futibatinib (Rx)

Brand and Other Names:Lytgobi
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 4mg

Cholangiocarcinoma

Indicated for previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma in adults harboring fibroblast growth factor receptor 2 (FGFR2) gene fusions or other rearrangements

20 mg PO qDay

Continue until disease progression or unacceptable toxicity occurs

Dosage Modifications

Dose reductions for adverse reactions

  • First dose reduction: 16 mg qDay
  • Second dose reduction: 12 mg qDay
  • Unable to tolerate 12 mg/day: Permanently discontinue

Retinal pigment epithelial detachment (RPED)

  • Continue at current dose and continue periodic ophthalmic evaluation
  • If RPED resolves in ≤14 days, continue at current dose
  • If not resolving in ≤14 days, withhold; once resolved, resume at previous or lower dose

Hyperphosphatemia

  • Serum phosphate ≥5.5 to ≤7 mg/dL: Continue at current dose and initiate phosphate-lowering therapy; monitor serum phosphate weekly
  • Serum phosphate >7 to ≤10 mg/dL
    • Initiate or adjust phosphate-lowering therapy; monitor serum phosphate weekly
    • Reduce dose to next level
    • If serum phosphate is ≤7 mg/dL within 2 weeks after dose reduction, continue at this reduced dose
    • If serum phosphate is >7 mg/dL within 2 weeks, further reduce dose to the next lower level
    • If serum phosphate is >7 mg/dL within 2 weeks after second dose reduction, withhold until serum phosphate is ≤7 mg/dL and resume at dose before suspending
  • Serum phosphate >10 mg/dL
    • Initiate or adjust phosphate lowering therapy and monitor serum phosphate weekly
    • Withhold until phosphate is ≤7 mg/dL and resume at next lower dose
    • Permanently discontinue if serum phosphate is >7 mg/dL within 2 weeks following 2 dose interruptions and reductions

Other adverse reactions

  • Grade 3: Withhold until toxicity resolves to Grade 1 or baseline
  • Resume for hematologic toxicities resolving ≤1 week, at dose before suspending
  • Resume for other adverse reactions at next lower dose
  • Grade 4: Permanently discontinue

Renal impairment

  • Mild to moderate (creatinine clearance [CrCl] 30-89 mL/min): No dosage adjustment necessary
  • Severe (CrCl 15- 29 mL/min), renal dialysis in end-stage renal disease (CrCl <15 mL/min): Not studied

Hepatic impairment

  • Mild (total bilirubin ≤ULN and AST> ULN, or total bilirubin ≤1.5x ULN and any AST): No dosage adjustment necessary
  • Moderate or severe (total bilirubin >1.5x ULN and any AST): Not studied

Dosing Considerations

Verify pregnancy status of females of reproductive potential before initiating

Patient selection

  • Select for treatment based on presence of an FGFR2 gene fusion or rearrangement
  • An FDA-approved test for detecting FGFR2 gene fusions or other rearrangements is not available

Safety and efficacy not established

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Interactions

Interaction Checker

and futibatinib

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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             activity indicator 

            Contraindicated (0)

              Serious - Use Alternative (15)

              • apalutamide

                apalutamide will decrease the level or effect of futibatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of futibatinib with drugs that are dual P-gp and strong CYP3A inducers may decrease futibatinib efficacy.

              • carbamazepine

                carbamazepine will decrease the level or effect of futibatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of futibatinib with drugs that are dual P-gp and strong CYP3A inducers may decrease futibatinib efficacy.

              • clarithromycin

                clarithromycin will increase the level or effect of futibatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of futibatinib with drugs that are dual P-gp and strong CYP3A inhibitors may increase incidence/severity of futibatinib toxicities.

              • cobicistat

                cobicistat will increase the level or effect of futibatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of futibatinib with drugs that are dual P-gp and strong CYP3A inhibitors may increase incidence/severity of futibatinib toxicities.

              • elvitegravir/cobicistat/emtricitabine/tenofovir DF

                elvitegravir/cobicistat/emtricitabine/tenofovir DF will increase the level or effect of futibatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of futibatinib with drugs that are dual P-gp and strong CYP3A inhibitors may increase incidence/severity of futibatinib toxicities.

              • fosphenytoin

                fosphenytoin will decrease the level or effect of futibatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of futibatinib with drugs that are dual P-gp and strong CYP3A inducers may decrease futibatinib efficacy.

              • itraconazole

                itraconazole will increase the level or effect of futibatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of futibatinib with drugs that are dual P-gp and strong CYP3A inhibitors may increase incidence/severity of futibatinib toxicities.

              • ketoconazole

                ketoconazole will increase the level or effect of futibatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of futibatinib with drugs that are dual P-gp and strong CYP3A inhibitors may increase incidence/severity of futibatinib toxicities.

              • levoketoconazole

                levoketoconazole will increase the level or effect of futibatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of futibatinib with drugs that are dual P-gp and strong CYP3A inhibitors may increase incidence/severity of futibatinib toxicities.

              • nirmatrelvir/ritonavir

                nirmatrelvir/ritonavir will increase the level or effect of futibatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of futibatinib with drugs that are dual P-gp and strong CYP3A inhibitors may increase incidence/severity of futibatinib toxicities.

              • phenytoin

                phenytoin will decrease the level or effect of futibatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of futibatinib with drugs that are dual P-gp and strong CYP3A inducers may decrease futibatinib efficacy.

              • posaconazole

                posaconazole will increase the level or effect of futibatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of futibatinib with drugs that are dual P-gp and strong CYP3A inhibitors may increase incidence/severity of futibatinib toxicities.

              • rifampin

                rifampin will decrease the level or effect of futibatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of futibatinib with drugs that are dual P-gp and strong CYP3A inducers may decrease futibatinib efficacy.

              • ritonavir

                ritonavir will increase the level or effect of futibatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of futibatinib with drugs that are dual P-gp and strong CYP3A inhibitors may increase incidence/severity of futibatinib toxicities.

              • tucatinib

                tucatinib will increase the level or effect of futibatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Avoid or Use Alternate Drug. Coadministration of futibatinib with drugs that are dual P-gp and strong CYP3A inhibitors may increase incidence/severity of futibatinib toxicities.

              Monitor Closely (0)

                Minor (0)

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                  Adverse Effects

                  >10%

                  All grades

                  • Increased phosphate (97%)
                  • Increased creatinine (58%)
                  • Decreased hemoglobin (52%)
                  • Increased glucose (52%)
                  • Increased calcium (51%)
                  • Decreased sodium (51%)
                  • Decreased phosphate (50%)
                  • Increased ALT (50%)
                  • Increased alkaline phosphatase (47%)
                  • Increased AST (46%)
                  • Nail toxicity (47%)
                  • Decreased lymphocytes (46%)
                  • Musculoskeletal pain (43%)
                  • Decreased platelets (42%)
                  • Constipation (39%)
                  • Diarrhea (39%)
                  • Fatigue (37%)
                  • Increased activated partial thromboplastin time (36%)
                  • Dry mouth (35%)
                  • Alopecia (34%)
                  • Decreased leukocytes (33%)
                  • Decreased neutrophils (31%)
                  • Decreased albumin (31%)
                  • Increased creatine kinase (31%)
                  • Stomatitis (30%)
                  • Abdominal pain (30%)
                  • Dry skin (29%)
                  • Increased bilirubin (28%)
                  • Arthralgia (25%)
                  • Dry eye (25%)
                  • Dysgeusia (25%)
                  • Decreased glucose (25%)
                  • Increased prothrombin international normalized ratio (25%)
                  • Decreased glucose (25%)
                  • Nausea (24%)
                  • Decreased appetite (23%)
                  • Urinary tract infection (23%)
                  • Decreased potassium (22%)
                  • Palmoplantar erythrodysesthesia syndrome (21%)
                  • Vomiting (20%)
                  • Weight decreased (18%)
                  • Increased potassium (16%)

                  Grade 3 or 4

                  • Increased phosphate (39%)
                  • Decreased phosphate (20%)
                  • Decreased sodium (15%)
                  • Increased AST (13%)

                  1-10%

                  Grade 3 or 4

                  • Decreased lymphocytes (10%)
                  • Fatigue (8%)
                  • Increased activated partial thromboplastin time (8%)
                  • Increased ALT (7%)
                  • Stomatitis (6%)
                  • Decreased hemoglobin (6%)
                  • Increased creatine kinase (5%)
                  • Palmoplantar erythrodysesthesia syndrome (4.9%)
                  • Increased alkaline phosphatase (4.9%)
                  • Increased glucose (4.9%)
                  • Musculoskeletal pain (3.9%)
                  • Weight decreased (3.9%)
                  • Abdominal pain (2.9%)
                  • Decreased appetite (2.9%)
                  • Urinary tract infection (2.9%)
                  • Decreased albumin (2.4%)
                  • Decreased potassium (2.1%)
                  • Increased potassium (2%)
                  • Nail toxicity (1.9%)
                  • Nausea (1.9%)
                  • Decreased neutrophils (1.6%)
                  • Increased calcium (1.2%)
                  • Decreased leukocytes (1.1%)
                  • Diarrhea (1%)
                  • Vomiting (1%)
                  • Dry eye (1%)
                  • Decreased platelets (1%)
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                  Warnings

                  Contraindications

                  None

                  Cautions

                  Based on animal findings and its mechanism of action, fetal harm may occur in pregnant females

                  Hyperphosphatemia

                  • May cause hyperphosphatemia leading to soft tissue mineralization, calcinosis, nonuremic calciphylaxis, and vascular calcification
                  • Increased phosphate levels are a pharmacodynamic effect of futibatinib
                  • Monitor for hyperphosphatemia throughout treatment
                  • Initiate low phosphate diet and phosphate lowering therapy when serum phosphate level is ≥5.5 mg/dL
                  • For serum phosphate levels is >7 mg/dL, initiate or intensify phosphate lowering therapy and reduce dose, withhold, or permanently discontinue based on duration and severity of hyperphosphatemia

                  Retinal pigment epithelial detachment (RPED)

                  • May cause RPED; symptoms include blurred vision
                  • Perform comprehensive ophthalmologic examination, including optical coherence tomography (OCT) of macula, before initiating, every 2 months for first 6 months, and every 3 months thereafter
                  • For onset of visual symptoms, refer for ophthalmologic evaluation urgently, with follow-up every 3 weeks until it resolves or therapy
                  • Dry eye also occurred; treat with ocular demulcents as needed

                  Drug interaction overview

                  • Substrate of CYP3A and P-glycoprotein (P-gp)
                  • Inhibitor of P-gp and breast cancer resistance protein (BCRP)
                  • Dual P-gp and strong CYP3A inhibitors
                    • Avoid coadministration
                    • Drugs that are dual P-gp and strong CYP3A inhibitors may increase futibatinib exposure and increase risk of adverse reactions
                  • Dual P-gp and strong CYP3A inducers
                    • Avoid coadministration
                    • Dual P-gp and strong CYP3A inducers may decrease futibatinib exposure and efficacy
                  • P-gp or BCRP substrates
                    • Consider more frequent monitoring for adverse reactions associated with sensitive P-gp or BCRP substrates and reduce dose of these drugs per their prescribing information
                    • Futibatinib may increase exposure of drugs that are substrates of P-gp or BCRP
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                  Pregnancy & Lactation

                  Pregnancy

                  Based on an animal study and its mechanism of action, fetal harm or loss of pregnancy may occur when administered to pregnant females

                  There are no available data on use of futibatinib in pregnant females

                  Verify pregnancy status of females of reproductive potential before initiating

                  Contraception

                  • Females of reproductive potential: Use effective contraception during treatment and for 1 week after last dose
                  • Males with female partners of reproductive potential or who are pregnant: Use effective contraception during treatment and for 1 week after last dose

                  Animal data

                  • Oral futibatinib administered to pregnant rats during organogenesis at maternal plasma exposures below human exposure at clinical dose of 20 mg resulted in fetal malformations, fetal growth retardation, and embryofetal death
                  • Advise pregnant females of potential risk to fetus

                  Lactation

                  There are no data on the presence of futibatinib or its metabolites in human milk or their effects on either breastfed infants or milk production

                  Advise women not to breastfeed during treatment and for 1 week after last 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

                  Small molecule kinase inhibitor of FGFR 1, 2, 3, and 4 covalently binds FGFR

                  Constitutive FGFR signaling can support the proliferation and survival of malignant cells

                  Inhibits FGFR phosphorylation and downstream signaling and decreases cell viability in cancer cell lines with FGFR alterations, including FGFR fusions/rearrangements, amplifications, and mutations

                  Absorption

                  Peak plasma concentration: 144 ng/mL

                  Peak plasma time: 2 hr

                  AUC at steady state: 790 ng⋅hr/mL

                  Accumulation: None after repeat doses

                  Effect of food

                  • High-fat and high-calorie meal (900-1000 calories [50% of total caloric content from fat]): Decreases futibatinib AUC by 11% and peak plasma concentration by 42% in healthy subjects

                  Distribution

                  Vd: 66 L

                  Protein bound: 95% bound to human plasma protein, primarily to albumin and α1-acid glycoprotein

                  Metabolism

                  Primarily metabolized by CYP3A and CYP2C9 and CYP2D6 (lesser extent)

                  Elimination

                  Clearance: 20 L/hr

                  Half-life: 2.9 hr

                  Excretion: Feces 91%; urine 9%

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                  Administration

                  Oral Administration

                  Take with or without food at around the same time each day

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

                  Missed dose >12 hr or vomited dose: Resume dosing with next scheduled dose

                  Storage

                  Tablets: Store at room temperature 20-25ºC (68-77ºF), excursions permitted to 15-30ºC (59-86ºF)

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                  Images

                  No images available for this drug.
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                  Patient Handout

                  A Patient Handout is not currently available for this monograph.
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                  Formulary

                  FormularyPatient Discounts

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                  • 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.
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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.