Carfilzomib

Reviewed on 5/11/2022

SLIDESHOW

Understanding Cancer: Metastasis, Stages of Cancer, and More See Slideshow

What Are Dosages of Carfilzomib?

Adult dosage

Injection, lyophilized powder for reconstitution

  • 10mg/vial
  • 30mg/vial
  • 60mg/vial

Multiple myeloma

Adult dosage

  • Combination with dexamethasone (once-weekly regimen)
  • Each cycle is 28 days
  • Administer dexamethasone 30 min - 4 hr before carfilzomib; refer to prescribing information for dexamethasone for additional dosage information
  • Cycle 1
    • Carfilzomib 20 mg/m2 IV Day 1; if tolerated escalate dose to 70 mg/m2 on Days 8 and 15 PLUS  
    • Dexamethasone 40 mg orally/IV on Days 1, 8, 15, 22
  • Cycle 2-9
    • Carfilzomib 70 mg/m2 IV on Days 1, 8, 15 PLUS
    • Dexamethasone 40 mg orally/IV on Days 1, 8, 15, 22
  • Cycle 10 and thereafter
    • Carfilzomib 70 mg/m2 IV on Days 1, 8, 15 PLUS
    • Dexamethasone 40 mg orally/IV on Days 1, 8, 15
    • Continue until disease progression or unacceptable toxicity occurs
    • Combination with dexamethasone (twice weekly regimen)
  • Each cycle is 28 days
  • Administer dexamethasone 30 min - 4 hr before carfilzomib; refer to prescribing information for dexamethasone for additional dosage information
  • Cycle 1
    • Carfilzomib 20 mg/m2 IV Days 1 and 2; if tolerated escalate dose to 56 mg/m2 on Days 8, 9, 15, 16 PLUS  
    • Dexamethasone 20 mg PO/IV on Days 1, 2, 8, 9, 15, 16, 22, 23
  • Cycles 2 and thereafter
    • Carfilzomib 56 mg/m2 IV on Days 1, 2, 8, 9, 15, 16 PLUS
    • Dexamethasone 20 mg orally/IV on Days 1, 2, 8, 9, 15, 16, 22, 23
    • Continue until disease progression or unacceptable toxicity occurs
    • Combination with lenalidomide and dexamethasone
  • Each cycle is 28 days
  • Administer dexamethasone 30 min - 4 hr before carfilzomib; refer to prescribing information for lenalidomide and dexamethasone for additional dosage information
  • Cycle 1
    • Carfilzomib 20 mg/m2 IV Days 1 and 2; if tolerated escalate dose to 27 mg/m2 on Days 8, 9, 15, 16 PLUS  
    • Lenalidomide 25 mg orally on Days 1–21 PLUS
    • Dexamethasone 40 mg orally/IV on Days 1, 8, 15, 22
  • Cycles 2-12
    • Carfilzomib 27 mg/m2 IV on Days 1, 2, 8, 9, 15, 16 PLUS
    • Lenalidomide 25 mg orally on Days 1–21 PLUS
    • Dexamethasone 40 mg orally/IV on Days 1, 8, 15, 22
  • Cycles 13 -18
    • Carfilzomib 27 mg/m2 IV on Days 1, 2, 15, 16 PLUS
    • Lenalidomide 25 mg orally on Days 1–21 PLUS
    • Dexamethasone 40 mg orally/IV on Days 1, 8, 15, 22
  • Cycles 19 and thereafter
    • Lenalidomide 25 mg orally on Days 1–21 PLUS
    • Dexamethasone 40 mg orally or IV on Days 1, 8, 15, 22
    • Continue until disease progression or unacceptable toxicity
    • Combination with daratumumab OR daratumumab/hyaluronidase and dexamethasone (once-weekly regimen)
  • Each cycle is 28 days
    • Administer dexamethasone 30 min - 4 hr before carfilzomib and 1-3 hr before IV daratumumab; refer to prescribing information for daratumumab IV and dexamethasone for additional dosage information
    • Patients aged above 75 years administer dexamethasone 20 mg orally/IV after the first week
  • Cycle 1
    • Carfilzomib 20 mg/m2 IV Day 1; if tolerated escalate dose to 70 mg/m2 on Days 8 and 15 PLUS
    • Dexamethasone 20 mg orally/IV on Days 1, 2, 8, 9, 15, 16, 22, 23 PLUS
    • Daratumumab 8 mg/kg IV Days 1 and 2; if tolerated escalated dose to 16 mg/kg on Days 8, 15, 22 OR
    • Daratumumab/hyaluronidase 1,800 mg/30,000 units SC on Days 1, 8, 15, 22
  • Cycle 2
    • Carfilzomib 70 mg/m2 IV on Days 1, 8, 15, PLUS
    • Dexamethasone 20 mg orally/IV on Days 1, 2, 8, 9, 15, 16, 22, 23 PLUS
    • Daratumumab 16 mg/kg IV on Days 1, 8, 15, 22, OR
    • Daratumumab/hyaluronidase 1,800 mg/30,000 units SC on Days 1, 8, 15, 22
  • Cycles 3-6
    • Carfilzomib 70 mg/m2 IV on Days 1, 8, 15, PLUS
    • Dexamethasone 20 mg orally/IV on Days 1, 2; then 40 mg on Day 8; then 20 mg on Days 15, 16; then 40 mg on Day 22 PLUS
    • Daratumumab 16 mg/kg IV on Days 1 and 15, OR
    • Daratumumab/hyaluronidase 1,800 mg/30,000 units SC on Days 1 and 15
  • Cycles 7 and thereafter
    • Carfilzomib 70 mg/m2 IV on Days 1, 8, 15 PLUS
    • Dexamethasone 20 mg orally/IV on Days 1, 2; then 40 mg orally/IV on Days 8, 15, 22 PLUS
    • Daratumumab 16 mg/kg IV on Day 1, OR
    • Daratumumab/hyaluronidase 1,800 mg/30,000 units SC on Day 1
    • Continue until disease progression or unacceptable toxicity occurs
    • Combination with daratumumab OR daratumumab/hyaluronidase and dexamethasone (twice weekly regimen)
  • Each cycle is 28 days
  • Administer dexamethasone 30 min - 4 hr before carfilzomib and 1-3 hr before IV daratumumab; refer to prescribing information for daratumumab IV and dexamethasone for additional dosage information
  • Cycle 1
    • Carfilzomib 20 mg/m2 IV Days 1 and 2; if tolerated escalate dose to 56 mg/m2 on Days 8, 9, 15, 16, PLUS
    • Dexamethasone 20 mg orally/IV on Days 1, 2, 8, 9, 15, 16, 22, 23 PLUS
    • Daratumumab 8 mg/kg IV Days 1 and 2; if tolerated escalated dose to 16 mg/kg on Days 8, 15, 22 OR
    • Daratumumab/hyaluronidase 1,800 mg/30,000 units SC on Days 1, 8, 15, 22
  • Cycle 2
    • Carfilzomib 56 mg/m2 IV on Days 1, 2, 8, 9, 15, 16 PLUS
    • Dexamethasone 20 mg PO/IV on Days 1, 2, 8, 9, 15, 16, 22, 23 PLUS
    • Daratumumab 16 mg/kg IV on Days 1, 8, 15, 22, OR
    • Daratumumab/hyaluronidase 1,800 mg/30,000 units SC on Days 1, 8, 15, 22
  • Cycles 3-6
    • Carfilzomib 56 mg/m2 IV on Days 1, 2, 8, 9, 15, 16 PLUS
    • Dexamethasone 20 mg orally/IV on Days 1, 2, 8, 9, 15, 16; then 40 mg on Day 22 PLUS
    • Daratumumab 16 mg/kg IV on Days 1 and 15, OR
    • Daratumumab/hyaluronidase 1,800 mg/30,000 units SC on Days 1 and 15
  • Cycles 7 and thereafter
    • Carfilzomib 56 mg/m2 IV on Days 1, 2, 8, 9, 15, 16, PLUS
    • Dexamethasone 20 mg orally/IV on Days 1, 2, 8, 9, 15, 16; then 40 mg orally/IV on Day 22 PLUS
    • Daratumumab 16 mg/kg IV on Day 1, OR
    • Daratumumab/hyaluronidase 1,800 mg/30,000 units SC on Day 1
    • Continue until disease progression or unacceptable toxicity occurs
    • Monotherapy
    • Each cycle is 28 days
    • 20/27 mg/m2 twice weekly regimen (10-min infusion)
      • Cycle 1: Carfilzomib 20 mg/m2 IV on Days 1 and 2; if tolerated, escalate to a escalate dose to 27 mg/m2 on Days 8, 9, 15, 16  
      • Cycles 2-12: Carfilzomib 27 mg/m2 IV on Days 1, 2, 8, 9, 15, and 16
      • Cycles 13 and thereafter: Carfilzomib 27 mg/m2 IV on Days 1, 2, 15, and 16; continue until disease progression or unacceptable toxicity
    • 20/56 mg/m2 twice weekly regimen (30-min infusion)
      • Cycle 1: Carfilzomib 20 mg/m2 IV on Days 1 and 2; if tolerated, escalate to a escalate dose to 56 mg/m2 on Days 8, 9, 15, 16
      • Cycles 2-12: Carfilzomib 56 mg/m2 IV on Days 1, 2, 8, 9, 15, and 16
      • Cycles 13 and thereafter: Carfilzomib 56 mg/m2 IV on Days 1, 2, 15, and 16; continue until disease progression or unacceptable toxicity

Dosage Considerations – Should be Given as Follows: 

  • See “Dosages”

What Are Side Effects Associated with Using Carfilzomib?

Common side effects of the Carfilzomib include:

Serious side effects of the Carfilzomib include:

  • severe ongoing stomach discomfort or diarrhea,
  • feeling very thirsty or hot,
  • unable to urinate,
  • heavy sweating, and
  • hot and dry skin

Rare side effects of the Carfilzomib include:

  • none 
This is not a complete list of side effects and other serious side effects or health problems that may occur as a result of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

What Other Drugs Interact with Carfilzomib?

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

  • Carfilzomib has severe interactions with no other drugs.
  • Carfilzomib has serious interactions with the following drugs:
    • erdafitinib
    • lasmiditan
    • palifermin
    • ropeginterferon alfa 2b
    • sotorasib
    • tepotinib
  • Carfilzomib has moderate interactions with the following drugs:
    • berotralstat
    • dichlorphenamide
    • elagolix
    • eliglustat
    • fostamatinib
    • glecaprevir/pibrentasvir
    • istradefylline
    • ponesimod
    • sarecycline
    • siponimod
    • stiripentol
    • tucatinib
  • Carfilzomib has minor interactions with no other drugs.

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your health care professional or doctor for additional medical advice, or if you have health questions or concerns.

What Are Warnings and Precautions for Carfilzomib?

Contraindications

  • None

Effects of drug abuse

  • None

Short-Term Effects

  • See “What Are Side Effects Associated with Using Carfilzomib?”

Long-Term Effects

  • See “What Are Side Effects Associated with Using Carfilzomib?”

Cautions

  • Also, see Dosage Modifications
  • Hydrate patients to reduce the risk of renal toxicity and tumor lysis syndrome (TLS) and premedicate to avoid infusion reactions; maintain adequate fluid volume status throughout treatment and monitor blood chemistries closely (see Administration)
  • Tumor lysis syndrome, including fatal outcomes, is reported; patients with multiple myeloma and a high tumor burden are at greater risk; ensure adequate hydration and consider uric acid-lowering drugs
  • Acute respiratory distress syndrome (ARDS) and acute respiratory failure were reported; acute diffuse infiltrative pulmonary disease, such as pneumonitis and interstitial lung disease also reported
  • Monitor for pulmonary hypertension and other pulmonary complications (eg, ARDS) during and after treatment completion; dyspnea reported in 31% of patients
  • Dyspnea reported; evaluate dyspnea to exclude cardiopulmonary conditions including cardiac failure and pulmonary syndromes
  • Consider neuroradiological imaging (MRI) for the onset of visual or neurological symptoms of posterior reversible encephalopathy syndrome (PRES); discontinue therapy if suspected
  • Monitor platelet counts; interrupt or reduce dosing as clinically indicated if thrombocytopenia occurs
  • Cases of hepatic failure, including fatal cases, are reported; monitor liver enzymes regularly, regardless of baseline values, and modify dose based on toxicity
  • Fatal or serious cases of hemorrhage may occur, including gastrointestinal, pulmonary, and intracranial hemorrhage; promptly evaluate signs and symptoms of blood loss; bleeding can be spontaneous; intracranial hemorrhage has occurred without trauma; also reported in patients having either low or normal platelet counts and in patients who were not on antiplatelet therapy or anticoagulation; evaluate signs and symptoms or blood loss promptly; withhold or reduce the dose as necessary
  • Increased fatal and serious toxicities reported in combination with melphalan and prednisone in newly diagnosed transplant-ineligible patients
  • Thrombocytopenia with platelet nadirs was observed between Day 8 and Day 15 of each 28-day cycle, with recovery to baseline platelet count usually by the start of the next cycle; thrombocytopenia was reported in up to 32% of patients in clinical trials with carfilzomib
  • Infusion-related reactions, including life-threatening reactions, were reported; signs and symptoms include fever, chills, arthralgia, myalgia, facial flushing, facial edema, laryngeal edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina; may occur immediately following or up to 24 hours after administration; administer dexamethasone before therapy to reduce incidence and severity of infusion-related reactions; inform patients of the risk and symptoms and to contact a healthcare provider immediately if symptoms of an infusion-related reaction occur
  • Progressive multifocal leukoencephalopathy (PML), which can be fatal, is reported; other possible contributory factors include prior or concurrent immunosuppressive therapy that may cause immunosuppression; consider PML in any patient with new-onset of or changes in pre-existing neurological signs or symptoms; if PML is suspected, discontinue therapy and initiate evaluation for PML including neurology consultation
  • Hypertension, including hypertensive crisis and hypertensive emergency, has been observed; optimize blood pressure before starting treatment; monitor blood pressure regularly in all patients while on therapy; if hypertension cannot be adequately controlled, withhold therapy and evaluate; consider whether to restart therapy based on a benefit/risk assessment
  • Can cause fetal harm (see Pregnancy)
  • Acute renal failure
    • Acute renal failure reported, including some fatalities
    • Renal insufficiency adverse events (including renal failure) were reported in up to 11%; acute renal failure was reported more frequently in patients with advanced relapsed and refractory multiple myeloma who received carfilzomib monotherapy
    • Reduce or interrupt dosage as described for toxicities accordingly (see Dosage Modification)
    • Thromboembolic events
    • Venous thromboembolic events (VTE) reported
    • Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), are reported; some cases have been fatal; monitor for signs and symptoms of TTP/HUS; discontinue therapy if suspected; if diagnosis of TTP/HUS is excluded, therapy may be restarted
    • Venous thromboembolic events (VTE), including DVT and PE, were observed in clinical trials; in the combination study, VTE incidence in the first 12 cycles was 13% in the carfilzomib combination arm vs 6 % in the control arm; with monotherapy, the incidence of VTE was 2%
    • Patients using oral contraceptives or a hormonal method of contraception associated with a risk of thrombosis should consider an alternative method of effective contraception during treatment with carfilzomib in combination with dexamethasone or lenalidomide plus dexamethasone
    • Thromboprophylaxis is recommended for patients being treated in combination with dexamethasone or with lenalidomide plus dexamethasone; the thromboprophylaxis regimen should be based on the assessment of the patient’s underlying risks
  • Cardiovascular risk
    • New onset or worsening of pre-existing cardiac failure (eg, congestive heart failure, pulmonary edema, decreased ejection fraction), restrictive cardiomyopathy, myocardial ischemia, and myocardial infarction including fatalities have occurred following administration of carfilzomib; some events occurred in patients with normal baseline ventricular function; monitor for signs and symptoms of cardiac failure or ischemia; withhold therapy and evaluate promptly
    • Patients experiencing cardiac failure or ischemia may be at greater risk for cardiac complications; perform a comprehensive medical assessment, including blood pressure and fluid management, before initiating treatment and continue close follow-up
    • While adequate hydration is required before each dose in Cycle 1, monitor all patients for evidence of volume overload, especially patients at risk for cardiac failure; adjust total fluid intake as clinically appropriate in patients with baseline cardiac failure or who are at risk for cardiac failure
    • Death due to cardiac arrest has occurred within a day of carfilzomib administration
    • Cardiac failure events (e.g., cardiac failure congestive, pulmonary edema, decreased ejection fraction) were reported in 7% of patients; monitor for signs and symptoms of cardiac failure or ischemia; withhold therapy and evaluate promptly
    • Monitor for cardiac complications and manage promptly
    • Optimize blood pressure before starting therapy; if blood pressure cannot be controlled withhold therapy and evaluate; assess benefit/risk when considering whether to restart therapy; monitor blood pressure regularly in all patients receiving therapy
    • Patients with New York Heart Association Class III and IV heart failure, MI in the preceding 6 months, and conduction abnormalities uncontrolled by medications were not eligible for the clinical trials; these patients may be at greater risk for cardiac complications

Pregnancy and Lactation

  • Can cause fetal harm based on findings from animal studies and the drug’s mechanism of action
  • Conduct pregnancy testing on females of reproductive potential before initiating treatment
  • Females of reproductive potential should be advised to avoid becoming pregnant while being treated
  • Males of reproductive potential should be advised to avoid fathering a child while being treated
  • Based on the mechanism of action, therapy may affect either male or female fertility; there are no data on the effect of drugs on human fertility
  • Contraception
    • Advise females of reproductive potential to use contraception during treatment and for 6 months following the final dose; if the drug is used during pregnancy or if the patient becomes pregnant during treatment, the patient should be apprised of the potential risk to the fetus
    • Advise male patients with female sexual partners to use effective contraceptive measures or abstain from sexual activity to prevent pregnancy during treatment and for at least 90 days following completion of therapy
  • Lactation
    • There are no data on the presence of the drug in human milk, effects on the breastfed children, or milk production; because many drugs are excreted in human milk and the potential for serious adverse reactions in breastfed child unknown, advise nursing women not to breastfeed during treatment and for 2 weeks after treatment
References
Mesdcape. Carfilzomib.

https://reference.medscape.com/drug/kyprolis-carfilzomib-999762#6

Health Solutions From Our Sponsors