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  • Ninlaro 2.3 mg, 3 mg, 4 mg
    / Takeda


    Active Ingredient
    Ixazomib (as Citrate) 2.3, 3, 4 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Capsules

    3 X 2.3 mg

    partial basket chart 56187

    Capsules

    3 X 3 mg

    partial basket chart 56196

    Capsules

    3 X 4 mg

    partial basket chart 56222

    Related information


    Dosage

    The recommended starting dose of NINLARO is 4 mg administered orally once a week on Days 1, 8, and 15 of a 28-day treatment cycle. The recommended starting dose of lenalidomide is 25 mg administered on Days 1 through 21 of a 28-day treatment cycle. The recommended starting dose of dexamethasone is 40 mg administered on Days 1, 8, 15, and 22 of a 28-day treatment cycle.
    See prescribing information for full details.
    Concomitant Medications: Consider antiviral prophylaxis in patients being treated with NINLARO to decrease the risk of herpes zoster reactivation.
    See prescribing information for full details.
    Pediatric Use: Safety and effectiveness have not been established in pediatric patients.
    For dose modification guidelines and use in specific populations: See prescribing information for full details.


    Indications

    NINLARO is indicated in combination with lenalidomide and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy.


    Contra-Indications

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


    Special Precautions

    Thrombocytopenia: Thrombocytopenia has been reported with NINLARO with platelet nadirs typically occurring between Days 14-21 of each 28-day cycle and recovery to baseline by the start of the next cycle. Three percent of patients in the NINLARO regimen and 1% of patients in the placebo regimen had a platelet count ≤ 10,000/mm3 during treatment. Less than 1% of patients in both regimens had a platelet count ≤ 5000/mm3 during treatment. Discontinuations due to thrombocytopenia were similar in both regimens (< 1% of patients in the NINLARO regimen and 2% of patients in the placebo regimen discontinued one or more of the three drugs).The rate of platelet transfusions was 6% in the NINLARO regimen and 5% in the placebo regimen. Monitor platelet counts at least monthly during treatment with NINLARO. Consider more frequent monitoring during the first three cycles. Manage thrombocytopenia with dose modifications and platelet transfusions as per standard medical guidelines.
    Gastrointestinal Toxicities: Diarrhea, constipation, nausea, and vomiting, have been reported with NINLARO, occasionally requiring use of antidiarrheal and antiemetic medications, and supportive care. Diarrhea was reported in 42% of patients in the NINLARO regimen and 36% in the placebo regimen, constipation in 34% and 25%, respectively, nausea in 26% and 21%, respectively, and vomiting in 22% and 11%, respectively. Diarrhea resulted in discontinuation of one or more of the three drugs in 1% of patients in the NINLARO regimen and < 1% of patients in the placebo regimen. Adjust dosing for Grade 3 or 4 symptoms.
    Peripheral Neuropathy: The majority of peripheral neuropathy adverse reactions were Grade 1 (18% in the NINLARO regimen and 14% in the placebo regimen) and Grade 2 (8% in the NINLARO regimen and 5% in the placebo regimen). Grade 3 adverse reactions of peripheral neuropathy were reported at 2% in both regimens; there were no Grade 4 or serious adverse reactions.
    The most commonly reported reaction was peripheral sensory neuropathy (19% and 14% in the NINLARO and placebo regimen, respectively). Peripheral motor neuropathy was not commonly reported in either regimen (< 1%). Peripheral neuropathy resulted in discontinuation of one or more of the three drugs in 1% of patients in both regimens. Patients should be monitored for symptoms of neuropathy. Patients experiencing new or worsening peripheral neuropathy may require dose modification.
    Peripheral Edema: Peripheral edema was reported in 25% and 18% of patients in the NINLARO and placebo regimens, respectively. The majority of peripheral edema adverse reactions were Grade 1 (16% in the NINLARO regimen and 13% in the placebo regimen) and Grade 2 (7% in the NINLARO regimen and 4% in the placebo regimen). Grade 3 peripheral edema was reported in 2% and 1% of patients in the NINLARO and placebo regimens, respectively. There was no Grade 4 peripheral edema reported. There were no discontinuations reported due to peripheral edema. Evaluate for underlying causes and provide supportive care, as necessary. Adjust dosing of dexamethasone per its prescribing information or NINLARO for Grade 3 or 4 symptoms.
    Cutaneous Reactions: Rash was reported in 19% of patients in the NINLARO regimen and 11% of patients in the placebo regimen. The majority of the rash adverse reactions were Grade 1 (10% in the NINLARO regimen and 7% in the placebo regimen) or Grade 2 (6% in the NINLARO regimen and 3% in the placebo regimen). Grade 3 rash was reported in 3% of patients in the NINLARO regimen and 1% of patients in the placebo regimen. There were no Grade 4 or serious adverse reactions of rash reported. The most common type of rash reported in both regimens included maculo-papular and macular rash. Rash resulted in discontinuation of one or more of the three drugs in < 1% of patients in both regimens. Manage rash with supportive care or with dose modification if Grade 2 or higher.
    Thrombotic Microangiopathy: Cases, sometimes fatal, of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), have been reported in patients who received NINLARO.
    Monitor for signs and symptoms of TTP/HUS. If the diagnosis is suspected, stop NINLARO and evaluate.
    If the diagnosis of TTP/HUS is excluded, consider restarting NINLARO. The safety of reinitiating NINLARO therapy in patients previously experiencing TTP/HUS is not known.
    Hepatotoxicity: Drug-induced liver injury, hepatocellular injury, hepatic steatosis, hepatitis cholestatic and hepatotoxicity have each been reported in < 1% of patients treated with NINLARO. Events of liver impairment have been reported (6% in the NINLARO regimen and 5% in the placebo regimen). Monitor hepatic enzymes regularly and adjust dosing for Grade 3 or 4 symptoms.
    Embryo-Fetal Toxicity: NINLARO can cause fetal harm when administered to a pregnant woman based on the mechanism of action and findings in animals. There are no adequate and well-controlled studies in pregnant women using NINLARO. Ixazomib caused embryo-fetal toxicity in pregnant rats and rabbits at doses resulting in exposures that were slightly higher than those observed in patients receiving the recommended dose. Females of reproductive potential should be advised to avoid becoming pregnant while being treated with NINLARO. If NINLARO is used during pregnancy or if the patient becomes pregnant while taking NINLARO, the patient should be apprised of the potential hazard to the fetus. Advise females of reproductive potential that they must use effective contraception during treatment with NINLARO and for 90 days following the final dose. Women using hormonal contraceptives should also use a barrier method of contraception.
    See prescribing information for full details.


    Side Effects

    See special precautions for serious adverse reactions. The most frequently reported adverse reactions include diarrhea, constipation, thrombocytopenia, peripheral neuropathy, nausea, peripheral edema, vomiting, back pain, rash, upper respiratory tract infection and ocular diseases.
    See prescribing information for full details.


    Drug interactions

    Avoid concomitant administration of  NINLARO with strong CYP3A inducers (such as rifampin, phenytoin, carbamazepine, and St. John’s Wort).
    See prescribing information for full details.


    Pregnancy and Lactation

    Pregnancy: Male and female patients of childbearing potential must use effective contraceptive measures during and for 90 days following treatment. Dexamethasone is known to be a weak to moderate inducer of CYP3A4 as well as other enzymes and transporters. Because NINLARO is administered with dexamethasone, the risk for reduced efficacy of contraceptives needs to be considered. Advise women using hormonal contraceptives to also use a barrier method of contraception. Based on its mechanism of action and data from animal reproduction studies, NINLARO can cause fetal harm when administered to a pregnant woman. There are no human data available regarding the potential effect of NINLARO on pregnancy or development of the embryo or fetus.
    Lactation: No data are available regarding the presence of NINLARO or its metabolites in human milk, the effects of the drug on the breast fed infant, or the effects of the drug on milk production. Because the potential for serious adverse reactions from NINLARO in breastfed infants is unknown, advise nursing women not to breastfeed during treatment with NINLARO and for 90 days after the last dose.
    See prescribing information for full details.


    Overdose

    There is no known specific antidote for NINLARO overdose. In the event of an overdose, monitor the patient for adverse reactions and provide appropriate supportive care.


    Important notes

    Before/after meal: The drug should be administered at least one hour before or at least two hours after food.
    Handling: NINLARO is a cytotoxic drug. NINLARO should be taken once a week on the same day and at approximately the same time for the first three weeks of a four week cycle. The whole capsule should be swallowed with water. The capsule should not be crushed, chewed or opened. Avoid direct contact with the capsule contents. In case of capsule breakage, avoid direct contact of capsule contents with the skin or eyes. If contact occurs with the skin, wash thoroughly with soap and water. If contact occurs with the eyes, flush thoroughly with water.
    Storage: Do not store above 30°C. Do not freeze. Store capsules in original packaging until immediately prior to use.


    Manufacturer
    Takeda Pharma A/S, Denmark
    Licence holder
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