Dosing & Uses
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
Interactions
Interaction Checker
No Results
Contraindicated
Serious - Use Alternative
Significant - Monitor Closely
Minor
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 (1)
- lenacapavir
lenacapavir will increase the level or effect of futibatinib by affecting hepatic/intestinal enzyme CYP3A4 metabolism. Use Caution/Monitor. Lencapavir may increase CYP3A4 substrates initiated within 9 months after last SC dose of lenacapavir, which may increase potential risk of adverse reactions of CYP3A4 substrates.
Minor (0)
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%)
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
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.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%
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)
Images
Formulary
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