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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for LYNKUET (LYNKUET).
| Breastfeeding | No data on presence in human milk. M/P ratio unknown. Potential for serious adverse reactions in breastfed infant; advise against breastfeeding during treatment and for 1 week after last dose. |
| 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. |
■ FDA Black Box Warning
No black box warning.
| Serious Effects |
["None."]
| 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."] |
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| 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. |