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    Active Ingredient
    Sotorasib 120 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Film Coated Tablets

    120 mg

    120 tabs x 120mg , 240 tabs x 120mg

    not in the basket chart

    Dosage

    The recommended dose is 960 mg sotorasib (eight 120 mg tablets) once daily, at the same time each day.
    Duration of treatment:
    Treatment with sotorasib is recommended until disease progression or unacceptable toxicity.
    Missed doses or vomiting:
    If less than 6 hours have passed since the scheduled time of dosing, the patient should take the dose as normal. If more than 6 hours have passed since the scheduled time of dosing, the patient must not take the dose. Treatment should be continued as prescribed the next day.
    If vomiting occurs after taking the drug, the patient must not take an additional dose on the same day, and treatment must be continued as prescribed the next day.
    Dose modifications:
    Dosing should be modified based on the drug toxicity. If toxicity events occur, a maximum of two dose reductions are permitted. This medicinal product must be discontinued if patients are unable to tolerate the minimum dose of 240 mg once daily. See prescribing information for more information about dose reduction rules.
    Elderly:
    The limited data on the safety and efficacy in patients aged 75 years and older do not suggest that a dose adjustment is required in elderly patients.
    Hepatic impairment:
    No dose adjustment is recommended for patients with mild hepatic impairment (AST or ALT < 2.5 × ULN or total bilirubin < 1.5 × ULN). Administration of sotorasib in subjects with moderate and severe hepatic impairment is not recommended.
    Renal impairment:
    No dose adjustment is recommended for patients with mild renal impairment (creatine clearance, CrCL, ≥ 60 mL/min). The drug has not been studied in patients with moderate or severe renal impairment (CrCL < 60 mL/min). Therefore, caution should be exercised when treating patients with moderate, severe and end stage renal impairment.
    Paediatric population:
    The safety and efficacy in children and adolescents under the age of 18 years have not yet been established.
    Method of administration:
    For oral use. The tablets must be swallowed whole. There are no data to support the administration if the tablets are chewed, crushed, or split but the tablets can be dispersed in water. The tablets can be taken with or without food.
    Administration to patients who have difficulty swallowing solids:
    Patients should disperse tablets in 120 mL of non-carbonated, room-temperature water, without crushing them. Other liquids must not be used. Patients should stir until tablets are dispersed into small pieces (the tablet will not dissolve completely) and drink immediately. The appearance of the mixture may range from pale to bright yellow. The container must be rinsed with an additional 120 mL of water, which should be drunk immediately. If it is not drunk immediately, patients must stir again to ensure that the tablets are dispersed. The dispersion must be discarded if it is not drunk within 2 hours.


    Indications

    Treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an approved test, who have received at least one prior systemic therapy.


    Contra-Indications

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


    Special Precautions

    Hepatotoxicity:
    Sotorasib can cause hepatotoxicity, which may lead to drug-induced liver injury (DILI) and hepatitis. Sotorasib has been associated with transient elevations of serum transaminases (ALT and AST). These elevations improved or resolved with dose modification or permanent discontinuation of treatment and did not result in any cases of liver failure or fatal cases in clinical studies. Among patients who experienced hepatotoxicity, 38% had hepatotoxicity leading to dose interruption or dose reduction. Overall, 26% of patients with hepatotoxicity received concurrent corticosteroids. Cases of liver enzyme increase can be asymptomatic. Patients should be monitored for liver function (ALT, AST, and total bilirubin) prior to the start of the medication, every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations. Based on the severity of the laboratory abnormalities, treatment must be stopped until recovered to ≤ grade 1 or to baseline grade, and the dose must either be modified or permanently discontinue treatment as recommended .
    Interstitial Lung Disease (ILD)/pneumonitis:
    ILD/pneumonitis occurred in patients treated with the drug with prior exposure to immunotherapy or radiotherapy. Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g. dyspnoea, cough, fever). Immediately withhold treatment in patients with suspected ILD/pneumonitis and permanently discontinue the medication if no other potential causes of ILD/pneumonitis are identified.
    Lactose intolerance:
    This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.
    Sodium:
    This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.


    Side Effects

    Very common: Anaemia, headache, cough, dyspnoea, diarrhoea, nausea, vomiting, constipation, abdominal paina, arthralgia, back pain, fatigue, pyrexia, aspartate aminotransferase increased, alanine aminotransferase increased.
    Common: Drug-induced liver injury, blood alkaline phosphatase increased, blood bilirubin increased , gamma-glutamyltransferase increased.
    See prescribing information for full details.


    Drug interactions

    Effects of other medicinal products on sotorasib:
    Acid-reducing agents: Co-administration of sotorasib with a PPI (omeprazole) or an H2 receptor antagonist (famotidine) led to a decrease in sotorasib concentrations. Under fed conditions (standard-calorie moderate-fat meals), co-administration of multiple doses of omeprazole with a single dose of 960 mg sotorasib decreased sotorasib Cmax by 65% and AUC by 57%. Co-administration of a single dose of famotidine given 10 hours prior and 2 hours after a single dose of 960 mg sotorasib decreased sotorasib Cmax by 35% and AUC by 38%. Under fasted conditions, co-administration of multiple doses of omeprazole with a single dose of 960 mg sotorasib decreased sotorasib Cmax by 57% and AUC by 42%. Co-administration of PPIs and H2 receptor antagonists with sotorasib is not recommended because the impact on sotorasib efficacy is unknown. If treatment with an acid-reducing agent is required, sotorasib should be taken 4 hours before or 10 hours after administration of a local antacid.
    Co-administration of multiple-dose itraconazole (a strong CYP3A4 and P-gp inhibitor) did not increase sotorasib exposures to a clinically significant extent. No dose adjustment is recommended when co-administered with CYP3A4 inhibitors.
    Strong CYP3A4 inducers : Co-administration of sotorasib with multiple doses of a strong CYP3A4 inducer (rifampicin) decreased sotorasib Cmax by 35% and AUC by 51%. Co-administration of strong CYP3A4 inducers (e.g. rifampicin, carbamazepine, enzalutamide, mitotane, phenytoin and St. John’s wort) with sotorasib is not recommended because they may decrease sotorasib exposure.
    Effect of sotorasib on other medicinal products:
    CYP3A4 substrates: Sotorasib is a moderate CYP3A4 inducer. Co-administration of sotorasib with CYP3A4 substrates led to a decrease in their plasma concentrations, which may reduce the efficacy of these substrates. Co-administration of sotorasib with midazolam (a sensitive CYP3A4 substrate) decreased midazolam Cmax by 48% and AUC by 53%.
    Avoid co-administration with CYP3A4 substrates with narrow therapeutic indices, including but not limited to alfentanil, ciclosporin, dihydroergotamine, ergotamine, fentanyl, hormonal contraceptives, pimozide, quinidine, sirolimus and tacrolimus. If co-administration cannot be avoided, adjust the CYP3A4 substrate dose in accordance with the current summary of product characteristics.
    CYP2B6, CYP2C8, CYP2C9 and CYP2C19 substrates: In vitro data indicated that sotorasib may have the potential to induce CYP2B6, CYP2C8, CYP2C9 and CYP2C19; the clinical relevance of these findings is unknown. When sotorasib is co-administered with medicinal products metabolised by these enzymes, appropriate monitoring is recommended.
    CYP2D6 substrates:  In vitro data indicated that sotorasib may have the potential to inhibit CYP2D6, the clinical relevance of these findings is unknown. When sotorasib is co-administered with CYP2D6 substrates (e.g. flecainide, propafenone, metoprolol), appropriate monitoring is recommended.
    BCRP substrates: Sotorasib is a weak BCRP inhibitor. Co-administration with a BCRP substrate led to an increase in the plasma concentrations of the BCRP substrate, which may increase the effect of the substrate.
    Co-administration with rosuvastatin (a BCRP substrate) increased the rosuvastatin Cmax by 70% and AUC by 34%.
    When Sotorasib is co-administered with a BCRP substrates, including but not limited to lapatinib, methotrexate, mitoxantrone, rosuvastatin and topotecan, monitor for adverse reactions of the BCRP substrate and reduce the BCRP substrate dose in accordance with its current summary of product characteristics.
    Effect of sotorasib on P-gp substrates: Co-administration of sotorasib with digoxin (a P-glycoprotein [P-gp] substrate) increased digoxin Cmax by 1.9-fold and AUCinf by 1.2-fold of digoxin administered alone. Co-administration with P-gp substrates with narrow therapeutic indices is not recommended. If co-administration cannot be avoided, adjust the P-gp substrate dosage in accordance with the current summary of product characteristics.


    Pregnancy and Lactation

    Women of childbearing potential/Contraception:
    Women of childbearing potential must be advised to avoid pregnancy while on sotorasib. Female patients of child-bearing potential receiving sotorasib must use highly effective contraceptive methods during treatment and for at least 7 days following the last dose of sotorasib. Sotorasib may reduce the effectiveness of hormonal contraceptives, and therefore women using hormonal contraceptives should add a barrier method.
    Pregnancy:
    There are no data from the use of sotorasib in pregnant women. Studies in animals have shown reproductive toxicity. Sotorasib is not recommended during pregnancy and in women of childbearing potential not using contraception. Patients must be informed of the potential hazards to the foetus if sotorasib is used during pregnancy, or if the patient becomes pregnant while taking sotorasib.
    Breast-feeding:
    It is unknown if sotorasib or its metabolites are excreted in human milk. A risk to breast-fed newborns/infants cannot be excluded. This medicinal product should not be used during breast-feeding.
    Fertility:
    There are no clinical studies to evaluate the effect of sotorasib on fertility.


    Overdose

    In the event of an overdose, the patient should be treated symptomatically, and supportive measures instituted as required. There is no specific antidote for overdose with sotorasib.


    Important notes

    The presence of a KRAS G12C mutation must be confirmed using a validated test prior to initiation of sotorasib therapy.


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