tepotinib (Rx)

Brand and Other Names:Tepmetko
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 225mg

Non–Small Cell Lung Cancer

Indicated for metastatic non–small cell lung cancer (NSCLC) in adults harboring mesenchymal-epithelial transition (MET) exon 14 (ex14) skipping alterations

450 mg PO qDay

Continue until disease progression or unacceptable toxicity

Dosage Modifications

Recommended dose reduction to manage adverse reactions: 225 mg PO qDay

Permanently discontinue if unable to tolerate 225 mg PO qDay

Interstitial lung disease (ILD)/ pneumonitis

  • Suspected ILD (any grade): Withhold
  • Confirmed ILD: Permanently discontinue

Increased AST/ALT and/or total bilirubin

  • Grade 3 increased AST/ALT without increased total bilirubin
    • Withhold until recovery to baseline ALT/AST
    • If recovered to baseline ≤7 days, resume at same dose; otherwise, resume at a reduced dose
  • Grade 3 increased total bilirubin without concurrent increased AST/ALT
    • Withhold until recovery to baseline total bilirubin
    • If recovered to baseline ≤7 days, resume at reduced dose; otherwise, permanently discontinue
  • Permanently discontinue
    • Grade 4 increased ALT/AST without increased total bilirubin
    • ALT/AST >3x ULN with total bilirubin >2x ULN without cholestasis or hemolysis
    • Grade 4 increased total bilirubin without concurrent increased AST/ALT

Other adverse reactions

  • Grade 2: Maintain dose; if intolerable, consider withholding until resolved, then resume at reduced dose
  • Grade 3: Withhold until resolved, then resume at reduced dose
  • Grade 4: Permanently discontinue

Renal impairment

  • Mild-to-moderate (CrCl 30-89 mL/min): No dosage adjustment necessary
  • Severe (CrCl <30 mL/min): Recommended dose not established

Hepatic impairment

  • Mild-to-moderate (Child-Pugh Class A or B): No dosage adjustment necessary
  • Severe (Child-Pugh Class C): Pharmacokinetics and safety not studied

Dosing Considerations

Verify pregnancy status in females of reproductive potential before initiating

Patient selection

  • Select patients for treatment based on presence of METex14 skipping alterations in tumor biopsy specimen or plasma (if tumor biopsy cannot be obtained)
  • If alterations are undetected in plasma, re-evaluate the feasibility of tumor biopsy
  • An FDA-approved test for detection of METex14 skipping alteration is not available

Safety and efficacy not established

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Interactions

Interaction Checker

and tepotinib

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            All grades

            • Decreased albumin (76%)
            • Edema (70%)
            • Increased creatinine (55%)
            • Increased alkaline phosphatase (50%)
            • Decreased lymphocytes (48%)
            • Increased ALT (44%)
            • Increased AST (35%)
            • Decreased sodium (31%)
            • Fatigue (27%)
            • Nausea (27%)
            • Decreased hemoglobin (27%)
            • Diarrhea (26%)
            • Increased potassium (25%)
            • Increased gamma-glutamyltransferase (24%)
            • Musculoskeletal pain (24%)
            • Increased amylase (23%)
            • Decreased leukocytes (23%)
            • Dyspnea (20%)
            • Decreased appetite (16%)
            • Cough (15%)
            • Abdominal pain (16%)
            • Constipation (16%)
            • Vomiting (13%)
            • Pleural effusion (13%)
            • Pneumonia (11%)

            Grade 3 to 4

            • Decreased lymphocytes (11%)

            1-10%

            All grades

            • ILD/pneumonitis (<10%)
            • Rash (<10%)
            • Fever (<10%)
            • Dizziness (<10%)
            • Pruritus (<10%)
            • Headache (<10%)

            Grade 3 to 4

            • Decreased albumin (9%)
            • Decreased sodium (8%)
            • Pleural effusion (5%)
            • Increased gamma-glutamyltransferase (5%)
            • Increased amylase (4.6%)
            • Increased ALT (4.1%)
            • Pneumonia (3.9%)
            • Increased AST (2.5%)
            • Musculoskeletal pain (2.4%)
            • Decreased hemoglobin (2%)
            • Dyspnea (2%)
            • Increased alkaline phosphatase (1.6%)
            • Increased potassium (1.6%)
            • Vomiting (1.2%)
            • Decreased appetite (1.2%)

            <1%

            Grade 3 to 4

            • Nausea (0.8%)
            • Abdominal pain (0.8%)
            • Decreased leukocytes (0.8%)
            • Increased creatinine (0.4%)
            • Diarrhea (0.4%)
            • Cough (0.4%)
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            Warnings

            Contraindications

            None

            Cautions

            ILD/pneumonitis, which can be fatal, occurred; monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (eg, dyspnea, cough, fever)

            Fetal harm may occur when administered to pregnant females

            Hepatoxicity

            • Hepatoxicity reported
            • Median time to onset of Grade ≥3 was 30 days
            • Monitor liver function tests (eg, AST, ALT, total bilirubin) before initiation, q2weeks during the first 3 months, then monthly or as clinically indicated
            • More frequent testing if increased AST/ALT or bilirubin develops

            Drug interaction overview

            Inhibits P-gp; substrate of CYP3A4, CYP2C8, and P-gp

            Effects of strong CYP3A4 or P-gp inhibitors and CYP3A4 inducers on tepotinib have not been studied clinically

            • Dual strong CYP3A4 and P-gp inhibitors
              • Avoid coadministration
              • Data suggest drugs that strongly inhibit both CYP3A4 and P-gp may increase tepotinib exposure and risk of toxicities
            • Strong CYP3A4 inducers
              • Avoid coadministration
              • Data suggest drugs that are strong CYP3A4 inducers may decrease exposure and efficacy of tepotinib
            • Certain P-gp substrates
              • Avoid coadministration with P-gp substrates where minimal concentration changes may lead to serious or life-threatening toxicities
              • Tepotinib may increases concentration levels and risk of toxicities of P-gp substrates
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            Pregnancy & Lactation

            Pregnancy

            Based on animal studies and mechanism of action, fetal harm may occur when administered to pregnant females

            Data are unavailable on use in pregnant females

            Verify pregnancy status in females of reproductive potential before initiation

            Animal data

            • Oral administration to pregnant rabbits during organogenesis resulted in malformation (teratogenicity) and anomalies at maternal exposures less than human exposure based on AUC at 450 mg daily
            • Advise pregnant females of potential risk to fetus

            Contraception

            • Females of reproductive potential: Use effective contraception during treatment and for 1 week after final dose
            • Male partners with female partners of reproductive potential: Use effective contraception during treatment and for 1 week after final dose

            Lactation

            There are no data regarding tepotinib or its metabolites in human milk, its effects on breastfed infants, or milk production

            Advise females not to breastfeed during treatment and for 1 week after final dose

            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

            MET tyrosine kinase inhibitor

            Selectively binds to MET tyrosine kinase and disrupts MET and hepatocyte growth factor (HGF)–dependent signal transduction pathways, which may induce apoptosis in tumor cells overexpressing this kinase

            Absorption

            Peak plasma concentration (steady-state): 1,291 ng/mL

            Peak plasma time: 8 hr

            AUC: 27,438 ng⋅hr/mL

            Absolute bioavailability: 71.6%

            Effect of food

            • Mean AUC increased by 1.6-fold and peak plasma concentration increased by 2-fold following a high-fat, high-calories meal (~800-1,000 calories, 150 calories [protein], 250 calories [carbohydrates], and 500-600 calories [fat])
            • Median peak plasma time shifted from 12 hr to 8 hr

            Distribution

            Vd: 1,038 L

            Protein bound: 98%

            Metabolism

            Primarily metabolized by CYP3A4 and CYP2C8

            Major metabolite: M506

            Elimination

            Clearance: 23.8 L/hr

            Half-life: 32 hr

            Excretion

            • Tepotinib: Feces (45% unchanged); urine (13.6% [7% unchanged])
            • M506 (metabolite): 40.4% in plasma
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            Administration

            Oral Administration

            Take at same time every day with food

            Swallow tablets whole; do not chew, crush, or split

            Missed dose

            • ≥8 hr from next scheduled dose: Take as soon as possible
            • <8 hr from next scheduled dose: Skip dose and take next dose at regular scheduled time
            • Vomited dose: Skip dose and take next dose at regular scheduled time

            Storage

            Store at 20-25ºC (68-77ºF); excursion permitted to 15-30ºC (59-86ºF)

            Store in original package

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            Formulary

            FormularyPatient Discounts

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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.
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            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
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            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the 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.