nintedanib (Rx)

Brand and Other Names:Ofev
  • Print

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

capsule

  • 100mg
  • 150mg

Idiopathic Pulmonary Fibrosis

Indicated for idiopathic pulmonary fibrosis

150 mg PO q12hr

Systemic Sclerosis-associated Interstitial Lung Disease

Indicated to slow the rate of decline in pulmonary function in patients with systemic sclerosis-associated interstitial lung disease (SSc-ILD)

150 mg PO q12hr

Dosage Modifications

Dosage modifications due to adverse reactions

  • Adverse reactions may require dose reduction or temporary interruption until the specific adverse reaction resolves
  • Resumed at 150 mg q12hr, or at 100 mg q12hr, which subsequently may be increased to the full dose (150 mg q12hr)
  • If 100 mg q12hr is not tolerated, discontinue treatment

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 PO q12hr
  • Moderate-to-severe (Child Pugh B or C): Not recommended (not studied)

Renal impairment

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

Dosing Considerations

Laboratory testing before administration

  • Conduct liver function tests in all patients
  • Obtain pregnancy test in females of reproductive potential

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

Next:

Interactions

Interaction Checker

and nintedanib

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
             activity indicator 
            Previous
            Next:

            Adverse Effects

            >10%

            Idiopathic pulmonary fibrosis

            • Diarrhea (62%)
            • Nausea (24%)
            • Abdominal pain (15%)
            • Elevated liver enzymes (14%)
            • Vomiting (12%)
            • Decreased appetite (11%)

            SSc-ILD

            • Diarrhea (76%)
            • Nausea (32%)
            • Vomiting (25%)
            • Skin ulcer (18%)
            • Abdominal pain (18%)
            • Liver enzyme elevation (13%)
            • Decreased weight (12%)
            • Fatigue (11%)

            1-10%

            Idiopathic pulmonary fibrosis

            • Decreased weight (10%)
            • Bleeding events (10%)
            • Headache (8%)
            • Hypertension (5%)
            • Arterial thromboembolic events (2.5%)
            • Myocardial infarction (1.5%)
            • Bronchitis (1.5%)
            • Hypothyroidism (1.1%)

            SSc-ILD

            • Decreased appetite (9%)
            • Headache (9%)
            • Pyrexia (6%)
            • Back pain (6%)
            • Dizziness (6%)
            • Hypertension (5%)

            <1%

            Idiopathic pulmonary fibrosis

            • Pneumonia (0.7%)
            • Lung neoplasm malignant (0.3%)
            • Gastrointestinal perforation (0.3%)

            Postmarketing Reports

            Pancreatitis

            Thrombocytopenia

            Drug-induced liver injury

            Rash

            Pruritus

            Previous
            Next:

            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

            Not recommended in patients with moderate or severe hepatic impairment (Child Pugh B or C); reduced dose for patients with mild hepatic impairment (Child Pugh A)

            Nausea, and/or vomiting may occur; treat with adequate hydration and antidiarrheal/antiemetic medications; if persists, treatment interruption and dose reduction may be needed

            Diarrhea may occur; treat at first signs with adequate hydration and antidiarrheal medication (eg, loperamide); consider treatment interruption if diarrhea continues; treatment may be resumed at full dosage (150 mg twice daily), or at reduced dosage (100 mg twice daily); may subsequently increase to full dosage; if severe diarrhea persists despite symptomatic treatment, discontinue treatment

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

            May increased 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 the anticipated benefit outweighs the 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
            Previous
            Next:

            Pregnancy & Lactation

            Pregnancy

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

            Verify pregnancy status of females of reproductive potential prior to treatment

            Animal data

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

            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.

            Previous
            Next:

            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

            Previous
            Next:

            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 dose missed, take next dose at next scheduled time; advise patient to not make up for a missed dose

            Storage

            Store at 25ºC (77ºF); excursions permitted to 15-30ºC (59-86ºF)

            Protect from exposure to high humidity and avoid excessive heat

            If repackaged, use USP tight container

            Keep out of reach of children

            Previous
            Next:

            Images

            Previous
            Next:

            Formulary

            FormularyPatient Discounts

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

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            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.
            Additional Offers
            Email to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Email Forms to Patient

            From:

            To:

            The recipient will receive more details and instructions to access this offer.

            By clicking send, you acknowledge that you have permission to email the recipient with this information.

            Previous
            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.