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  • Kyprolis
    / Amgen


    Active Ingredient
    Carfilzomib 60 mg/vial

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Vial

    1 X 60 mg

    partial basket chart 50848 11251

    Related information


    Dosage

    Administration Precautions
    Hydration: Adequate hydration is required prior to dosing in Cycle 1, especially in patients at high-risk of tumor lysis syndrome (TLS) 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 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.
    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 during Cycle 1 to reduce the incidence and severity of infusion reactions. Reinstate dexamethasone premedication if these symptoms occur during subsequent cycles.
    Administration: Kyprolis can be administered in a 50 mL or 100 mL intravenous bag of 5% Dextrose Injection, USP. Infuse over 10 or 30 minutes depending on the Kyprolis dose regimen. Administer as an intravenous infusion. 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.
    Dose Calculation: Calculate the Kyprolis dose using the patient’s actual body surface area (BSA) at baseline. In patients with a BSA greater than 2.2 m², calculate the dose based upon a BSA of 2.2 m².
    Thromboprophylaxis: 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.
    Infection Prophylaxis: Consider antiviral prophylaxis for patients being treated with Kyprolis to decrease the risk of herpes zoster reactivation.
    Patients on Hemodialysis: Administer Kyprolis after the hemodialysis procedure.
    Recommended Dosing
    Kyprolis in Combination with Dexamethasone: For the combination regimen with dexamethasone alone, administer Kyprolis intravenously once weekly or twice weekly as a 30-minute infusion as described in Table 1 & 2 at the attached doctor’s leaflet.
    Once weekly 20/70 mg/m² regimen by 30-minute infusion: Kyprolis is administered intravenously as a 30-minute infusion once weekly for three weeks followed by a 13-day rest period as shown in Table 1. Each 28-day period is considered one treatment cycle. Administer Kyprolis at a starting dose of 20 mg/m² in Cycle 1 on Day 1. If tolerated, escalate the dose to 70 mg/m² on Day 8 of Cycle 1. Dexamethasone 40 mg is taken by mouth or intravenously on Days 1, 8, and 15 of all cycles and on Day 22 of Cycles 1 to 9. Administer dexamethasone 30 minutes to 4 hours before Kyprolis.
    Treatment may be continued until disease progression or unacceptable toxicity occurs. Refer to the dexamethasone Prescribing Information for other information on that product.
    Twice weekly 20/56 mg/m² regimen by 30-minute infusion: Kyprolis is administered 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 at the attached doctor’s leaflet. Each 28-day period is considered one treatment cycle. Administer Kyprolis 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.
    Treatment may be continued until disease progression or unacceptable toxicity occurs. Refer to the dexamethasone Prescribing Information for other information on that product.
    Kyprolis in Combination with Lenalidomide and Dexamethasone: For the combination regimen with lenalidomide and dexamethasone, administer Kyprolis 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 3 at the attached doctor’s leaflet. Each 28-day period is considered one treatment cycle. The recommended starting dose of Kyprolis 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. Discontinue Kyprolis 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 Monotherapy: For monotherapy, administer Kyprolis intravenously as a 10-minute infusion. In Cycles 1 through 12, administer Kyprolis on two consecutive days, each week for three weeks followed by a 12-day rest period as shown in Table 4 at the attached doctor’s leaflet. Each 28-day period is considered one treatment cycle. From Cycle 13, omit the Day 8 and 9 doses of Kyprolis (see Table 4). Premedicate with dexamethasone 4 mg orally or intravenously 30 minutes to 4 hours before each Kyprolis dose in Cycle 1, then as needed to help prevent infusion reactions. The recommended starting dose of Kyprolis 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.
    Dose Modifications Based on Toxicities: Modify dosing based on toxicity. Recommended actions and dose modifications for Kyprolis are presented in Table 5 at the attached doctor’s leaflet. Dose level reductions are presented in Table 6. See the lenalidomide and dexamethasone Prescribing Information respectively for dosing recommendations.
    Dosing in Patients with End Stage Renal Disease: For patients with end stage renal disease who are on hemodialysis, administer Kyprolis after the hemodialysis procedure.
    See prescribing information for full details.


    Indications

    Relapsed or Refractory Multiple Myeloma:
    – 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 prior lines of therapy.
    – as a single agent for the treatment of patients with multiple myeloma who have received at least two prior therapies including bortezomib and an immunomodulatory agent and have demonstrated disease progression on or within 60 days of completion of the last therapy. Approval is based on response rate. Clinical benefit, such as improvement in survival or symptoms, has not been verified.


    Contra-Indications

    Hypersensitivity to the active substance or to any of the excipients.


    Special Precautions

    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. In clinical studies with Kyprolis, these events occurred throughout the course of Kyprolis therapy. Death due to cardiac arrest has occurred within one day of Kyprolis administration. In randomized, open-label, multicenter trials for combination therapies, the incidence of cardiac failure events was 8%.
    Acute Renal Failure: Cases of acute renal failure have occurred in patients receiving Kyprolis. Some of these events have been fatal. Renal insufficiency adverse events (including renal failure) have occurred in approximately 11% of patients treated with Kyprolis. 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 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.
    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 approximately 1% of patients receiving Kyprolis. Some events have been fatal. In the event of drug-induced pulmonary toxicity, discontinue Kyprolis.
    Hemorrhage: Fatal or serious cases of hemorrhage have been reported in patients treated with Kyprolis. Hemorrhagic events have included gastrointestinal, pulmonary, and intracranial hemorrhage and epistaxis.
    Embryo-Fetal Toxicity: Based on the mechanism of action and findings in animals, Kyprolis can cause fetal harm when administered to a pregnant woman.
    See prescribing information for full details.


    Side Effects

    Most commonly reported adverse reactions (incidence ≥ 20%) with Kyprolis Monotherapy are: fatigue, anemia, nausea, thrombocytopenia, dyspnea, diarrhea and pyrexia.
    See prescribing information for full details.


    Drug interactions

    Carfilzomib is primarily metabolized via peptidase and epoxide hydrolase activities, and as a result, the pharmacokinetic profile of carfilzomib is unlikely to be affected by concomitant administration of cytochrome P450 inhibitors and inducers. Carfilzomib is not expected to influence exposure of other drugs.
    Cytochrome P450: In an in vitro study using human liver microsomes, carfilzomib showed modest direct (Ki = 1.7 micromolar) and time-dependent inhibition (Ki = 11 micromolar) of human cytochrome CYP3A4/5. In vitro studies indicated that carfilzomib did not induce human CYP1A2 and CYP3A4 in cultured fresh human hepatocytes. Cytochrome P450-mediated mechanisms play a minor role in the overall metabolism of carfilzomib. A clinical trial of 17 patients using oral midazolam as a CYP3A probe demonstrated that the pharmacokinetics of midazolam were unaffected by concomitant carfilzomib administration.
    Kyprolis is not expected to inhibit CYP3A4/5 activities and/or affect the exposure to CYP3A4/5 substrates.
    P-gp: Carfilzomib is a P-glycoprotein (P-gp) substrate. In vitro, carfilzomib inhibited the efflux transport of P-gp substrate digoxin by 25% in a Caco-2 monolayer system. However, given that Kyprolis is administered intravenously and is extensively metabolized, the pharmacokinetics of Kyprolis is unlikely to be affected by P-gp inhibitors or inducers.


    Pregnancy and Lactation

    Pregnancy: Kyprolis can cause fetal harm based on findings from animal studies and the drug’s mechanism of action. There are no studies with the use of Kyprolis in pregnant women to inform drug-associated risks of adverse developmental outcomes. Advise pregnant women of the potential risk to the fetus.
    Lactation: There are no data on the presence of Kyprolis in human milk, the effects on the breastfed child, or the effects of the drug on milk production. Because many drugs are excreted in human milk and because the potential for serious adverse reactions in a breastfed child from Kyprolis is unknown, advise nursing women not to breastfeed during treatment with Kyprolis and for 2 weeks after treatment.
    See prescribing information for full details.


    Overdose

    Acute onset of chills, hypotension, renal insufficiency, thrombocytopenia, and lymphopenia has been reported following a dose of 200 mg of Kyprolis administered in error.
    There is no known specific antidote for Kyprolis overdosage. In the event of overdose, the patient should be monitored, specifically for the side effects and/or adverse reactions listed in the doctor’s leaflet.


    Manufacturer
    Amgen Europe B.V., Breda, Netherlands.
    Licence holder
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