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  • Inlyta
    / Pfizer


    Active Ingredient
    Axitinib 1 mg, 5 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Film Coated Tablets

    60 X 1 mg

    partial basket chart 48746 9684

    Film Coated Tablets

    60 X 5 mg

    partial basket chart 77409 9683

    Related information


    Dosage

    Recommended Dosing: The recommended starting oral dose is 5 mg twice daily. Administer doses approximately 12 hours apart with or without food. The tablets should be swallowed whole with a glass of water.
    If the patient vomits or misses a dose, an additional dose should not be taken. The next prescribed dose should be taken at the usual time.
    Dose Modification Guidelines: Dose increase or reduction is recommended based on individual safety and tolerability.
    Over the course of treatment, patients who tolerate INLYTA for at least two consecutive weeks with no adverse reactions >Grade 2 (according to the Common Toxicity Criteria for Adverse Events [CTCAE]), are normotensive, and are not receiving anti-hypertension medication, may have their dose increased. When a dose increase from 5 mg twice daily is recommended, axitinib dose may be increased to 7 mg twice daily, and further to 10 mg twice daily using the same criteria.
    Over the course of treatment, management of some adverse drug reactions may require temporary interruption or permanent discontinuation and/or dose reduction of axitinib therapy .If dose reduction from 5 mg twice daily is required, the recommended dose is 3 mg twice daily. If additional dose reduction is required, the recommended dose is 2 mg twice daily.
    Strong CYP3A4/5 Inhibitors: The concomitant use of strong CYP3A4/5 inhibitors should be avoided (e.g., ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, and voriconazole). Selection of an alternate concomitant medication with no or minimal CYP3A4/5 inhibition potential is recommended. Although INLYTA dose adjustment has not been studied in patients receiving strong CYP3A4/5 inhibitors, if a strong CYP3A4/5 inhibitor must be co-administered, a dose decrease of INLYTA by approximately half is recommended, as this dose reduction is predicted to adjust the axitinib area under the plasma concentration vs time curve (AUC) to the range observed without inhibitors. The subsequent doses can be increased or decreased based on individual safety and tolerability. If co-administration of the strong inhibitor is discontinued, the INLYTA dose should be returned (after 3 – 5 half-lives of the inhibitor) to that used prior to initiation of the strong CYP3A4/5 inhibitor.
    Hepatic Impairment: No starting dose adjustment is required when administering INLYTA to patients with mild hepatic impairment (Child-Pugh class A). Based on the pharmacokinetic data, the INLYTA starting dose should be reduced by approximately half in patients with baseline moderate hepatic impairment (Child-Pugh class B). The subsequent doses can be increased or decreased based on individual safety and tolerability. INLYTA has not been studied in patients with severe hepatic impairment (Child-Pugh class C).


    Indications

    Treatment of advanced renal cell carcinoma (RCC) after failure of one prior systemic therapy.


    Contra-Indications

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


    Special Precautions

    Hypertension and Hypertensive Crisis: Blood pressure should be well-controlled prior to initiating axitinib. Patients should be monitored for hypertension and treated as needed with standard anti-hypertensive therapy. In the case of persistent hypertension despite use of anti-hypertensive medications, reduce the axitinib dose. Discontinue axitinib if hypertension is severe and persistent despite anti-hypertensive therapy and dose reduction of INLYTA, and discontinuation should be considered if there is evidence of hypertensive crisis.
    Arterial Thromboembolic Events: Use axitinib with caution in patients who are at risk for, or who have a history of, these events. Axitinib has not been studied in patients who had an arterial thromboembolic event within the previous 12 months.
    Venous Thromboembolic Events: Use axitinib with caution in patients who are at risk for, or who have a history of, these events. Axitinib has not been studied in patients who had a venous thromboembolic event within the previous 6 months.
    Hemorrhage: The drug has not been studied in patients who have evidence of untreated brain metastasis or recent active gastrointestinal bleeding and should not be used in those patients. If any bleeding requires medical intervention, temporarily interrupt the axitinib dose.
    Cardiac Failure: In a controlled clinical study with INLYTA for the treatment of patients with RCC, cardiac failure was reported in 6/359 patients (2%) receiving INLYTA and 3/355 patients (1%) receiving sorafenib. Grade 3/4 cardiac failure was observed in 2/359 patients (1%) receiving INLYTA and 1/355 patients (<1%) receiving sorafenib. Fatal cardiac failure was reported in 2/359 patients (1%) receiving INLYTA and 1/355 patients (<1%) receiving sorafenib. Monitor for signs or symptoms of cardiac failure throughout treatment with INLYTA. Management of cardiac failure may require permanent discontinuation of INLYTA.
    Gastrointestinal Perforation and Fistula Formation: Monitor for symptoms of gastrointestinal perforation or fistula periodically throughout treatment with axitinib.
    Thyroid Dysfunction: Monitor thyroid function before initiation of, and periodically throughout, treatment with axitinib. Treat hypothyroidism and hyperthyroidism according to standard medical practice to maintain euthyroid state.
    Risk of Impaired Wound Healing: Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, INLYTA has the potential to adversely affect wound healing.
    Withhold INLYTA for at least 2 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of INLYTA after resolution of wound healing complications has not been established.
    Reversible Posterior Leukoencephalopathy Syndrome: RPLS is a neurological disorder which can present with headache, seizure, lethargy, confusion, blindness and other visual and neurologic disturbances. Mild to severe hypertension may be present. Magnetic resonance imaging is necessary to confirm the diagnosis of RPLS. Discontinue axitinib in patients developing RPLS. The safety of reinitiating this drug therapy in patients previously experiencing RPLS is not known.
    Proteinuria: Monitoring for proteinuria before initiation of, and periodically throughout, treatment with this drug is recommended. For patients who develop moderate to severe proteinuria, reduce the dose or temporarily interrupt axitinib treatment.
    Elevation of hepatic enzymes: Monitor ALT, aspartate aminotransferase (AST) and bilirubin before initiation of and periodically throughout treatment with axitinib.
    Renal Impairment: No dedicated renal impairment trial for axitinib has been conducted. Based on the population pharmacokinetic analyses, no significant difference in axitinib clearance was observed in patients with pre-existing mild to severe renal impairment (15 mL/min ≤creatinine clearance [CLcr] <89 mL/min). No starting dose adjustment is needed for patients with pre-existing mild to severe renal impairment. Caution should be used in patients with end-stage renal disease (CLcr <15 mL/min).
    Hepatic Impairment: No starting dose adjustment is required when administering this drug to patients with mild hepatic impairment. Based on the pharmacokinetic data, the axitinib starting dose should be reduced by approximately half in patients with baseline moderate hepatic impairment (Child-Pugh class B). The subsequent doses can be increased or decreased based on individual safety and tolerability. this drug has not been studied in patients with severe hepatic impairment (Child-Pugh class C).
    Embryo-Fetal Toxicity: Based on its mechanism of action and findings from animal studies, INLYTA can cause fetal harm when administered to a pregnant woman. There are no available human data to inform the drug-associated risk. In developmental toxicity studies in mice, axitinib was teratogenic, embryotoxic and fetotoxic at maternal exposures that were lower than human exposures at the recommended clinical dose. Advise females of reproductive potential of the potential risk to the fetus and to use effective contraception during treatment with INLYTA and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with INLYTA and for 1 week after the last dose.
    Lactose: This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
    See prescribing information for full details.


    Side Effects

    The most common (≥20%) adverse reactions observed following treatment with INLYTA were diarrhea, hypertension, fatigue, decreased appetite, nausea, dysphonia, palmar-plantar erythrodysesthesia (hand-foot) syndrome, weight decreased, vomiting, asthenia, and constipation.
    See prescribing information for full details.


    Drug interactions

    CYP3A4/5 Inhibitors: Co-administration of ketoconazole, a strong inhibitor of CYP3A4/5, increased the plasma exposure of axitinib in healthy volunteers. Co-administration of INLYTA with strong CYP3A4/5 inhibitors should be avoided. Grapefruit or grapefruit juice may also increase axitinib plasma concentrations and should be avoided. Selection of concomitant medication with no or minimal CYP3A4/5 inhibition potential is recommended. If a strong CYP3A4/5 inhibitor must be co-administered, the INLYTA dose should be reduced.
    CYP3A4/5 Inducers: Co-administration of rifampin, a strong inducer of CYP3A4/5, reduced the plasma exposure of axitinib in healthy volunteers. Co-administration of INLYTA with strong CYP3A4/5 inducers (e.g., rifampin, dexamethasone, phenytoin, carbamazepine, rifabutin, rifapentin, phenobarbital, and St. John’s wort) should be avoided. Selection of concomitant medication with no or minimal CYP3A4/5 induction potential is recommended. Moderate CYP3A4/5 inducers (e.g., bosentan, efavirenz, etravirine, modafinil, and nafcillin) may also reduce the plasma exposure of axitinib and should be avoided if possible.


    Pregnancy and Lactation

    Pregnancy: Based on findings in animal studies and its mechanism of action, INLYTA can cause fetal harm when administered to a pregnant woman. There are no available human data to inform the drug-associated risk. In developmental toxicity studies, axitinib was teratogenic, embryotoxic and fetotoxic in mice at exposures lower than human exposures at the recommended starting dose (see Data). Advise females of reproductive potential of the potential risk to a fetus.
    Lactation: There are no data on the presence of axitinib in human milk, or its effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in a breastfed child from INLYTA, advise lactating women not to breastfeed during treatment and for 2 weeks after the final dose.
    See prescribing information for full details.


    Overdose

    There is no specific treatment for INLYTA overdose.
    In a controlled clinical study with axitinib for the treatment of patients with RCC, 1 patient inadvertently received a dose of 20 mg twice daily for 4 days and experienced dizziness (Grade 1).
    In a clinical dose finding study with axitinib, subjects who received starting doses of 10 mg twice daily or 20 mg twice daily experienced adverse reactions which included hypertension, seizures associated with hypertension, and fatal hemoptysis.
    In cases of suspected overdose, the drug should be withheld and supportive care instituted.


    Important notes

    Storage: Store below 30°C.
    Shelf life after first opening the bottle: 6 months.


    Manufacturer
    Pfizer Germany
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