Futibatinib – Uses, Dosage, Side Effects, Interaction

Futibatinib is an anticancer agent with demonstrated anti-tumour? activity in mouse and rat xenograft models of human tumors with activating FGFR genetic? alterations. Futibatinib is not expected to affect cell lines with no FGFR genomic aberrations. It suppresses the growth of tumors in a dose-dependent manner.

Use in Cancer

Futibatinib is approved to treat:

• Intrahepatic cholangiocarcinoma (cancer that forms in the bile ducts inside the liver) has spread or cannot be removed with surgery. It is used in adults whose cancer has been treated and has an FGFR2 gene fusion or other change in the structure of the FGFR2 gene.

Futibatinib is approved under FDA’s Accelerated Approval Program. As a condition of approval, confirmatory trial(s) must show that it provides a clinical benefit in these patients.

Futibatinib is also being studied in the treatment of other types of cancer.

Contraindications

• Pregnancy and lactation
• Low Amount Of Phosphate In The Blood
• Decreased Blood Platelets
• Low Levels Of A Type Of White Blood Cell Called Neutrophils
• A High Alanine Transaminase Level
• A High Aspartate Transaminase Level
• Detachment Of Retinal Pigment Epithelium
• Severe? renal failure? patient
• Low Amount Of Sodium In The Blood
• Anemia?
• A Decreased Number Of Lymphocytes In The Blood

Dosage?

Strengths: 4mg, 5mg, 20mg

Cholangiocarcinoma of the biliary tract

• Usual dose: 20 mg (five 4 mg tablets) taken orally once daily
• Confirm the presence of an FGFR2 gene fusion or another rearrangement prior to initiation of treatment.
• Treatment is to be continued until disease progression? or unacceptable toxicity occurs. Patients with previously treated, unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 (FGFR2) gene fusions or other rearrangements.

Dose Adjustments

DOSE MODIFICATION FOR ADVERSE REACTIONS:

• First dose reduction: 16 mg (four 4 mg tablets) orally once daily
• Second dose reduction: 12 mg (three 4 mg tablets) orally once daily
• Permanently discontinue this drug if unable to tolerate 12 mg orally once daily.

DOSE MODIFICATION FOR RETINAL PIGMENT EPITHELIAL DETACHMENT (RPED):

• Continue this drug at the current dose and continue periodic ophthalmic evaluation:
• If resolved within 14 days, continue this drug at the current dose.
• If not resolved within 14 days, withhold this drug until resolved; then resume at the previous or a lower dose.

DOSE MODIFICATION FOR HYPERPHOSPHATEMIA:
Serum phosphate 5.5 to 7 mg/dL:

• Continue this drug at the current dose and start with phosphate-lowering therapy.
• Monitor serum phosphate weekly.

Serum phosphate more than 7 to 10 mg/dL:

• Initiate or adjust phosphate lowering therapy and monitor serum phosphate weekly.
• If the serum phosphate resolves to 7 mg/dL or less within 2 weeks after dose reduction, continue at this reduced dose.
• If serum phosphate is not 7 mg/dL or below within 2 weeks, further reduce to the next lower dose.
• If serum phosphate is not 7 mg/dL or below within 2 weeks after the second dose reduction, withhold this drug until serum phosphate is 7 mg/dL or below and resume at the dose prior to suspending.

Serum phosphate more than 10 mg/dL:

• Initiate or adjust phosphate lowering therapy and monitor serum phosphate weekly.
• Withhold this drug until phosphate is 7 mg/dL or below and resume at the next lower dose.
• Permanently discontinue this drug if serum phosphate is not equal to or less than 7 mg/dL within 2 weeks following 2 dose interruptions and reductions.

DOSE MODIFICATION FOR OTHER ADVERSE REACTIONS:
Grade 3:

• Withhold this drug until toxicity resolves to Grade 1 or baseline?, then resume.
• For hematological toxicities that get resolved within 1 week, continue at the dose prior to suspending.
• For other adverse reactions, continue at the next lower dose.

Grade 4:

• Permanently discontinue this drug.

Administration advice:

• Administer this drug with or without food at approximately the same time each day.
• Swallow tablets whole. Do not crush, chew, split, or dissolve tablets.
• If a dose is missed for more than 12 hours or if vomiting? occurs, resume dosing the next day as scheduled.
• Patients should be advised to read FDA-approved patient labeling (Patient Information).
• Patients should be informed about potential adverse reactions of this drug which include ocular toxicity, hyperphosphatemia, and soft tissue mineralization and immediately reach out to a health care professional if any symptoms related to these events develop.
• Patients should use artificial tears or hydrating or lubricating eye gels to prevent or treat dry eyes.
• Inform patients that this drug may cause nail disorders.
• Notify the health care provider if the patient is pregnant or becomes pregnant during treatment.
• Patients should be cognizant of the risk to a fetus and the potential loss of a pregnancy during the treatment with this drug.
• Male and female patients should use an effective method of contraception? throughout treatment with this drug and for 1 week after the last dose of this drug.
• Do not breastfeed during treatment with this drug and for 1 week after the last dose.
• Do not consume grapefruit products during treatment with this drug.
• Patients are advised to inform health care professional about all concomitant medications, including prescription? medicines, over-the-counter drugs, and herbal products.

Side Effects

The Most Common

• change in appearance or color of nails
• muscle pain?
• constipation?
• diarrhea? or loose stools
• feeling tired or weak
• dry mouth
• hair loss
• mouth sore
• stomach area pain?
• dry skin
• joint pain
• changes in taste
• dry eye
• nausea? or vomiting
• decrease in appetite
• difficulty or painful urination, lower back? pain, or fever?
• redness, swelling?, pain or tenderness? on the hands or feet
• dry or inflamed eyes, increased tears, blurred vision?, flashes of light, or seeing black spots
• muscle cramps or numbness or tingling around your mouth

More common

• Bladder pain
• bloody or cloudy urine
• bone or joint pain
• confusion
• constipation
• cracked lips
• diarrhea
• difficult, burning, or painful urination
• difficulty in breathing
• difficulty in swallowing
• dry eyes
• dry mouth
• fever
• frequent urge to urinate
• irregular heartbeats
• loss of appetite
• lower back or side pain
• mood or mental changes
• muscle cramps in the hands, arms, feet, legs, or face
• nausea
• numbness and tingling around the mouth, fingertips, or feet
• painful irritation of the clear front part of the eye
• redness, swelling, or pain of the skin
• scaling of the skin on the hands and feet
• sores, ulcers, or white spots on the lips, tongue, or inside the mouth
• stomach cramps, tenderness, or pain
• swelling, irritation, soreness, or inflammation of the mouth
• tingling of the hands and feet
• ulceration of the skin
• vomiting
• vomiting of blood or material that looks like coffee grounds
• watering of the eyes
• watery or bloody diarrhea
• weakness

Rare

• Black, tarry stools
• bloody stools
• pale skin
• unusual bleeding or bruising
• unusual tiredness or weakness
• Bluish-brownish hands
• change in taste
• difficulty in moving
• lack or loss of strength
• loss of taste
• muscle aches, cramps, pains, or stiffness
• redness or soreness around the fingernails or loosening of the fingernails

Drug Interactions

Pregnancy and Lactation

US FDA pregnancy category: Not assigned

Pregnancy

Based on findings in an animal study and its mechanism of action, LYTGOBI can cause fetal harm or loss of pregnancy when administered to a pregnant woman [see Clinical Pharmacology (12.1)]. There are no available data on the use of LYTGOBI in pregnant women. Oral administration of futibatinib to pregnant rats during the period of organogenesis at maternal plasma exposures below the human exposure at the clinical dose of 20 mg resulted in fetal malformations, fetal growth retardation, and embryo-fetal death (see Data). Advise pregnant
women of the potential risk to a fetus. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in
clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Lactation

There are no data on the presence of futibatinib or its metabolites in human milk or their effects on either the breastfed child or on milk production. Because of the potential for serious adverse reactions from LYTGOBI in breastfed children, advise women not to breastfeed during treatment and for 1 week after the last dose.