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Indication and Important Safety Information

Indication

LYRFIGTU™ (lirafugratinib) is indicated for the treatment of adult patients with previously treated, unresectable, locally advanced or metastatic cholangiocarcinoma harboring a FGFR2 fusion or other rearrangement.

Important Safety Information

Warnings and Precautions

Ocular Toxicity

LYRFIGTU can cause retinal pigment epithelial detachment (RPED), which may cause symptoms such as blurred vision.

Among 385 patients who received LYRFIGTU, RPED occurred in 31% of patients, including Grade 3 events in 1.8%. The median time to first onset was 57 days. RPED led to dose interruption in 15% of patients and dose reduction in 10%.

Perform a comprehensive ophthalmological examination, including OCT of the macula, prior to initiation of therapy, every 2 months for the first 13 months, and every 4 months thereafter. For onset of visual symptoms, obtain ophthalmologic evaluation urgently, with follow-up every 3 weeks until resolution or discontinuation of LYRFIGTU. Withhold, reduce the dose, or discontinue LYRFIGTU based on severity.

Among 385 patients who received LYRFIGTU, blurred vision occurred in 18% of patients with Grade 3 events in 1.3% of patients.

Dry eye occurred in 38% of patients. Treat patients with ocular demulcents as needed.

Among 385 patients who received LYRFIGTU, corneal toxicity/keratitis occurred in 11% of patients. Treat patients with ocular demulcents as needed.

Hyperphosphatemia and Soft Tissue Mineralization

LYRFIGTU can cause hyperphosphatemia leading to soft tissue mineralization, calcinosis, nonuremic calciphylaxis, and vascular calcification.

Hyperphosphatemia occurred in 21% of patients. The median time to onset was 15 days. Hyperphosphatemia led to dose interruption in one (0.3%) patient and no permanent discontinuation. Monitor serum phosphate throughout treatment and manage as clinically appropriate.

Embryo-Fetal Toxicity

Based on its mechanism of action and findings from animal studies, LYRFIGTU can cause fetal harm or loss of pregnancy when administered to a pregnant woman.

Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for 6 months after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose.

Adverse Reactions

Serious adverse reactions occurred in 32% of patients. Serious adverse reactions reported in ≥2% of patients were infection (6%), pneumonia (3.4%), fatigue (2.6%) and hemorrhage (2.6%). A fatal adverse reaction of hemorrhage occurred in one patient.

The most common adverse reactions (≥20%) were: Nail toxicity (89%), Stomatitis (80%), Palmar-plantar erythrodysesthesia syndrome (82%), Alopecia (66%), Dry mouth (50%), Dry eye (53%), Fatigue (43%), Dysgeusia (39%), Constipation (37%), Retinal pigment epithelial detachment (38%), Dry skin (37%), infection (34%), rash (34%), abdominal pain (28%), hemorrhage (22%), blurred vision (22%), diarrhea (22%), musculoskeletal pain (22%), nausea (21%), Decreased appetite (20%).

The most common laboratory abnormalities (≥20) were increased phosphate, increased alanine aminotransferase, increased creatinine, decreased hemoglobin, decreased sodium, decreased lymphocytes, increased blood bilirubin, increased aspartate aminotransferase, decreased platelets, increased glucose, decreased leukocytes, increased alkaline phosphatase, decreased albumin, decreased phosphate, decreased neutrophils, decreased bicarbonate.

Drug Interactions

Avoid concomitant use with strong or moderate CYP3A inducers. Avoid concomitant use with strong CYP3A inhibitors. If unavoidable, reduce the LYRFIGTU dose.

Monitor for increased adverse reactions for P-gp, BCRP, OATP1B1, and/or OATP1B3 substrates. Follow the recommended dosage modifications in the approved prescribing information for these substrates.

Other Considerations

Advise women not to breastfeed during treatment and for 1 week after the last dose of LYRFIGTU.

The safety and efficacy of LYRFIGTU have not been established in pediatric patients.

Based on available data, no overall differences in safety or effectiveness of LYRFIGTU have been observed between patients 65 years of age or older and younger adult patients.

No dosage modifications are recommended for patients with mild (Child-Pugh Class A) or moderate (Child-Pugh Class B) hepatic impairment.

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You are encouraged to report negative side effects of prescription drugs to the FDA. Visit www.FDA.gov/medwatch or call 1-800-FDA-1088. You may also report side effects to Elevar Therapeutics at 1-866-4ELEVAR.

Please see the LYRFIGTU full Prescribing Information for additional Important Safety Information.