continue oral and/or IV hydration in subsequent cycles (if necessary). Flush line immediately before and after carfilzomib with NS or D5W. Do not administer with other medications.
When administering as monotherapy, premedicate with dexamethasone 4 mg orally or IV when infusing carfilzomib over 10 minutes or with dexamethasone 8 mg orally or IV when infusing carfilzomib over 30 minutes. When using combination therapy, administer the recommended dexamethasone dose (refer to prescribing information). Premedicate 30 minutes to 4 hours prior to all carfilzomib doses in cycle 1, and as needed with future cycles to reduce the incidence and severity of infusion reaction.
Hazardous agent (NIOSH 2024 [table 2]).
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2023; NIOSH 2024; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Multiple myeloma, relapsed or refractory:
Treatment (as a single agent) of relapsed or refractory multiple myeloma in adults who have received 1 or more lines of therapy.
Treatment of relapsed or refractory multiple myeloma (in combination with dexamethasone, or with lenalidomide plus dexamethasone, or with daratumumab plus dexamethasone, or with daratumumab/hyaluronidase plus dexamethasone, or with isatuximab plus dexamethasone) in adults who have received 1 to 3 prior lines of therapy.
Heart transplantation, desensitization; Kidney transplantation, desensitization; Lung transplantation, antibody-mediated rejection, treatment; Multiple myeloma, newly diagnosed; Waldenström macroglobulinemia
Carfilzomib may be confused with bortezomib, ixazomib
The Institute for Safe Medication Practices (ISMP) includes this medication among its list of drug classes (chemotherapeutic agent, parenteral and oral) which have a heightened risk of causing significant patient harm when used in error (High-Alert Medications in Acute Care, Community/Ambulatory Care, and Long-Term Care Settings).
Substrate of P-glycoprotein (Minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential;
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the drug interactions program by clicking on the “Launch drug interactions program” link above.
5-Aminosalicylic Acid Derivatives: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Abrocitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Androgens: Hypertension-Associated Agents may increase hypertensive effects of Androgens. Risk C: Monitor
Antithymocyte Globulin (Equine): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor
Antithyroid Agents: Myelosuppressive Agents may increase neutropenic effects of Antithyroid Agents. Risk C: Monitor
Baricitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Baricitinib. Risk X: Avoid
BCG Products: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of BCG Products. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of BCG Products. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Brincidofovir: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Brincidofovir. Risk C: Monitor
Brivudine: May increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Chikungunya Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Chikungunya Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Chikungunya Vaccine (Live). Risk X: Avoid
Chloramphenicol (Ophthalmic): May increase adverse/toxic effects of Myelosuppressive Agents. Risk C: Monitor
Chloramphenicol (Systemic): Myelosuppressive Agents may increase myelosuppressive effects of Chloramphenicol (Systemic). Risk X: Avoid
Cladribine: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Cladribine. Risk X: Avoid
CloZAPine: Myelosuppressive Agents may increase adverse/toxic effects of CloZAPine. Specifically, the risk for neutropenia may be increased. Risk C: Monitor
Coccidioides immitis Skin Test: Coadministration of Immunosuppressants (Miscellaneous Oncologic Agents) and Coccidioides immitis Skin Test may alter diagnostic results. Management: Consider discontinuing these oncologic agents several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Inactivated Virus): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Inactivated Virus). Risk C: Monitor
COVID-19 Vaccine (mRNA): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (mRNA). Management: Give a 3-dose primary series for all patients aged 6 months and older taking immunosuppressive medications or therapies. Booster doses are recommended for certain age groups. See CDC guidance for details. Risk D: Consider Therapy Modification
COVID-19 Vaccine (Subunit): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of COVID-19 Vaccine (Subunit). Risk C: Monitor
Deferiprone: Myelosuppressive Agents may increase neutropenic effects of Deferiprone. Management: Avoid the concomitant use of deferiprone and myelosuppressive agents whenever possible. If this combination cannot be avoided, monitor the absolute neutrophil count more closely. Risk D: Consider Therapy Modification
Dengue Tetravalent Vaccine (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Dengue Tetravalent Vaccine (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Dengue Tetravalent Vaccine (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Denosumab: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor patients for signs/symptoms of serious infections. Risk D: Consider Therapy Modification
Deucravacitinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Etrasimod: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Fexinidazole: Myelosuppressive Agents may increase myelosuppressive effects of Fexinidazole. Risk X: Avoid
Filgotinib: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Hormonal Contraceptives: May increase thrombogenic effects of Carfilzomib. Management: Consider alternative, non-hormonal methods of contraception in patients requiring therapy with carfilzomib, especially patients using carfilzomib in combination with dexamethasone, lenalidomide plus dexamethasone, or daratumumab plus dexamethasone. Risk D: Consider Therapy Modification
Inebilizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Inebilizumab. Risk C: Monitor
Influenza Virus Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Influenza Virus Vaccines. Management: Administer influenza vaccines at least 2 weeks prior to initiating immunosuppressants if possible. If vaccination occurs less than 2 weeks prior to or during therapy, revaccinate at least 3 months after therapy discontinued if immune competence restored. Risk D: Consider Therapy Modification
Leflunomide: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider Therapy Modification
Linezolid: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Mumps- Rubella- or Varicella-Containing Live Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Mumps- Rubella- or Varicella-Containing Live Vaccines. Mumps- Rubella- or Varicella-Containing Live Vaccines may increase adverse/toxic effects of Immunosuppressants (Miscellaneous Oncologic Agents). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Nadofaragene Firadenovec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid
Natalizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Natalizumab. Risk X: Avoid
Ocrelizumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ocrelizumab. Risk C: Monitor
Ofatumumab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ofatumumab. Risk C: Monitor
Olaparib: Myelosuppressive Agents may increase myelosuppressive effects of Olaparib. Risk C: Monitor
Pidotimod: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pidotimod. Risk C: Monitor
Pimecrolimus: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk X: Avoid
Pneumococcal Vaccines: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Pneumococcal Vaccines. Risk C: Monitor
Poliovirus Vaccine (Live/Trivalent/Oral): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Poliovirus Vaccine (Live/Trivalent/Oral). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Polymethylmethacrylate: Immunosuppressants (Miscellaneous Oncologic Agents) may increase hypersensitivity effects of Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider Therapy Modification
Promazine: May increase myelosuppressive effects of Myelosuppressive Agents. Risk C: Monitor
Rabies Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Rabies Vaccine. Management: Complete rabies vaccination at least 2 weeks before initiation of immunosuppressant therapy if possible. If combined, check for rabies antibody titers, and if vaccination is for post exposure prophylaxis, administer a 5th dose of the vaccine. Risk D: Consider Therapy Modification
Ritlecitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ritlecitinib. Risk X: Avoid
Ropeginterferon Alfa-2b: Myelosuppressive Agents may increase myelosuppressive effects of Ropeginterferon Alfa-2b. Management: Avoid coadministration of ropeginterferon alfa-2b and other myelosuppressive agents. If this combination cannot be avoided, monitor patients for excessive myelosuppressive effects. Risk D: Consider Therapy Modification
Ruxolitinib (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ruxolitinib (Topical). Risk X: Avoid
Sipuleucel-T: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider Therapy Modification
Solriamfetol: May increase hypertensive effects of Hypertension-Associated Agents. Risk C: Monitor
Sphingosine 1-Phosphate (S1P) Receptor Modulators: May increase immunosuppressive effects of Immunosuppressants (Miscellaneous Oncologic Agents). Risk C: Monitor
Tacrolimus (Topical): Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tacrolimus (Topical). Risk X: Avoid
Talimogene Laherparepvec: Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid
Tertomotide: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Tertomotide. Risk X: Avoid
Tofacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Tofacitinib. Risk X: Avoid
Typhoid Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Typhoid Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Typhoid Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Ublituximab: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Ublituximab. Risk C: Monitor
Upadacitinib: Immunosuppressants (Miscellaneous Oncologic Agents) may increase immunosuppressive effects of Upadacitinib. Risk X: Avoid
Vaccines (Live): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Live). Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Vaccines (Live). Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Vaccines (Non-Live/Inactivated/Non-Replicating): Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Vaccines (Non-Live/Inactivated/Non-Replicating). Management: Give non-live/inactivated/non-replicating vaccines at least 2 weeks prior to initiation of immunosuppressants when possible. Patients vaccinated less than 14 days before or during therapy should be revaccinated at least 3 months after therapy is complete. Risk D: Consider Therapy Modification
Yellow Fever Vaccine: Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Yellow Fever Vaccine. Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Yellow Fever Vaccine. Specifically, the risk of vaccine-associated infection may be increased. Risk X: Avoid
Zoster Vaccine (Live/Attenuated): Immunosuppressants (Miscellaneous Oncologic Agents) may increase adverse/toxic effects of Zoster Vaccine (Live/Attenuated). Specifically, the risk of vaccine-associated infection may be increased. Immunosuppressants (Miscellaneous Oncologic Agents) may decrease therapeutic effects of Zoster Vaccine (Live/Attenuated). Risk X: Avoid
Conduct pregnancy testing prior to treatment initiation in patients who could become pregnant. Patients who could become pregnant should avoid pregnancy during carfilzomib treatment and use effective contraception during treatment and for 6 months after the last carfilzomib dose. Due to risk of thrombosis with hormonal contraception, consider an alternative method of effective contraception during combination treatment of carfilzomib with dexamethasone, lenalidomide plus dexamethasone, or daratumumab plus dexamethasone.
Patients with partners who could become pregnant should use effective contraception during treatment and for 3 months after the last carfilzomib dose.
Carfilzomib may impair fertility in males and females (based on the mechanism of action).
Based on the mechanism of action and findings from animal reproduction studies, in utero exposure to carfilzomib may cause fetal harm.
It is not known if carfilzomib is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during carfilzomib treatment and for 2 weeks after the last dose of carfilzomib.
CBC with differential and platelets (monitor frequently throughout therapy), serum potassium levels regularly during treatment, kidney function, pulmonary function (with new or worsening pulmonary symptoms), LFTs (regularly), BP (regularly throughout treatment in all patients). Pregnancy test (prior to treatment initiation) in patients who could become pregnant. Monitor for signs/symptoms of infusion-related reactions, congestive heart failure, hemorrhage (promptly evaluate symptoms of blood loss), tumor lysis syndrome, peripheral neuropathy, posterior reversible encephalopathy syndrome, progressive multifocal leukoencephalopathy, thrombocytopenic thrombotic purpura/hemolytic uremic syndrome, and venous thromboembolic events. Monitor closely for cardiac complications and evidence of volume overload due to pre- and post-hydration, particularly in patients at risk for heart failure.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow up.
Cardiovascular monitoring: Comprehensive assessment prior to treatment including a history and physical examination, screening for cardiovascular disease risk factors such as hypertension, diabetes, dyslipidemia, obesity, and smoking (ASCO [Armenian 2017], (ESC [Lyon 2022]). Assess BP at baseline and each clinical visit (also consider weekly home monitoring for initial 3 months, then monthly thereafter); assess natriuretic peptide at baseline for high and very high-risk patients and consider at each cycle for the first 6 cycles; consider checking natriuretic peptide at baseline for low- and moderate-risk patients; obtain a baseline echocardiography in all patients; repeat echocardiography every 3 cycles in high- and very-high risk patients and consider echocardiography every 3 cycles in low- and moderate-risk patients (ESC [Lyon 2022]).
Carfilzomib inhibits proteasomes, which are responsible for intracellular protein homeostasis. Specifically, it is a potent, selective, and irreversible inhibitor of chymotrypsin-like activity of the 20S proteasome, leading to cell cycle arrest and apoptosis.
Distribution: Vdss: 28 L (based on a 20 mg/m2 dose); penetrates all tissues extensively except the brain (Kortuem 2013).
Protein binding: 97%; to human plasma proteins.
Metabolism: Rapidly metabolized; primarily via peptidase cleavage and epoxide hydrolysis; minimal metabolism through cytochrome P450-mediated mechanisms.
Half-life elimination: Doses ≥15 mg/m2: ≤1 hour on day 1 of cycle 1.
Excretion: Urine (~25% as metabolites; <1% as parent drug); feces (<1% as parent drug).
Clearance: 151 to 263 L/hour.
Altered kidney function: Patients with end-stage kidney disease requiring hemodialysis had a 33% higher AUC compared to patients with normal kidney function.
Hepatic function impairment: Patients with mild (total bilirubin 1 to 1.5 times ULN and any AST or total bilirubin ≤ULN and AST >ULN) or moderate (bilirubin >1.5 to 3 times ULN and any AST) hepatic impairment had an approximately 50% higher AUC compared to patients with normal hepatic function.
