Kyprolis 60mg

Relapsed or Refractory Multiple Myeloma

• ​Kyprolis 60mg 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 60mg 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.

Kyprolis 60mg (Kyprolis 60mg) is a cancer medicine that interferes with the growth and spread of cancer cells in the body.

Kyprolis 60mg is used to treat multiple myeloma. It is sometimes given in conjunction with other medicines when treating relapsed multiple myeloma.

Kyprolis 60mg is usually given after at least two other cancer medicines have been tried without success.

Administration Precautions

• Hydration - 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 intravenous fluids (250 mL to 500 mL of appropriate intravenous fluid prior to each dose in Cycle 1). If needed, give an additional 250 mL to 500 mL of intravenous fluids following Kyprolis 60mg 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.
• Electrolyte Monitoring - Monitor serum potassium levels regularly during treatment with Kyprolis 60mg.
• Premedications - 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 60mg during Cycle 1 to reduce the incidence and severity of infusion reactions. Reinstate dexamethasone premedication if these symptoms occur during subsequent cycles.
• Administration - Infuse over 10 or 30 minutes depending on the Kyprolis 60mg dose regimen. Do not administer as a bolus. Flush the intravenous administration line with normal saline or 5% dextrose injection, USP immediately before and after Kyprolis 60mg administration. Do not mix Kyprolis 60mg with or administer as an infusion with other medicinal products.
• Dose Calculation - Calculate the Kyprolis 60mg dose using the patient's actual body surface area at baseline. In patients with a body surface area greater than 2.2 m2, calculate the dose based upon a body surface area of 2.2 m2.
• Thromboprophylaxis - Thromboprophylaxis is recommended for patients being treated with the combination of Kyprolis 60mg with dexamethasone or with lenalidomide plus dexamethasone. The thromboprophylaxis regimen should be based on an assessment of the patient's underlying risks.
• Infection Prophylaxis - Consider antiviral prophylaxis for patients being treated with Kyprolis 60mg to decrease the risk of herpes zoster reactivation.

Recommended Dosing

Kyprolis 60mg in Combination with Lenalidomide and Dexamethasone

For the combination regimen with lenalidomide and dexamethasone, administer Kyprolis 60mg intravenously as a 10-minute infusion on two consecutive days, each week for three weeks followed by a 12-day rest period as shown in Table 1. Each 28-day period is considered one treatment cycle. The recommended starting dose of Kyprolis 60mg is 20 mg/m2 in Cycle 1 on Days 1 and 2. If tolerated, escalate the dose to 27 mg/m2 on Day 8 of Cycle 1. From Cycle 13, omit the Day 8 and 9 doses of Kyprolis 60mg. Discontinue Kyprolis 60mg after Cycle 18. Lenalidomide 25 mg is taken orally on Days 1–21 and dexamethasone 40 mg by mouth or intravenously on Days 1, 8, 15, and 22 of the 28-day cycles.

Continue treatment until disease progression or unacceptable toxicity occurs. Refer to the lenalidomide and dexamethasone Prescribing Information for other concomitant medications, such as the use of anticoagulant and antacid prophylaxis, that may be required with those agents.

​Kyprolis 60mg in Combination with Dexamethasone

​For the combination regimen with dexamethasone, administer Kyprolis 60mg intravenously as a 30-minute infusion on two consecutive days, each week for three weeks followed by a 12-day rest period as shown in Table 2. Each 28-day period is considered one treatment cycle. Administer Kyprolis 60mg by 30-minute infusion at a starting dose of 20 mg/m2 in Cycle 1 on Days 1 and 2. If tolerated, escalate the dose to 56 mg/m2 on Day 8 of Cycle 1. Dexamethasone 20 mg is taken by mouth or intravenously on Days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. Administer dexamethasone 30 minutes to 4 hours before Kyprolis 60mg.

​Treatment may be continued until disease progression or unacceptable toxicity occurs. Refer to the dexamethasone Prescribing Information for other concomitant medications.

​Kyprolis 60mg Monotherapy

​For monotherapy, administer Kyprolis 60mg intravenously as a 10-minute or 30-minute infusion depending on the regimen as described below.

20/27 mg/m2 regimen by 10-minute infusion

For monotherapy using the 20/27 mg/m2 regimen, administer Kyprolis 60mg intravenously as a 10-minute infusion. In Cycles 1 through 12, administer Kyprolis 60mg on two consecutive days, each week for three weeks followed by a 12-day rest period as shown in Table 3. Each 28-day period is considered one treatment cycle. From Cycle 13, omit the Day 8 and 9 doses of Kyprolis 60mg. Premedicate with dexamethasone 4 mg orally or intravenously 30 minutes to 4 hours before each Kyprolis 60mg dose in Cycle 1, then as needed to help prevent infusion reactions. The recommended starting dose of Kyprolis 60mg is 20 mg/m2 in Cycle 1 on Days 1 and 2. If tolerated, escalate the dose to 27 mg/m2 on Day 8 of Cycle 1. Treatment may continue until disease progression or unacceptable toxicity occurs.

​20/56 mg/m2 regimen by 30-minute infusion

​For monotherapy using the 20/56 mg/m2 regimen, administer Kyprolis 60mg intravenously as a 30-minute infusion. In Cycles 1 through 12, administer Kyprolis 60mg on two consecutive days, each week for three weeks followed by a 12-day rest period as shown in Table 4. Each 28-day period is considered one treatment cycle. From Cycle 13, omit the Day 8 and 9 doses of Kyprolis 60mg. Premedicate with dexamethasone 8 mg orally or intravenously 30 minutes to 4 hours before each Kyprolis 60mg dose in Cycle 1, then as needed to help prevent infusion reactions. The recommended starting dose of Kyprolis 60mg is 20 mg/m2 in Cycle 1 on Days 1 and 2. If tolerated, escalate the dose to 56 mg/m2 on Day 8 of Cycle 1. Treatment may continue until disease progression or unacceptable toxicity occurs.

Dose Modifications Based on Toxicities

Modify dosing based on toxicity. Recommended actions and dose modifications for Kyprolis 60mg are presented in Table 5. Dose level reductions are presented in Table 6. See the lenalidomide and dexamethasone Prescribing Information respectively for dosing recommendations.

Reconstitution and Preparation for

Intravenous Administration

Kyprolis 60mg vials contain no antimicrobial preservatives and are intended for single use only. Unopened vials of Kyprolis 60mg 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. The quantity of Kyprolis 60mg contained in one single-dose vial (60 mg Kyprolis 60mg) may exceed the required dose. Use caution in calculating the quantity delivered to prevent overdosing. 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.

Reconstitution/Preparation Steps:

1. Remove vial from refrigerator just prior to use.
2. Calculate the dose (mg/m2) and number of vials of Kyprolis 60mg 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%.
3. Aseptically reconstitute each vial by slowly injecting 29 mL Sterile Water for Injection, USP, through the stopper and directing the solution onto the INSIDE WALL OF THE VIAL to minimize foaming.

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.
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.
6. Discard any unused portion left in the vial. DO NOT pool unused portions from the vials.
7. Optionally, Kyprolis 60mg can be administered in an intravenous bag.
8. When administering in an intravenous bag, 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).

The stabilities of reconstituted Kyprolis 60mg under various temperature and container conditions are shown in Table 7.

See also:
What is the most important information I should know about Kyprolis 60mg?

There are no contraindications listed in the manufacturer's US labeling

Canadian labeling: Hypersensitivity to Kyprolis 60mg or any component of the formulation

Use Kyprolis 60mg as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• Kyprolis 60mg is usually given as an injection at your doctor's office, hospital, or clinic. Contact your health care provider if you have any questions.
• Do not use Kyprolis 60mg if it contains particles, is cloudy or discolored, or if the vial is cracked or damaged.
• Drinking extra fluids while you are taking Kyprolis 60mg is recommended. Check with your doctor for instructions.
• Your doctor may prescribe a corticosteroid medicine (eg, dexamethasone) for you to take before you use Kyprolis 60mg. This will help to decrease the risk of an infusion reaction. Discuss any questions or concerns with your doctor.
• Keep this product, as well as syringes and needles, out of the reach of children and away from pets. Do not reuse needles, syringes, or other materials. Ask your health care provider how to dispose of these materials after use. Follow all local rules for disposal.
• It is very important that each dose is given at the scheduled time. If you miss a dose of Kyprolis 60mg, contact your doctor right away to establish a new dosing schedule. Do not use 2 doses at once.

Ask your health care provider any questions you may have about how to use Kyprolis 60mg.

This medication is used to treat a certain type of cancer (multiple myeloma). Kyprolis 60mg can be used alone or along with other medications (such as lenalidomide, dexamethasone). It works by helping to slow the growth and spread of cancer cells.

How to use Kyprolis 60mg intravenous

This medication is given by injection into a vein by a health care professional. It is given as directed by your doctor, usually over 10 minutes or over 30 minutes. The dosage is based on your body size, lab tests, medical condition, and response to treatment.

This medication can sometimes cause a serious reaction during the injection. Tell your doctor right away if you develop symptoms such as chills, fever, flushing, trouble breathing, joint/muscle pain, chest pain, or fainting. Your doctor may prescribe other medications (such as dexamethasone) before each dose to help prevent serious side effects. Carefully follow your doctor's directions.

See also:
What other drugs will affect Kyprolis 60mg?

BCG (Intravesical): Myelosuppressive Agents may diminish the therapeutic effect of BCG (Intravesical). Avoid combination

Chloramphenicol (Ophthalmic): May enhance the adverse/toxic effect of Myelosuppressive Agents. Monitor therapy

Cladribine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Avoid combination

CloZAPine: Myelosuppressive Agents may enhance the adverse/toxic effect of CloZAPine. Specifically, the risk for neutropenia may be increased. Monitor therapy

Deferiprone: Myelosuppressive Agents may enhance the neutropenic effect 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. Consider therapy modification

Dipyrone: May enhance the adverse/toxic effect of Myelosuppressive Agents. Specifically, the risk for agranulocytosis and pancytopenia may be increased Avoid combination

Erdafitinib: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Estrogen Derivatives (Contraceptive): Kyprolis 60mg may enhance the thrombogenic effect of Estrogen Derivatives (Contraceptive). Management: Consider alternative, non-hormonal methods of contraception in patients requiring therapy with Kyprolis 60mg. Consider therapy modification

Lasmiditan: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Avoid combination

Lumacaftor and Ivacaftor: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. Lumacaftor and Ivacaftor may increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Mesalamine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

P-glycoprotein/ABCB1 Inducers: May decrease the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inducers may also further limit the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

P-glycoprotein/ABCB1 Inhibitors: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. P-glycoprotein inhibitors may also enhance the distribution of p-glycoprotein substrates to specific cells/tissues/organs where p-glycoprotein is present in large amounts (e.g., brain, T-lymphocytes, testes, etc.). Monitor therapy

Progestins (Contraceptive): Kyprolis 60mg may enhance the thrombogenic effect of Progestins (Contraceptive). Management: Consider alternative, non-hormonal methods of contraception in patients requiring therapy with Kyprolis 60mg. Consider therapy modification

Promazine: May enhance the myelosuppressive effect of Myelosuppressive Agents. Monitor therapy

Ranolazine: May increase the serum concentration of P-glycoprotein/ABCB1 Substrates. Monitor therapy

Solriamfetol: May enhance the hypertensive effect of Hypertension-Associated Agents. Monitor therapy

See also:
What are the possible side effects of Kyprolis 60mg?

Applies to Kyprolis 60mg: intravenous powder for solution

In addition to its needed effects, some unwanted effects may be caused by Kyprolis 60mg (the active ingredient contained in Kyprolis 60mg). In the event that any of these side effects do occur, they may require medical attention.

If any of the following side effects occur while taking Kyprolis 60mg, check with your doctor or nurse immediately:

More common:

• Agitation
• black, tarry stools
• bleeding gums
• bloating or swelling of the face, arms, hands, lower legs, or feet
• blood in the urine or stools
• burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
• chest pain
• confusion
• cough or hoarseness
• decreased urine output
• depression
• difficult or labored breathing
• difficulty with moving
• dizziness
• drowsiness
• fast or irregular heartbeat
• hostility
• irregular heartbeat
• irritability
• lower back or side pain
• muscle spasms (tetany) or twitching
• nausea or vomiting
• numbness or tingling in the hands, feet, or lips
• painful or difficult urination
• pale skin
• pinpoint red spots on the skin
• seizures
• shortness of breath
• stupor
• swelling of the face, ankles, or hands
• tightness in the chest
• tingling of the hands or feet
• trembling
• troubled breathing with exertion
• ulcers, sores, or white spots in the mouth
• unsteadiness or awkwardness
• unusual bleeding or bruising
• unusual tiredness or weakness
• unusual weight gain or loss
• wheezing

• Chills
• fever
• muscle pain or cramps
• pain in the joints
• painful blisters on the trunk of the body
• weakness in the arms, hands, legs, or feet

Minor Side Effects

Some of the side effects that can occur with Kyprolis 60mg may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common:

• Abdominal or stomach pain
• back pain
• blurred vision
• body aches or pain
• bone pain
• constipation
• diarrhea
• dry mouth
• ear congestion
• flushed, dry skin
• fruit-like breath odor
• headache
• increased hunger
• increased thirst
• increased urination
• loss of appetite
• loss of voice
• metallic taste
• muscle weakness
• pain in the arms or legs
• runny nose
• sneezing
• sore throat
• sweating
• trouble sleeping
• weight loss

Kyprolis 60mg is an injectable antineoplastic agent (IV only). Chemically, it is a modified tetrapeptidyl epoxide and an analog of epoxomicin. It is also a selective proteasome inhibitor. FDA approved on July 20, 2012.