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  • LORVIQUA
    / Pfizer


    Active Ingredient
    Lorlatinib 25 mg, 100 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Film Coated Tablets

    90, 120 X 25 mg

    partial basket chart

    Film Coated Tablets

    30 X 100 mg

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    Related information


    Dosage

    The recommended dosage of lorlatinib is 100 mg orally once daily, with or without food, until disease progression or unacceptable toxicity.
    Swallow tablets whole. No information about chewing, crushing or splitting the tablets.
    Take lorlatinib at the same time each day. If a dose is missed, then take the missed dose unless the next dose is due within 4 hours. Do not take 2 doses at the same time to make up for a missed dose.
    Do not take an additional dose if vomiting occurs after lorlatinib but continue with the next scheduled dose.
    Dosage Modifications for Adverse Reactions:
    The recommended dose reductions are:
    – First dose reduction: lorlatinib 75 mg orally once daily
    – Second dose reduction: lorlatinib 50 mg orally once daily
    Permanently discontinue lorlatinib in patients who are unable to tolerate 50 mg orally once daily.
    Dosage modifications for adverse reactions:
    (Grade -based on National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0).
    Central Nervous System Effects
    Grade 1: Continue at the same dose or withhold the dose until recovery to baseline. Resume lorlatinib at the same dose or at a reduced dose.
    Grade 2 OR Grade 3:  Withhold dose until Grade 0 or 1. Resume lorlatinib at a reduced dose.
    Grade 4: Permanently discontinue lorlatinib.
    Hyperlipidemia
    Withhold lorlatinib until recovery of hypercholesterolemia and/or hypertriglyceridemia to less than or equal to Grade 2. Resume lorlatinib at the same dose.
    Grade 4 hypercholesterolemia OR Grade 4 hypertriglyceridemia: Withhold  lorlatinib until recovery of hypercholesterolemia and/or hypertriglyceridemia to less than or equal to Grade 2. Resume lorlatinib at the same dose.
    If severe hypercholesterolemia and/or hypertriglyceridemia recurs, resume lorlatinib at a reduced dose.
    Atrioventricular (AV) Block
    Second-degree AV block: Withhold lorlatinib until PR interval is less than 200 ms. Resume lorlatinib at a reduced dose.
    First occurrence of complete AV block: Withhold lorlatinib until pacemaker placed OR PR interval less than 200 ms.
    If a pacemaker is placed, resume lorlatinib at the same dose.
    If no pacemaker is placed, resume lorlatinib at a reduced dose.
    Recurrent complete AV block: Place pacemaker or permanently discontinue  lorlatinib.
    Interstitial Lung Disease (ILD)/Pneumonitis
    Permanently discontinue lorlatinib.
    Other Adverse Reactions
    Grade 1 OR Grade 2:
    Continue lorlatinib at same dose or reduced dose.
    Grade 3 OR Grade 4: Withhold lorlatinib until symptoms resolve to less than or equal to Grade 2 or baseline. Resume lorlatinib at reduced dose.
    See prescribing information for full details.


    Indications

    Treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) whose disease has progressed on
    – crizotinib and at least one other ALK inhibitor for metastatic disease;
    – alectinib as the first ALK inhibitor therapy for metastatic disease;
    – ceritinib as the first ALK inhibitor therapy for metastatic disease.


    Contra-Indications

    Patients taking strong CYP3A inducers, due to the potential for serious hepatotoxicity.
    Hypersensitivity to the active substance or to any of the excipients.


    Special Precautions

    Risk of Serious Hepatotoxicity with Concomitant Use of Strong CYP3A Inducers: Severe hepatotoxicity occurred in 10 of 12 healthy subjects receiving a single dose of lorlatinib with multiple daily doses of rifampin, a strong CYP3A inducer.
    Central Nervous System Effects: A broad spectrum of central nervous system (CNS) effects can occur in patients receiving lorlatinib. These include seizures, hallucinations, and changes in cognitive function, mood (including suicidal ideation), speech, mental status, and sleep.
    Hyperlipidemia: Increases in serum cholesterol and triglycerides can occur in patients receiving lorlatinib.
    Atrioventricular Block: PR interval prolongation and atrioventricular (AV) block can occur in patients receiving lorlatinib.
    Interstitial Lung Disease/Pneumonitis: Severe or life-threatening pulmonary adverse reactions consistent with interstitial lung disease (ILD)/pneumonitis can occur with lorlatinib.
    Embryo-Fetal Toxicity: Based on findings from animal studies and its mechanism of action, lorlatinib can cause fetal harm when administered to a pregnant woman.
    See prescribing information for full details.
    Lactose intolerance: This medicinal product contains lactose as an excipient. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption should not take this medicinal product.
    Dietary sodium: This medicinal product contains less than 1 mmol sodium (23 mg) per 25 mg or 100 mg tablet. Patients on low sodium diets should be informed that this product is essentially “sodium-free”.
    See prescribing information for full details.


    Side Effects

    Most common: Edema, peripheral neuropathy, cognitive effects, dyspnea, fatigue, weight gain, arthralgia, mood effects, and diarrhea, hypercholesterolemia, hypertriglyceridemia, anemia, hyperglycemia, increased AST, hypoalbuminemia, increased ALT, increased lipase, and increased alkaline phosphatase.
    See prescribing information for full details.


    Drug interactions

    Concomitant use of Strong or Moderate CYP3A Inducers: Lorlatinib  is contraindicated in patients taking strong CYP3A inducers. Discontinue strong CYP3A inducers for 3 plasma half-lives of the strong CYP3A inducer prior to initiating lorlatinib. Avoid concomitant use of lorlatinib with moderate CYP3A inducers.
    Dosage Modification for Strong CYP3A Inhibitors: Avoid concomitant use of lorlatinib with strong CYP3A inhibitors. If concomitant use with a strong CYP3A inhibitor cannot be avoided, reduce the starting dose of lorlatinib from 100 mg orally once daily to 75 mg orally once daily.
    In patients who have had a dose reduction to 75 mg orally once daily due to adverse reactions and who initiate a strong CYP3A inhibitor, reduce the lorlatinib dose to 50 mg orally once daily.
    If concomitant use of a strong CYP3A inhibitor is discontinued, increase the lorlatinib dose (after 3 plasma half-lives of the strong CYP3A inhibitor) to the dose that was used before starting the strong inhibitor.
    See prescribing information for full details.
    Effect of CYP3A Inducers: Concomitant use of lorlatinib with a strong CYP3A inducer decreased lorlatinib plasma concentrations, which may decrease the efficacy of lorlatinib. The effect of concomitant use of lorlatinib with a moderate CYP3A inducer on lorlatinib plasma concentrations has not been studied.
    Lorlatinib is contraindicated in patients taking strong CYP3A inducers. Discontinue strong CYP3A inducers for 3 plasma half-lives of the strong CYP3A inducer prior to initiating lorlatinib.
    Avoid concomitant use of lorlatinib with moderate CYP3A inducers. If concomitant use of moderate CYP3A inducers cannot be avoided, monitor ALT, AST, and bilirubin as recommended.
    Effect of Strong CYP3A Inhibitors: Concomitant use with a strong CYP3A inhibitor increased lorlatinib plasma concentrations, which may increase the incidence and severity of adverse reactions of lorlatinib.
    Avoid the concomitant use of lorlatinib with a strong CYP3A inhibitor. If concomitant use cannot be avoided, reduce lorlatinib dose as recommended.
    CYP3A Substrates: Concomitant use of lorlatinib decreases the concentration of CYP3A substrates, which may reduce the efficacy of these substrates. Avoid concomitant use of lorlatinib with CYP3A substrates, where minimal concentration changes may lead to serious therapeutic failures. If concomitant use is unavoidable, increase the CYP3A substrate dosage in accordance with approved product labeling.


    Pregnancy and Lactation

    Pregnancy: There are no available data on lorlatinib use in pregnant women.
    Females : Advise female patients of reproductive potential to use effective non-hormonal contraception during treatment with lorlatinib and for at least 6 months after the final dose. Advise females of reproductive potential to use a non-hormonal method of contraception, because lorlatinib can render hormonal contraceptives ineffective.
    Males: Based on genotoxicity findings, advise males with female partners of reproductive potential to use effective contraception during treatment with lorlatinib and for at least 3 months after the final dose.
    LactationThere are no data on the presence of lorlatinib or its metabolites in either human or animal milk or its effects on the breastfed infant or on milk production. Because of the potential for serious adverse reactions in breastfed infants, instruct women not to breastfeed during treatment with lorlatinib and for 7 days after the final dose.
    See prescribing information for full details.  


    Important notes

    Storage: This medicinal product does not require any special storage conditions.


    Manufacturer
    Pfizer Manufacturing Deutschland GmbH, Germany
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