nintedanib (Rx)

Brand and Other Names:Ofev
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 100mg
  • 150mg
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Idiopathic Pulmonary Fibrosis

150 mg PO q12hr with food

Dosage Modifications

Gastrointestinal toxicity (Diarrhea, nausea, and/or vomiting) or other forms of toxicities

  • Temporarily interrupt treatment if symptoms persist despite hydration or antidiarrheal/antiemetic medication
  • If unable to resume at full dose, decrease dose to 100 mg PO BID, which subsequently may be increased to the full dosage
  • Discontinue if patient does not tolerate 100 mg BID

Elevated liver enzymes

  • AST/ALT >3 to <5x ULN without signs of severe liver damage: Interrupt treatment or reduce to 100 mg BID; once LFTs return to normal, may reintroduce at 100 mg BID, which subsequently may be increased to 150 mg BID
  • AST/ALT >5x ULN or >3x ULN with signs/symptoms of severe liver damage: Discontinue

Hepatic impairment

  • Mild (Child Pugh A): 100 mg BID; consider treatment interruption if patient does not tolerate 100 mg BID, or discontinue treatment to manage adverse reactions
  • Moderate-to-severe (Child Pugh B or C): Not recommended (not studied)

Renal impairment

  • Mild-to-moderate (≥30 mL/min): No dosage adjustment required
  • Severe (CrCl <30 mL/min) or ESRD: Not studied

Dosing Considerations

Conduct liver function tests and a pregnancy test prior to initiating drug (see Cautions and Pregnancy)

Systemic Sclerosis (Orphan)

Orphan designation for treatment of systemic sclerosis (including the associated interstitial lung disease)

Sponsor

  • Boehringer Ingelheim Pharmaceuticals, Inc; 900 Ridgebury Rd, Box 368; Ridgefield, CT 06877

Mesothelioma (Orphan)

Orphan designation for treatment of mesothelioma

Sponsor

  • Boehringer Ingelheim Pharmaceuticals, Inc; 900 Ridgebury Rd, Box 368; Ridgefield, CT 06877

Safety and efficacy not established

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Interactions

Interaction Checker

and nintedanib

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            Diarrhea (62%)

            Nausea (24%)

            Abdominal pain (15%)

            Elevated liver enzymes (14%)

            Vomiting (12%)

            Decreased appetite (11%)

            1-10%

            Decreased weight (10%)

            Bleeding events (10%)

            Headache (8%)

            Hypertension (5%)

            Arterial thromboembolic events (2.5%)

            Myocardial infarction (1.5%)

            Hypothyroidism (1.1%)

            <1%

            Gastrointestinal perforation (0.3%)

            Postmarketing Reports

            Pancreatitis

            Thrombocytopenia

            Drug-induced liver injury

            Rash

            Pruritus

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            Warnings

            Contraindications

            None

            Cautions

            Severe liver injury with fatal outcome reported; majority of hepatic events occur within first 3 months of treatment; conduct liver function tests (ALT, AST, and bilirubin) before initiating, monthly for 3 months, and then q3months thereafter and as clinically indicated (see Dosage Modifications)

            Diarrhea, nausea, and/or vomiting may occur; treat with adequate hydration and antidiarrheal/antiemetic medications; if persists, treatment interruption and dose reduction may be needed (see Adult Dosing, Dosage Modifications)

            Arterial thromboembolic events reported, including myocardial infarction; caution when treatment patients at higher cardiovascular risk

            May increase risk of bleeding or gastrointestinal perforation (based on mechanism of action [VEGFR inhibition]); monitor for bleeding if on full anticoagulant therapy and adjust anticoagulation treatment as needed

            Smoking associated with decreased systemic exposure; encourage patients to quit smoking

            Can cause fetal harm; use adequate contraception during treatment and for at least 3 months after the last dose

            In postmarketing period non-serious and serious bleeding events reported; use therapy in patients with known risk of bleeding only if anticipated benefit outweighs potential risk

            In postmarketing period, cases of gastrointestinal perforations reported; use caution when treating patients who have had recent abdominal surgery, previous history of diverticular disease or receiving concomitant corticosteroids or NSAIDs; discontinue therapy in patients who develop gastrointestinal perforation; only use in patients with known risk of gastrointestinal perforation if anticipated benefit outweighs potential risk

            Drug interaction overview

            • Nintedanib is a substrate of CYP3A4 and P-gp transporter
            • Coadministration with potent P-gp or CYP3A4 inhibitors may increase systemic exposure of nintedanib (monitor closely)
            • Coadministration with P-gp or CYP3A4 inducers may decrease systemic exposure to nintedanib by 50%; avoid coadministration
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            Pregnancy & Lactation

            Pregnancy

            Based on findings from animal studies and its mechanism of action, can cause fetal harm when administered to pregnant women

            In animal studies of pregnant rats and rabbits treated during organogenesis, nintedanib caused embryo-fetal deaths and structural abnormalities at less than (rats) and approximately 5 times (rabbits) the maximum recommended human dose

            Verify the pregnancy status of females of reproductive potential prior to treatment

            Contraception

            • Advise females of reproductive potential to avoid becoming pregnant while receiving nintedanib
            • Use effective contraception during treatment, and for at least 3 months after taking the last dose

            Infertility

            • Based on animal data, may reduce fertility in females of reproductive potential

            Lactation

            There is no information on the presence of nintedanib in human milk, the effects on the breast-fed infant or the effects on milk production

            Nintedanib and/or its metabolites are present in the milk of lactating rats

            Because of the potential for serious adverse effects in breastfed infants, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Tyrosine kinase inhibitor; targets growth factors, which have been shown to be potentially involved in pulmonary fibrosis (eg, vascular endothelial growth factor receptor [VEGFR], fibroblast growth factor receptor [FGFR], platelet-derived growth factor receptor [PDGF])

            Binds competitively to the adenosine triphosphate (ATP)-binding pocket of these receptors and blocks the intracellular signaling, which is crucial for the proliferation, migration, and transformation of fibroblasts, representing essential mechanisms of the IPF pathology

            Absorption

            Bioavailability: 4.7%; undergoes substantial first-pass metabolism

            Peak plasma concentration: 2-4 hr

            Food increases systemic exposure by ~20% and delays peak level to ~4 hr

            Distribution

            Protein bound: 97.8%

            Vd: 1050 L

            Metabolism

            Hydrolytic cleavage by esterases resulting in the free acid moiety BIBF 1202 is the prevalent metabolic pathway (~25%); BIBF 1202 is subsequently glucuronidated by UGT enzymes, namely UGT 1A1, UGT 1A7, UGT 1A8, and UGT 1A10 to BIBF 1202 glucuronide

            Only a minor extent of the biotransformation consists of CYP pathways (~5%), with CYP3A4 being the predominant enzyme involved

            Elimination

            Excretion: 93.4% feces/biliary; 0.65% urine

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            Administration

            Oral Administration

            Take with food

            Swallow capsule whole with liquid; do not chew or crush (bitter taste); effect of crushing on the pharmacokinetics is unknown

            If a dose is missed, the next dose should be taken at the next scheduled time; advise the patient to not make up for a missed dose

            Not to exceed 300 mg/day

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            Images

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.