Version May 2024
Cholangiocarcinoma, intrahepatic, previously treated, unresectable locally advanced or metastatic, with FGFR2 gene fusion or rearrangement: Oral: 20 mg once daily until disease progression or unacceptable toxicity (Ref).
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
Missed doses: If a dosed is missed for >12 hours (or if vomiting occurs), resume futibatinib dosing with the next scheduled dose.
Note: Renal function estimated using the Cockcroft-Gault equation.
CrCl ≥30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling; however, no clinically meaningful difference in futibatinib systemic exposure was observed with CrCl 30 to 89 mL/minute.
CrCl<30 mL/minute: There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
End-stage renal disease on dialysis (CrCl <15 mL/minute): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Mild impairment (total bilirubin ≤ ULN and AST > ULN, or total bilirubin >1 to 1.5 times ULN and any AST): There are no dosage adjustments provided in the manufacturer’s labeling; however, no clinically meaningful difference in futibatinib systemic exposure was observed in mild hepatic impairment.
Moderate or severe impairment (total bilirubin >1.5 times ULN and any AST): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
|
Dose levels |
Recommended dose |
|---|---|
|
Initial starting dose |
20 mg once daily |
|
First dose reduction |
16 mg once daily |
|
Second dose reduction |
12 mg once daily |
|
Permanently discontinue futibatinib if unable to tolerate 12 mg once daily. | |
|
Adverse reaction |
Severity |
Futibatinib dosage modification |
|---|---|---|
|
Hyperphosphatemia |
Initiate a low phosphate diet when serum phosphate ≥5.5 mg/dL. | |
|
Serum phosphate ≥5.5 to ≤7 mg/dL |
Maintain futibatinib at the 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 futibatinib dose to the next lower dose level. If the serum phosphate resolves to ≤7 mg/dL within 2 weeks after dose reduction, continue futibatinib at the reduced dose. If serum phosphate does not improve to ≤7 mg/dL within 2 weeks after dose reduction, further reduce futibatinib to the next lower dose level. If serum phosphate still does not improve to ≤7 mg/dL within 2 weeks after the second dose reduction, withhold futibatinib until serum phosphate is ≤7 mg/dL, and then resume at the dose used prior to therapy interruption. | |
|
Serum phosphate >10 mg/dL |
Initiate or adjust phosphate lowering therapy. Withhold futibatinib until serum phosphate is ≤7 mg/dL, and then resume at the next lower dose level. Monitor serum phosphate weekly. If serum phosphate does not improve to ≤7 mg/dL within 2 weeks following 2 dose interruptions and reductions, permanently discontinue futibatinib. | |
|
Ocular toxicity: Retinal pigment epithelial detachment (RPED) or dry eye |
Any |
RPED: Continue futibatinib at the current dose; continue periodic ophthalmic evaluation. If RPED is resolving within 14 days, continue futibatinib at the same dose. If RPED is not resolving within 14 days, withhold futibatinib until resolving, then resume at the previous dose or at a lower dose level. Dry eye: May be managed with ocular demulcents as clinically appropriate. |
|
Other adverse reactions |
Grade 3 |
Withhold futibatinib until reaction resolves to grade 1 or baseline. For grade 3 hematologic toxicities resolving within 1 week, resume futibatinib at the dose used prior to therapy interruption. For other grade 3 adverse reactions, resume futibatinib at the next lower dose level. |
|
Grade 4 |
Permanently discontinue futibatinib. | |
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidences are for adults.
>10%:
Cardiovascular: Increased serum creatine kinase (31%)
Dermatologic: Alopecia (34%), nail disease (47%; including nail discoloration, nail dystrophy, nail hypertrophy, nail pigmentation, onychalgia, onychoclasis, onycholysis, onychomadesis, onychomycosis, paronychia), palmar-plantar erythrodysesthesia (21%), xeroderma (29%)
Endocrine & metabolic: Decreased serum albumin (31%), decreased serum glucose (25%), decreased serum phosphate (50%), decreased serum potassium (22%), decreased serum sodium (51%), increased serum calcium (51%), increased serum glucose (52%), increased serum phosphate (97%), increased serum potassium (16%), weight loss (18%)
Gastrointestinal: Abdominal pain (30%), constipation (39%), decreased appetite (23%), diarrhea (39%, including colitis and gastroenteritis; grade 3: 1%), dysgeusia (25%; including ageusia and taste disorder), nausea (24%; grade 3: 2%), stomatitis (30%; grade 3: 6%), vomiting (20%; grade 3: 1%), xerostomia (35%)
Genitourinary: Urinary tract infection (23%)
Hematologic & oncologic: Decreased hemoglobin (52%; grades 3/4: 6%), decreased neutrophils (31%; grades 3/4: 2%), decreased platelet count (42%, grades 3/4: 1%), increased INR (25%), leukopenia (33%; grades 3/4: 1%), lymphocytopenia (46%; grades 3/4: 10%), prolonged partial thromboplastin time (36%, grades 3/4: 8%)
Hepatic: Increased serum alanine aminotransferase (50%), increased serum alkaline phosphatase (47%), increased serum aspartate aminotransferase (46%), increased serum bilirubin (28%)
Nervous system: Fatigue (37%; including asthenia)
Neuromuscular & skeletal: Arthralgia (25%; including arthritis), musculoskeletal pain (43%; serious: 3%)
Ophthalmic: Dry eye syndrome (25%; including keratitis, punctate keratitis, and ulcerative keratitis), retinal pigment epithelium detachment (8%)
Renal: Increased serum creatinine (58%)
1% to 10%:
Gastrointestinal: Biliary obstruction (serious: 3%), gastrointestinal hemorrhage (4%)
Hepatic: Ascites (4%)
Miscellaneous: Fever (4%)
Frequency not defined: Gastrointestinal: Burning sensation of mouth, esophagitis
There are no contraindications listed in the manufacturer's labeling.
Concerns related to adverse effects:
• Hyperphosphatemia: Futibatinib may cause hyperphosphatemia, leading to soft tissue mineralization, calcinosis, nonuremic calciphylaxis, and vascular calcification. Hyperphosphatemia occurred in the majority of patients who received futibatinib. The median time to onset was 5 days (range: 3 to 117 days); phosphate binders were administered to over three-quarters of patients.
• Ocular toxicity: Futibatinib may cause retinal pigment epithelial detachment (RPED); symptoms may include blurred vision. The median time to first onset of RPED was 40 days. Dry eye has also been reported.
Other warnings/precautions:
• Fibroblast growth factor receptor alteration: Select patients for treatment with futibatinib based on the presence of a fibroblast growth factor receptor (FGFR) 2 fusion or rearrangement.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Tablet Therapy Pack, Oral:
Lytgobi (12 MG Daily Dose): 4 mg (21 ea) [contains corn starch]
Lytgobi (16 MG Daily Dose): 4 mg (28 ea) [contains corn starch]
Lytgobi (20 MG Daily Dose): 4 mg (35 ea) [contains corn starch]
No
Tablet Therapy Pack (Lytgobi (12 MG Daily Dose) Oral)
4 mg (per each): $347.60
Tablet Therapy Pack (Lytgobi (16 MG Daily Dose) Oral)
4 mg (per each): $260.70
Tablet Therapy Pack (Lytgobi (20 MG Daily Dose) Oral)
4 mg (per each): $208.56
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Oral: Administer with or without food at approximately the same time each day. Swallow tablets whole; do not crush, chew, split, or dissolve.
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Futibatinib may cause teratogenicity.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
Cholangiocarcinoma, intrahepatic, previously treated, unresectable locally advanced or metastatic: Treatment of previously treated, unresectable, locally advanced or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 gene fusions or other rearrangements in adults.
Futibatinib may be confused with erdafitinib, fedratinib, infigratinib, and pemigatinib.
This medication is in a class the Institute for Safe Medication Practices (ISMP) includes among its list of drug classes which have a heightened risk of causing significant patient harm when used in error.
Substrate of BCRP/ABCG2, CYP2C9 (minor), CYP2D6 (minor), CYP3A4 (minor), P-glycoprotein/ABCB1 (minor); Note: Assignment of Major/Minor substrate status based on clinically relevant drug interaction potential
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors): Futibatinib may increase the serum concentration of BCRP/ABCG2 Substrates (Clinically Relevant with Inhibitors). Risk C: Monitor therapy
CYP3A4 Inducers (Strong): May decrease the serum concentration of Futibatinib. Risk C: Monitor therapy
Erdafitinib: Serum Phosphate Level-Altering Agents may diminish the therapeutic effect of Erdafitinib. Management: Avoid coadministration of serum phosphate level-altering agents with erdafitinib before initial dose increase period based on serum phosphate levels (Days 14 to 21). Risk D: Consider therapy modification
Inducers of CYP3A4 (Moderate) and P-glycoprotein: May decrease the serum concentration of Futibatinib. Risk C: Monitor therapy
Inducers of CYP3A4 (Strong) and P-glycoprotein: May decrease the serum concentration of Futibatinib. Risk X: Avoid combination
Inhibitors of CYP3A4 (Moderate) and P-glycoprotein: May increase the serum concentration of Futibatinib. Risk C: Monitor therapy
Inhibitors of CYP3A4 (Strong) and P-glycoprotein: May increase the serum concentration of Futibatinib. Risk X: Avoid combination
P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors): Futibatinib may increase the serum concentration of P-glycoprotein/ABCB1 Substrates (Narrow Therapeutic Index/Sensitive with Inhibitors). Risk C: Monitor therapy
Verify pregnancy status prior to treatment initiation (in patients who could become pregnant).
Patients who could become pregnant should use effective contraception during therapy and for 1 week after the last futibatinib dose. Patients with partners who could become pregnant should also use effective contraception during therapy and for 1 week after the last dose of futibatinib.
Based on the mechanism of action and data from animal reproduction studies, in utero exposure to futibatinib may cause fetal harm.
It is not known if futibatinib is present in breast milk.
Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is not recommended by the manufacturer during treatment for 1 week after the last dose of futibatinib.
Monitor phosphate level throughout therapy. Verify pregnancy status prior to therapy initiation in patients who could become pregnant. Perform a comprehensive ophthalmological examination (including optical coherence tomography of the macula) prior to therapy initiation, every 2 months for the first 6 months, and every 3 months thereafter; refer for ophthalmologic evaluation promptly for onset of visual symptoms (with follow-up every 3 weeks until resolution or futibatinib discontinuation). Monitor for signs/symptoms of hyperphosphatemia (eg, muscle cramps, numbness, perioral tingling) and ocular toxicity (eg, visual changes or dry eyes). Monitor adherence.
The American Society of Clinical Oncology hepatitis B virus (HBV) screening and management provisional clinical opinion (ASCO [Hwang 2020]) recommends HBV screening with hepatitis B surface antigen, hepatitis B core antibody, total Ig or IgG, and antibody to hepatitis B surface antigen prior to beginning (or at the beginning of) systemic anticancer therapy; do not delay treatment for screening/results. Detection of chronic or past HBV infection requires a risk assessment to determine antiviral prophylaxis requirements, monitoring, and follow-up.
Futibatinib is a selective, irreversible fibroblast growth factor receptor (FGFR) kinase inhibitor that covalently binds to and inhibits FGFR1, FGFR2, FGFR3, and FGFR4 enzyme activity (Goyal 2023). FGFR phosphorylation inhibition results in decreased FGFR-related signaling and decreased cell viability in cell lines expressing FGFR genetic alterations, leading to decreased proliferation and survival of malignant cells.
Distribution: 66 L.
Protein binding: 95%, primarily to albumin and α1-acid glycoprotein.
Metabolism: Primarily hepatic via CYP3A, and to a lesser extent by CYP2C9 and CYP2D6.
Half-life elimination: 2.9 hours.
Time to peak: 2 hours (range: ~1 to 23 hours).
Excretion: Feces: ~91% (<1% unchanged); Urine: 9% (<1% unchanged).
Clearance: 20 L/hour.
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