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  • Ofev
    / Boehringer Ingelheim


    Active Ingredient
    Nintedanib (As Esliate) 100 mg, 150 mg

    Status in Israel
    RX

    Presentation and Status in Health Basket

    Presentation Basket Yarpa Pharmasoft

    Soft Capsules

    60 X 100 mg

    partial basket chart 30846 15460

    Soft Capsules

    60 X 150 mg

    partial basket chart 30881 15461

    Related information


    Dosage

    Testing Prior to OFEV Administration: Conduct liver function tests and a pregnancy test prior to initiating treatment with Nintedanib.
    Recommended Dosage: The recommended dosage of Nintedanib is 150 mg twice daily administered approximately 12 hours apart.
    OFEV capsules should be taken with food and swallowed whole with liquid. OFEV capsules should not be chewed or crushed because of a bitter taste. The effect of chewing or crushing of the capsule on the pharmacokinetics of nintedanib is not known.
    If a dose of OFEV is missed, the next dose should be taken at the next scheduled time. Advise the patient to not make up for a missed dose. Do not exceed the recommended maximum daily dosage of 300 mg.
    In patients with mild hepatic impairment (Child Pugh A), the recommended dosage of OFEV is 100 mg twice daily approximately 12 hours apart taken with food.
    Dosage Modification due to Adverse Reactions: In addition to symptomatic treatment, if applicable, the management of adverse reactions of OFEV may require dose reduction or temporary interruption until the specific adverse reaction resolves to levels that allow continuation of therapy. OFEV treatment may be resumed at the full dosage (150 mg twice daily), or at the reduced dosage (100 mg twice daily), which subsequently may be increased to the full dosage. If a patient does not tolerate 100 mg twice daily, discontinue treatment with OFEV.
    Dose modifications or interruptions may be necessary for liver enzyme elevations. Conduct liver function tests (aspartate aminotransferase (AST), alanine aminotransferase (ALT), and bilirubin) prior to initiation of treatment with OFEV, at regular intervals during the first three months of treatment, and periodically thereafter or as clinically indicated. Measure liver tests promptly in patients who report symptoms that may indicate liver injury, including fatigue, anorexia, right upper abdominal discomfort, dark urine or jaundice.
    Discontinue OFEV in patients with AST or ALT greater than 3 times the upper limit of normal (ULN) with signs or symptoms of liver injury and for AST or ALT elevations greater than 5 times the upper limit of normal. For AST or ALT greater than 3 times to less than 5 times the ULN without signs of liver damage, interrupt treatment or reduce OFEV to 100 mg twice daily. Once liver enzymes have returned to baseline values, treatment with OFEV may be reintroduced at a reduced dosage (100 mg twice daily), which subsequently may be increased to the full dosage (150 mg twice daily).
    In patients with mild hepatic impairment (Child Pugh A), consider treatment interruption, or discontinuation for management of adverse reactions.


    Indications

    Indicated for the treatment of idiopathic pulmonary fibrosis (IPF) in adults.


    Contra-Indications

    Hypersensitivity to the active substance or any of the excipients.


    Special Precautions

    Hepatic Impairment: Treatment with Nintedanib is not recommended in patients with moderate (Child Pugh B) or severe (Child Pugh C) hepatic impairment. Patients with mild hepatic impairment (Child Pugh A) can be treated with a reduced dose of Nintedanib.
    Elevated Liver Enzymes and Drug-Induced Liver Injury: Cases of drug-induced liver injury (DILI) have been observed with OFEV treatment. In the post-marketing period, non-serious and serious cases of DILI, including severe liver injury with fatal outcome, have been reported. The majority of hepatic events occur within the first three months of treatment. In clinical trials, administration of OFEV was associated with elevations of liver enzymes (ALT, AST, ALKP, GGT) and bilirubin. Liver enzyme and bilirubin increases were reversible with dose modification or interruption in the majority of cases. The majority (94%) of patients with ALT and/or AST elevations had elevations less than 5 times ULN.. The majority (95%) of patients with bilirubin elevations had elevations less than 2 times ULN. Patients with a low body weight (less than 65 kg), Asian, and female patients may have a higher risk of elevations in liver enzymes. Nintedanib exposure increased with patient age, which may also result in a higher risk of increased liver enzymes.
    Gastrointestinal Disorders
    Diarrhea: Diarrhea was the most frequent gastrointestinal event reported in 62% versus 18% of patients treated with Nintedanib and placebo, respectively. In most patients, the event was of mild to moderate intensity and occurred within the first 3 months of treatment.
    Nausea and Vomiting: Nausea was reported in 24% versus 7% and vomiting was reported in 12% versus 3% of patients treated with Nintedanib and placebo, respectively. In most patients, these events were of mild to moderate intensity. For nausea or vomiting that persists despite appropriate supportive care including anti-emetic therapy, dose reduction or treatment interruption may be required. Nintedanib treatment may be resumed at the full dosage (150 mg twice daily), or at the reduced dosage (100 mg twice daily), which subsequently may be increased to the full dosage. If severe nausea or vomiting does not resolve, discontinue treatment with Nintedanib.
    Embryo-Fetal Toxicity: Nintedanib can cause fetal harm when administered to a pregnant woman. If Nintedanib is used during pregnancy, or if the patient becomes pregnant while taking Nintedanib, the patient should be advised of the potential hazard to a fetus. Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with Nintedanib and to use adequate contraception during treatment and at least 3 months after the last dose of Nintedanib.
    Arterial Thromboembolic Events: Arterial thromboembolic events have been reported in patients taking Nintedanib. Use caution when treating patients at higher cardiovascular risk including known coronary artery disease. Consider treatment interruption in patients who develop signs or symptoms of acute myocardial ischemia.
    Risk of Bleeding: Based on the mechanism of action (VEGFR inhibition), Nintedanib may increase the risk of bleeding.
    Gastrointestinal Perforation: Based on the mechanism of action, Nintedanib may increase the risk of gastrointestinal perforation.
    See prescribing information for full details. 


    Side Effects

    Elevated Liver Enzymes and Drug-Induced Liver Injury, Gastrointestinal Disorders, Embryo-Fetal Toxicity, Arterial Thromboembolic Events, Risk of Bleeding, Gastrointestinal Perforation, Pancreatitis, Trombocytopenia.
    See prescribing information for full details.


    Drug interactions

    P-glycoprotein (P-gp) and CYP3A4 Inhibitors and Inducers: Nintedanib is a substrate of P-gp and, to a minor extent, CYP3A4 . Coadministration with oral doses of a P-gp and CYP3A4 inhibitor, ketoconazole, increased exposure to nintedanib by 60%. Concomitant use of P-gp and CYP3A4 inhibitors (e.g., erythromycin) with Nintedanib may increase exposure to nintedanib. In such cases, patients should be monitored closely for tolerability of Nintedanib. Management of adverse reactions may require interruption, dose reduction, or discontinuation of therapy with NintedanibCoadministration with oral doses of a P-gp and CYP3A4 inducer, rifampicin, decreased exposure to nintedanib by 50%. Concomitant use of P-gp and CYP3A4 inducers (e.g., carbamazepine, phenytoin, and St. John’s wort) with Nintedanib should be avoided as these drugs may decrease exposure to nintedanib.
    Anticoagulants: Nintedanib is a VEGFR inhibitor, and may increase the risk of bleeding. Monitor patients on full anticoagulation therapy closely for bleeding and adjust anticoagulation treatment as necessary.
    See prescribing information for full details.


    Pregnancy and Lactation

    Pregnancy: Women of childbearing potential should be advised to avoid becoming pregnant while receiving treatment with Nintedanib and to use adequate contraception during treatment and at least 3 months after the last dose of Nintedanib.
    LactationBecause of the potential for serious adverse reactions in nursing infants from Nintedanib, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.
    See prescribing information for full details.


    Overdose

    In the trials, one patient was inadvertently exposed to a dose of 600 mg daily for a total of 21 days. A non-serious adverse event (nasopharyngitis) occurred and resolved during the period of incorrect dosing, with no onset of other reported events. Overdose was also reported in two patients in oncology studies who were exposed to a maximum of 600 mg twice daily for up to 8 days. Adverse events reported were consistent with the existing safety profile of Nintedanib. Both patients recovered. In case of overdose, interrupt treatment and initiate general supportive measures as appropriate.


    Important notes

    Storage: Do not store above 25°C. Store in the original package in order to protect from moisture.
    Before/after meal: should be taken with food.
    Lactose: No content of lactose.


    Manufacturer
    Boehringer Ingelheim GmbH
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