Indications
  • KYPROLIS® (carfilzomib) is indicated in combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.
  • KYPROLIS® is indicated as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.
  • ... Read More 

PLEASE SEE THE IMPORTANT SAFETY INFORMATION IN THE SECTION BELOW.

COLLAPSE

IMPORTANT SAFETY INFORMATION

Warning: Skin rash

In clinical studies, nearly all patients (90%) taking Vectibix® experienced skin rash or other skin reactions. Severe or life-threatening skin reactions have been reported.

Skin reactions included (but were not limited to):

  • Acne-like rash
  • Skin rash
  • Nail infections
  • Dry skin
  • Redness
  • Skin peeling
  • Openings in the skin
  • Itching

percent of these patients had severe skin reactions, which involved pain, disfigurement, ulceration, or loss of outer layers of skin. Some patients who developed severe skin reactions also developed infections in the blood, skin, fat, or tissue that sometimes resulted in death.

doctor may decrease your dose, delay your next dose, or stop Vectibix® treatment altogether to manage your side effects. It is important that you tell your doctor right away if you have any skin reactions or any signs of infection (such as chills, fever, or increased redness or swelling of an existing skin reaction).


RAS-Mutant mCRC

with RAS-mutant mCRC should not take Vectibix®. Investigations of the clinical studies that used Vectibix® showed that Vectibix® exposed patients with RAS-mutant mCRC to serious side effects without working to treat cancer.


Low Electrolytes

patients who were taking Vectibix® developed low levels of certain electrolytes, including:

  • Magnesium
  • Calcium
  • Potassium

doctor may check the levels of these electrolytes in your blood while you are on treatment and for 2 months after you finish treatment. Your doctor may add other oral or intravenous medications to your Vectibix® treatment.


Infusion Reactions

Vectibix® is given by infusion into a vein. Some patients may develop an infusion reaction, which can be severe and in rare cases has resulted in death. Infusion reactions developed in 4% of patients in one clinical trial, and 1% of patients experienced serious infusion reactions. Infusion reactions included:

  • Fever
  • Shortness of breath
  • Low blood pressure
  • Chills
  • Throat spasms

on how severe the reaction is, your doctor may decide to slow the rate of the infusion, stop the infusion, or stop your Vectibix® treatment completely.


Kidney problems

Tell your doctor right away if you experience severe diarrhea or dehydration. Some patients treated with Vectibix® and chemotherapy developed kidney failure or other complications because of severe diarrhea and dehydration.

Lung problems

Lung disease, including fatal lung disease, occurred in 1% or less of patients who had taken Vectibix®. Tell your doctor if you have problems breathing, wheezing, or a cough that doesn’t go away or keeps coming back. If you have been told that you have had lung problems in the past, be sure to tell your doctor. Your doctor may decide to stop Vectibix® treatment.

Avoid sunlight

Being in the sun may make skin reactions worse. Wear sunscreen and protective clothing (like a hat), and avoid direct sunlight while you are on treatment with Vectibix®. Tell your doctor if you have new or worsening skin reactions.


Eye problems

Inflammation of the eye and injury to the cornea have been reported. Tell your doctor if you have any vision changes or eye problems.


Do not take with Avastin®

Patients treated with Avastin® (bevacizumab) and Vectibix® together did not live as long and had more serious side effects, such as acne-like rash, diarrhea, dehydration, painful ulcers and mouth sores, and low levels of potassium and magnesium in the blood. Some patients developed blood clots that can travel to the lungs, which can be very serious or even fatal. Do not take Avastin® with Vectibix®.


Avoid pregnancy

Use effective birth control to avoid pregnancy while taking Vectibix® and for 6 months after the last dose. It is possible for a pregnant patient to transfer Vectibix® to an unborn child, which could be harmful to the unborn child.


Avoid breastfeeding

Vectibix® could also be transferred to a child through breast milk. Your doctor may tell you that you should not nurse your baby during Vectibix® therapy and for 2 months after your last dose of Vectibix®.


Pregnancy Surveillance Program

Women who become pregnant during Vectibix® treatment are encouraged to enroll in Amgen’s Pregnancy Surveillance Program. Women who are nursing during Vectibix® treatment are encouraged to enroll in Amgen’s Lactation Surveillance Program. Call 1 (800) 772-6436 to enroll.


Most common side effects

In clinical studies using Vectibix® alone, the most common side effects were severe skin reactions, nail infections, lack of energy, nausea, and diarrhea. The most common serious side effects were general declining health and blockage of the bowel.

In clinical studies using Vectibix® with FOLFOX, the most commonly reported side effects for wild-type KRAS patients were diarrhea, painful mouth swelling, swelling/redness of the inner lining of the mouth, lack of energy, nail infection, lack of hunger, unusual magnesium and potassium levels in the blood, rash, acne-like rash, severe itching, and dry skin. The most serious side effects reported in Vectibix®-treated wild-type KRAS patients were diarrhea and dehydration.


Talk to your doctor

Tell your doctor right away if you have any side effects such as worsening skin problems, eye problems, fever, chills, breathing problems (such as a cough that doesn’t go away or keeps coming back, wheezing, or shortness of breath), if you develop diarrhea or become dehydrated, or if you become pregnant.


Other medications

Do not change or stop any medications you may be taking (including over-the-counter drugs or supplements you can buy without a prescription) without first speaking with your doctor.

Please read the full Prescribing Information and discuss it with your doctor.

Dosing and administration

Reconstitution and preparation

Follow these steps to reconstitute and prepare KYPROLIS®

Step 1

Calculate the dose (mg/m2) and number of vials of KYPROLIS® required using the patient’s body surface area (BSA) at baseline. Patients with a BSA greater than 2.2 m2 should receive a dose based upon a BSA of 2.2 m2. Dose adjustments do not need to be made for weight changes of less than or equal to 20%.1

Step 2

Remove vial from refrigerator just prior to use.1

Step 3

Use a 21-gauge or larger gauge needle (0.8 mm or smaller external diameter needle) to aseptically reconstitute each vial by slowly injecting 29 mL (for 60 mg vial) or 15 mL (for 30 mg vial) Sterile Water for Injection, USP, through the stopper and directing the solution onto the INSIDE WALL OF THE VIAL to minimize foaming.1

Step 4

Gently swirl and/or invert the vial slowly for about 1 minute, or until complete dissolution. DO NOT SHAKE to avoid foam generation. If foaming occurs, allow the solution to settle in the vial until foaming subsides (approximately 5 minutes) and the solution is clear.1

Step 5

Visually inspect for particulate matter and discoloration prior to administration. The reconstituted product should be a clear, colorless solution and should not be administered if any discoloration or particulate matter is observed.1

Step 6

Discard any unused portion left in the vial. DO NOT pool unused portions from the vials. DO NOT administer more than one dose from a vial.1

Step 7

Optionally, KYPROLIS® can be administered in an intravenous bag.1

Step 8

When administering in an intravenous bag, use a 21-gauge or larger gauge needle (0.8 mm or smaller external diameter needle) to withdraw the calculated dose from the vial and dilute into 50 mL or 100 mL intravenous bag containing 5% Dextrose Injection, USP (based on the calculated total dose and infusion time).1

KYPROLIS® Dosing and Administration: Reconstitution and PreparationKYPROLIS® Dosing and Administration: Reconstitution and Preparation

Read the complete preparation instructions prior to reconstitution. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.1

Precautions for administration of KYPROLIS®1

The quantity of KYPROLIS® (carfilzomib) contained in one single-dose vial (30 mg or 60 mg) may exceed the recommended dose. Caution should be used in calculating the quantity delivered to prevent overdosing.

  • KYPROLIS® 56 mg/m2 is infused intravenously over 30 minutes
  • KYPROLIS® 27 mg/m2 is infused intravenously for 10 minutes

Do not administer as a bolus. Flush the intravenous administration line with normal saline or 5% dextrose injection, USP, immediately before and after KYPROLIS® administration. Do not mix KYPROLIS® with or administer as an infusion with other medicinal products.

Storage1

KYPROLIS® vials contain no antimicrobial preservatives and are intended for single use only. Unopened vials of KYPROLIS® are stable until the date indicated on the package when stored in the original package at 2°C to 8°C (36°F to 46°F). The reconstituted solution contains carfilzomib at a concentration of 2 mg/mL.

Storage conditions of reconstituted KYPROLIS® Stability per container*
Vial Syringe Intravenous bag (D5W)
Refrigerated (2°C to 8°C; 36°F to 46°F) 24 hours 24 hours 24 hours
Room temperature (15°C to 30°C; 59°F to 86°F) 4 hours 4 hours 4 hours

Additional dosing considerations

Hydration management1
Additional dosing considerations: Hydration management

Adequate hydration is required prior to dosing in Cycle 1, especially in patients at high risk of tumor lysis syndrome or renal toxicity.

  • The recommended hydration includes both oral fluids (30 mL per kg at least 48 hours before Cycle 1, Day 1) and IV fluids (250 mL to 500 mL of appropriate IV fluid prior to each dose in Cycle 1)
  • If needed, give an additional 250 mL to 500 mL of intravenous fluids following KYPROLIS® administration
  • Continue oral and/or intravenous hydration, as needed, in subsequent cycles
  • Monitor patients for evidence of volume overload and adjust hydration to individual patient needs, especially in patients with or at risk for cardiac failure

Hydration requirements for KYPROLIS® prior to Cycle 11

Adequate hydration is required prior to dosing in Cycle 1, especially in patients at high risk of tumor lysis syndrome (TLS).

  • Cases of TLS, including fatal outcomes, have been reported in patients who received KYPROLIS®
  • Patients with multiple myeloma and a high tumor burden should be considered to be at greater risk for TLS
  • Ensure that patients are well hydrated before administration of KYPROLIS® in Cycle 1, and in subsequent cycles as needed
  • Uric acid lowering drugs should be considered in patients at risk for TLS
  • Monitor for evidence of TLS during treatment and manage promptly
  • Interrupt KYPROLIS® until TLS is resolved

Infusion reactions1

  • Infusion reactions, including life‑threatening reactions, have been reported in patients who received KYPROLIS®
  • Symptoms include fever, chills, arthralgia, myalgia, facial flushing, facial edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina
  • These reactions can occur immediately following or up to 24 hours after administration of KYPROLIS®. Administer dexamethasone prior to KYPROLIS® to reduce the incidence and severity of infusion reactions
  • Inform patients of the risk and symptoms and to contact a physician immediately if symptoms of an infusion reaction occur
Premedications and concomitant medications1
Additional dosing considerations: premedications and concomitant medications
  • Premedicate with the recommended dose of dexamethasone for monotherapy or the recommended dexamethasone dose if on combination therapy. Administer dexamethasone orally or intravenously at least 30 minutes but no more than 4 hours prior to all doses of KYPROLIS® during Cycle 1 to reduce the incidence and severity of infusion reactions. Reinstate dexamethasone premedication if these symptoms occur during subsequent cycles
  • Consider antiviral prophylaxis for patients being treated with KYPROLIS® to decrease the risk of herpes zoster reactivation
  • Advise patients to discuss any medication they are currently taking prior to starting treatment with KYPROLIS®, or prior to starting any new medication(s) during treatment with KYPROLIS®
  • Thromboprophylaxis is recommended for patients being treated with the combination of KYPROLIS® with dexamethasone or with lenalidomide plus dexamethasone. The thromboprophylaxis regimen should be based on an assessment of the patient’s underlying risks
  • Refer to the dexamethasone Prescribing Information for other concomitant medications. If treating with lenalidomide, refer to that Prescribing Information for other concomitant medications

Dose modifications

Dose modifications for toxicity during KYPROLIS® treatment1
Hematologic toxicity Recommended action
  • Absolute neutrophil count (ANC) less than 0.5 x 109/L
  • Withhold dose
    • If recovered to greater than or equal to 0.5 x 109/L, continue at the same dose level
  • For subsequent drops to less than 0.5 x 109/L, follow the same recommendations as above and consider 1 dose level reduction when restarting KYPROLIS®*
  • Febrile neutropenia (ANC less than 0.5 x 109/L and an oral temperature more than 38.5°C or two consecutive readings of more than 38.0°C for 2 hours)
  • Withhold dose
    • If ANC returns to baseline grade and fever resolves, resume at the same dose level
  • Platelets less than 10 x 109/L or evidence of bleeding with thrombocytopenia
  • Withhold dose
    • If recovered to greater than or equal to 10 x 109/L and/or bleeding is controlled, continue at the same dose level
  • For subsequent drops to less than 10 x 109/L, follow the same recommendations as above and consider 1 dose level reduction when restarting KYPROLIS®*
Renal toxicity Recommended action
  • Serum creatinine greater than or equal to 2 × baseline, or
  • Creatinine clearance less than 15 mL/min, or creatinine clearance decreases to less than or equal to 50% of baseline, or need for hemodialysis
  • Withhold dose and continue monitoring renal function (serum creatinine or creatinine clearance)
    • If attributable to KYPROLIS®, resume when renal function has recovered to within 25% of baseline; start at 1 dose level reduction*
  • If not attributable to KYPROLIS®, dosing may be resumed at the discretion of the physician
  • For patients on hemodialysis receiving KYPROLIS®, the dose is to be administered after the hemodialysis procedure
Other non-hematologic toxicity Recommended action
  • All other severe or life-threatening (CTCAE Grade 3 or 4) non-hematological toxicities
  • Withhold until resolved or returned to baseline
  • Consider restarting the next scheduled treatment at 1 dose level reduction (see table below for dose level reductions)

CTCAE = Common Terminology Criteria for Adverse Events.

Dose modifications for use in hepatic impairment1

For patients with mild or moderate hepatic impairment, reduce the dose of KYPROLIS® by 25%. Dosing recommendation cannot be made in patients with severe hepatic impairment.

Dosing in patients with end stage renal disease1

For patients with end stage renal disease who are on dialysis, administer KYPROLIS® after the hemodialysis procedure.

Dose level reductions for KYPROLIS®1
Regimen Dose First dose reduction Second dose reduction Third dose reduction
KYPROLIS®, lenalid-
omide, and dexa-
methasone, or mono-
therapy (20/27 mg/m2)
27 mg/m2 20 mg/m2 15 mg/m2
KYPROLIS® and dexa-
methasone, or mono-
therapy (20/56 mg/m2)
56 mg/m2 45 mg/m2 36 mg/m2 27 mg/m2,*

Note: Infusion times remain unchanged during dose reduction(s).

REFERENCES

1. KYPROLIS® (carfilzomib) prescribing information, Onyx Pharmaceuticals Inc., an Amgen Inc. subsidiary.

IMPORTANT SAFETY INFORMATION

Cardiac Toxicities

  • New onset or worsening of pre-existing cardiac failure (e.g., congestive heart failure, pulmonary edema, decreased ejection fraction), restrictive cardiomyopathy, myocardial ischemia, and myocardial infarction including fatalities have occurred following administration of KYPROLIS. Some events occurred in patients with normal baseline ventricular function. Death due to cardiac arrest has occurred within one day of KYPROLIS administration.
  • Monitor patients for clinical signs or symptoms of cardiac failure or cardiac ischemia. Evaluate promptly if cardiac toxicity is suspected. Withhold KYPROLIS for Grade 3 or 4 cardiac adverse events until recovery, and consider whether to restart KYPROLIS at 1 dose level reduction based on a benefit/risk assessment.
  • While adequate hydration is required prior to 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.
  • Patients ≥ 75 years, the risk of cardiac failure is increased. Patients with New York Heart Association Class III and IV heart failure, recent myocardial infarction, conduction abnormalities, angina, or arrhythmias may be at greater risk for cardiac complications and should have a comprehensive medical assessment (including blood pressure control and fluid management) prior to starting treatment with KYPROLIS and remain under close follow-up.

Acute Renal Failure

  • Cases of acute renal failure, including some fatal renal failure events, and renal insufficiency adverse events (including renal failure) have occurred in patients receiving KYPROLIS. Acute renal failure was reported more frequently in patients with advanced relapsed and refractory multiple myeloma who received KYPROLIS monotherapy. Monitor renal function with regular measurement of the serum creatinine and/or estimated creatinine clearance. Reduce or withhold dose as appropriate.

Tumor Lysis Syndrome

  • Cases of Tumor Lysis Syndrome (TLS), including fatal outcomes, have occurred in patients receiving KYPROLIS. Patients with multiple myeloma and a high tumor burden should be considered at greater risk for TLS. Adequate hydration is required prior to each dose in Cycle 1, and in subsequent cycles as needed. Consider uric acid lowering drugs in patients at risk for TLS. Monitor for evidence of TLS during treatment and manage promptly. Withhold KYPROLIS until TLS is resolved.

Pulmonary Toxicity

  • Acute Respiratory Distress Syndrome (ARDS), acute respiratory failure, and acute diffuse infiltrative pulmonary disease such as pneumonitis and interstitial lung disease have occurred in patients receiving KYPROLIS. Some events have been fatal. In the event of drug‐induced pulmonary toxicity, discontinue KYPROLIS.

Pulmonary Hypertension

  • Pulmonary arterial hypertension (PAH) was reported in patients treated with KYPROLIS. Evaluate with cardiac imaging and/or other tests as indicated. Withhold KYPROLIS for PAH until resolved or returned to baseline and consider whether to restart KYPROLIS based on a benefit/risk assessment.

Dyspnea

  • Dyspnea was reported in patients treated with KYPROLIS. Evaluate dyspnea to exclude cardiopulmonary conditions including cardiac failure and pulmonary syndromes. Stop KYPROLIS for Grade 3 or 4 dyspnea until resolved or returned to baseline. Consider whether to restart KYPROLIS based on a benefit/risk assessment.

Hypertension

  • Hypertension, including hypertensive crisis and hypertensive emergency, has been observed with KYPROLIS. Some of these events have been fatal. It is recommended to control hypertension prior to starting KYPROLIS. Monitor blood pressure regularly in all patients. If hypertension cannot be adequately controlled, withhold KYPROLIS and evaluate. Consider whether to restart KYPROLIS based on a benefit/risk assessment.

Venous Thrombosis

  • Venous thromboembolic events (including deep venous thrombosis and pulmonary embolism) have been observed with KYPROLIS. Thromboprophylaxis is recommended for patients being treated with the combination of KYPROLIS with dexamethasone or with lenalidomide plus dexamethasone. The thromboprophylaxis regimen should be based on an assessment of the patient’s underlying risks.
  • 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 KYPROLIS in combination with dexamethasone or lenalidomide plus dexamethasone.

Infusion Reactions

  • Infusion reactions, including life-threatening reactions, have occurred in patients receiving KYPROLIS. Symptoms include fever, chills, arthralgia, myalgia, facial flushing, facial edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina. These reactions can occur immediately following or up to 24 hours after administration of KYPROLIS. Premedicate with dexamethasone to reduce the incidence and severity of infusion reactions. Inform patients of the risk and of symptoms of an infusion reaction and to contact a physician immediately if they occur.

Hemorrhage

  • Fatal or serious cases of hemorrhage have been reported in patients receiving KYPROLIS. Hemorrhagic events have included gastrointestinal, pulmonary, and intracranial hemorrhage and epistaxis. Promptly evaluate signs and symptoms of blood loss. Reduce or withhold dose as appropriate.

Thrombocytopenia

  • KYPROLIS causes thrombocytopenia with recovery to baseline platelet count usually by the start of the next cycle. Thrombocytopenia was reported in patients receiving KYPROLIS. Monitor platelet counts frequently during treatment with KYPROLIS. Reduce or withhold dose as appropriate.

Hepatic Toxicity and Hepatic Failure

  • Cases of hepatic failure, including fatal cases, have been reported during treatment with KYPROLIS. KYPROLIS can cause increased serum transaminases. Monitor liver enzymes regularly regardless of baseline values. Reduce or withhold dose as appropriate.

Thrombotic Microangiopathy

  • Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), including fatal outcome have occurred in patients receiving KYPROLIS. Monitor for signs and symptoms of TTP/HUS. Discontinue KYPROLIS if diagnosis is suspected. If the diagnosis of TTP/HUS is excluded, KYPROLIS may be restarted. The safety of reinitiating KYPROLIS therapy in patients previously experiencing TTP/HUS is not known.

Posterior Reversible Encephalopathy Syndrome (PRES)

  • Cases of PRES have occurred in patients receiving KYPROLIS. PRES was formerly known as Reversible Posterior Leukoencephalopathy Syndrome. Consider a neuro-radiological imaging (MRI) for onset of visual or neurological symptoms. Discontinue KYPROLIS if PRES is suspected and evaluate. The safety of reinitiating KYPROLIS therapy in patients previously experiencing PRES is not known.

Increased Fatal and Serious Toxicities in Combination with Melphalan and Prednisone in Newly Diagnosed Transplant-ineligible Patients

  • In a clinical trial of transplant-ineligible patients with newly diagnosed multiple myeloma comparing KYPROLIS, melphalan, and prednisone (KMP) vs bortezomib, melphalan, and prednisone (VMP), a higher incidence of serious and fatal adverse events was observed in patients in the KMP arm. KYPROLIS in combination with melphalan and prednisone is not indicated for transplant-ineligible patients with newly diagnosed multiple myeloma.

Embryo-fetal Toxicity

  • KYPROLIS can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals.
  • Females of reproductive potential should be advised to avoid becoming pregnant while being treated with KYPROLIS. Males of reproductive potential should be advised to avoid fathering a child while being treated with KYPROLIS. If this drug is used during pregnancy, or if pregnancy occurs while taking this drug, the patient should be apprised of the potential hazard to the fetus.

ADVERSE REACTIONS

  • The most common adverse reactions occurring in at least 20% of patients treated with KYPROLIS in the combination therapy trials: anemia, neutropenia, diarrhea, dyspnea, fatigue, thrombocytopenia, pyrexia, insomnia, muscle spasm, cough, upper respiratory tract infection, hypokalemia.
  • The most common adverse reactions occurring in at least 20% of patients treated with KYPROLIS in monotherapy trials: anemia, fatigue, thrombocytopenia, nausea, pyrexia, dyspnea, diarrhea, headache, cough, edema peripheral.

Please see full Prescribing Information.

INDICATIONS

  • KYPROLIS® (carfilzomib) is indicated in combination with dexamethasone or with lenalidomide plus dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.
  • KYPROLIS® is indicated as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.