LYNKUET
Clinical safety rating: caution
Comprehensive clinical and safety monograph for LYNKUET (LYNKUET).
Lynkue (pemigatinib) is a selective, potent, oral inhibitor of fibroblast growth factor receptor (FGFR) 1, 2, and 3. It binds to and inhibits FGFR phosphorylation, leading to reduced tumor cell proliferation and angiogenesis in tumors with FGFR alterations.
| Metabolism | Primarily metabolized by CYP3A4; minor contributions from CYP2C8 and CYP2D6. |
| Excretion | Primarily hepatic metabolism via CYP3A4; biliary/fecal excretion accounts for ~90% of the dose (71% as metabolites, 19% as unchanged drug). Renal elimination is minimal, with <1% excreted unchanged in urine. |
| Half-life | Terminal elimination half-life is approximately 60 hours. This long half-life supports once-daily dosing and allows for steady-state concentrations after ~10-12 days. |
| Protein binding | Highly protein bound at ~99.8%, primarily to serum albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 1600 L (not weight-based due to lipophilicity), indicating extensive tissue distribution, particularly into breast and tumor tissues. |
| Bioavailability | Oral bioavailability is not reported separately but absorption is complete, with median time to peak concentration (Tmax) of 2 hours. Food does not significantly affect absorption. |
| Onset of Action | Oral: Clinical effect (reduction in estrogen receptor signaling) begins within 1-2 weeks, with partial response by 4 weeks. |
| Duration of Action | Duration is prolonged due to the long half-life; receptor occupancy persists for days after discontinuation. Therapeutic duration is continuous until disease progression or unacceptable toxicity. |
| Molecular Weight | 563.64 |
28-day cycles: days 1-21, 200 mg orally twice daily.
| Dosage form | CAPSULE |
| Renal impairment | CrCl 30-59 mL/min: 150 mg twice daily; CrCl 15-29 mL/min: 100 mg twice daily; CrCl <15 mL/min or dialysis: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B or C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment; monitor renal function and toxicity more frequently. |
| 1st trimester | Contraindicated due to teratogenicity observed in animal studies; embryofetal lethality and malformations. |
| 2nd trimester | Contraindicated; potential for fetal harm outweighs any benefit. |
| 3rd trimester | Contraindicated; risk of fetal bone marrow suppression and hemorrhage. |
Clinical note
Comprehensive clinical and safety monograph for LYNKUET (LYNKUET).
| Placental transfer | Crosses placenta significantly; found in fetal plasma at concentrations comparable to maternal. |
| Breastfeeding | Excreted in human milk; potential for serious adverse reactions in nursing infants, including bone marrow suppression. Discontinue breastfeeding or discontinue drug, considering importance of drug to mother. |
| Lactation Rating |
■ FDA Black Box Warning
No black box warning.
| Serious Effects |
PregnancyHypersensitivity to active substance or any excipientSevere hepatic impairmentConcomitant use with strong CYP3A4 inducers
| Precautions | Ocular toxicity: Retinal pigment epithelial detachment (RPED) may occur; perform comprehensive ophthalmologic examination at baseline and every 2 months for the first 6 months, then every 3 months thereafter., Hyperphosphatemia: Can cause phosphate elevations; monitor serum phosphate levels and manage with phosphate-lowering therapy as needed., Embryo-fetal toxicity: May cause fetal harm; advise females of reproductive potential of the risk and to use effective contraception. |
| Food/Dietary | Avoid grapefruit, grapefruit juice, and Seville oranges due to potential CYP3A4 inhibition. No other specific food restrictions. |
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| L5 (Contraindicated) |
| Teratogenic Risk | First trimester: Animal studies show teratogenicity; human data insufficient. Potential for major congenital malformations (e.g., cardiovascular, neural tube defects). Avoid use. Second/third trimester: Risk of fetal growth restriction, oligohydramnios, and fetal bradycardia due to pharmacodynamic effects. |
| Fetal Monitoring | Monitor maternal blood pressure and renal function. Serial fetal ultrasound to assess growth and amniotic fluid volume. Fetal heart rate monitoring during labor due to risk of bradycardia. |
| Fertility Effects | Animal studies show impaired fertility (delayed conception, reduced implantation). Human data unavailable. May reduce ovarian function temporarily. |
| Clinical Pearls | LYNKUET (pemigatinib) is a selective FGFR inhibitor. Monitor for hyperphosphatemia as an on-target effect; initiate phosphate-lowering therapy if serum phosphate >5.5 mg/dL. Dose reductions or interruptions may be required for adverse reactions like nail toxicity, stomatitis, fatigue, and serous retinal detachment. Contraindicated with strong CYP3A4 inducers; avoid coadministration. Baseline and periodic ophthalmologic exams are recommended. |
| Patient Advice | Take LYNKUET exactly as prescribed, with or without food. Do not crush or break tablets. · Avoid grapefruit, grapefruit juice, and Seville oranges while taking this medication. · Report new or worsening eye symptoms such as blurred vision, floaters, or visual disturbances immediately. · Inform your doctor if you experience severe nausea, vomiting, diarrhea, or mouth sores. · Use effective contraception during treatment and for at least 1 week after the last dose. · Do not take St. John's wort or any supplements without consulting your healthcare provider. · Attend all scheduled blood tests to monitor phosphate levels and liver function. |