TRUSELTIQ
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TRUSELTIQ (TRUSELTIQ).
TRUSELTIQ (infigratinib) is a fibroblast growth factor receptor (FGFR) inhibitor that binds to and inhibits FGFR1, FGFR2, and FGFR3, thereby blocking FGFR-mediated signal transduction pathways, including STAT, MAPK, and PI3K/AKT, leading to reduced tumor cell proliferation and angiogenesis.
| Metabolism | Primarily metabolized by CYP3A4. |
| Excretion | Primarily hepatic metabolism, with <1% excreted unchanged in urine. Fecal excretion accounts for approximately 86% of the administered dose, while renal excretion accounts for about 12%. |
| Half-life | Terminal elimination half-life is approximately 11 hours (range 6.1–19.8 hours), supporting twice-daily dosing. |
| Protein binding | High protein binding: 99.8%, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent volume of distribution (Vd/F) is approximately 33.8 L (0.45 L/kg for a 75 kg individual), indicating moderate distribution into tissues. |
| Bioavailability | Absolute oral bioavailability is approximately 76% (fasted state). Food increases absorption; taking with a high-fat meal increases Cmax and AUC by approximately 2-fold and 1.6-fold, respectively. |
| Onset of Action | Time to reach steady-state is approximately 3 days with twice-daily dosing. Clinical effect (e.g., tumor response) typically observed within weeks of initiation. |
| Duration of Action | Duration of action is related to pharmacokinetic profile; clinical effect persists as long as therapeutic concentrations are maintained. Steady-state is achieved within 3 days, and drug effect wanes upon discontinuation. |
| Molecular Weight | 460.48 |
600 mg orally twice daily with food.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (GFR ≥30 mL/min). Not studied in severe renal impairment (GFR <30 mL/min) or ESRD. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce starting dose to 300 mg orally twice daily. Child-Pugh C: Not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended; pharmacokinetics similar to younger adults. |
| 1st trimester | Based on animal studies and its mechanism of action, TRUSELTIQ (infigratinib) can cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies in pregnant women. Avoid use during the first trimester due to potential teratogenicity. |
| 2nd trimester | Avoid use during the second trimester. If used, pregnancy testing should be performed prior to initiation, and effective contraception should be used during treatment and for at least 1 month after the last dose. |
| 3rd trimester | Avoid use during the third trimester. Potential fetal toxicity outweighs any benefit. Monitor for oligohydramnios if exposure occurs. |
Clinical note
Comprehensive clinical and safety monograph for TRUSELTIQ (TRUSELTIQ).
| Placental transfer | Infigratinib and/or its metabolites are likely to cross the placenta based on its molecular weight (about 460 Da) and animal reproductive toxicity studies showing fetal malformations and death. |
| Breastfeeding |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to infigratinib or any excipients
| Precautions | Ocular toxicity including central serous retinopathy and retinal pigment epithelial detachment; perform ophthalmic examinations prior to treatment, monthly for 6 months, and every 3 months thereafter., Hyperphosphatemia due to FGFR inhibition; monitor serum phosphate levels and manage with phosphate-lowering therapy or dose modifications., Embryo-fetal toxicity; can cause fetal harm, advise females of reproductive potential to use effective contraception during treatment and for 1 month after the last dose. |
| Food/Dietary | Avoid grapefruit and grapefruit juice, Seville oranges, and starfruit as they may increase drug levels. No other food restrictions; may be taken with or without food. |
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| It is not known whether infigratinib is excreted in human milk. Due to the potential for serious adverse reactions in nursing infants, advise women not to breastfeed during treatment and for at least 1 month after the last dose. |
| Lactation Rating | L4 (possibly hazardous) |
| Teratogenic Risk | FDA Pregnancy Category D. First trimester: high risk of major congenital malformations including craniofacial abnormalities, cardiac defects, and neural tube defects based on animal studies. Second and third trimesters: risk of fetal growth restriction, oligohydramnios, and potential fetal demise due to FGFR inhibition affecting placental development. |
| Fetal Monitoring | Baseline and serial fetal ultrasound for growth, amniotic fluid volume, and anatomy. Monitor maternal blood pressure, renal function, and liver function (specifically phosphate metabolism). In third trimester, monitor for oligohydramnios and fetal distress. After delivery, monitor infant for hypophosphatemia and growth parameters. |
| Fertility Effects | Based on animal studies, potential for reduced fertility in females due to ovarian toxicity (follicular atresia). In males, reversible impairment of spermatogenesis. Human data limited; advise reproductive counseling for both sexes. |
| Clinical Pearls | Truseltiq (infigatinib) is an FGFR inhibitor indicated for cholangiocarcinoma with FGFR2 fusions. Monitor for hyperphosphatemia due to FGFR inhibition; manage with phosphate binders and dose adjustments. Ophthalmic exams are required due to risk of retinal pigment epithelial detachment. Avoid strong CYP3A4 inhibitors or inducers; adjust dose with concomitant use. |
| Patient Advice | Take Truseltiq exactly as prescribed, usually once daily with or without food. · Do not crush or chew capsules; swallow whole. · Report any vision changes, such as blurred vision or floaters, immediately. · Inform your doctor if you experience dry eyes, photophobia, or eye pain. · Monitor for signs of hyperphosphatemia: nausea, vomiting, muscle cramps, or confusion. · Avoid grapefruit and Seville oranges during treatment. · Use effective contraception during and for 1 month after last dose. · Do not breastfeed while taking Truseltiq and for 1 month after last dose. · Keep a list of all medications and supplements to share with your doctor. |