PEMAZYRE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PEMAZYRE (PEMAZYRE).
Selective inhibitor of fibroblast growth factor receptor (FGFR) 1, 2, 3, and 4; binds to and inhibits FGFR kinase activity, leading to decreased tumor cell proliferation and angiogenesis.
| Metabolism | Primarily metabolized by CYP3A4 and CYP2D6; minor contribution from CYP1A2 and CYP2C19. |
| Excretion | Primarily hepatobiliary excretion: 72% of the dose recovered in feces (mainly as unchanged drug and metabolites); renal excretion accounts for approximately 17% (less than 1% unchanged). |
| Half-life | Terminal elimination half-life is approximately 20 hours (range 14–32 h), supporting once-daily dosing with steady-state reached within 8 days. |
| Protein binding | 98.5% bound to human plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Geometric mean Vd/F is 107 L (approximately 1.5 L/kg), indicating extensive extravascular distribution. |
| Bioavailability | Absolute bioavailability not determined; after oral administration, peak concentrations achieved at 2–3 hours; minimal food effect (high-fat meal reduces Cmax by 20%, but AUC unchanged). |
| Onset of Action | Not applicable; pemazyre is administered orally for chronic treatment; clinical response (e.g., tumor shrinkage) assessed after weeks to months. |
| Duration of Action | Continuous; plasma concentrations remain above target inhibition levels throughout the dosing interval (24 h) with daily dosing. |
| Molecular Weight | 451.95 |
13.5 mg orally once daily continuously until disease progression or unacceptable toxicity.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment recommended for mild to moderate renal impairment (CrCl 30-89 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease. |
| Liver impairment | For Child-Pugh A: 9 mg orally once daily. Child-Pugh B: 6.5 mg orally once daily. Child-Pugh C: not recommended. |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended for elderly. Use caution due to increased potential for renal and hepatic impairment. |
| 1st trimester | Insufficient human data; based on mechanism of action and animal studies, may cause fetal harm. Avoid use in pregnancy. |
| 2nd trimester | Insufficient human data; based on mechanism of action and animal studies, may cause fetal harm. Avoid use in pregnancy. |
| 3rd trimester | Insufficient human data; based on mechanism of action and animal studies, may cause fetal harm. Avoid use in pregnancy. |
Clinical note
Comprehensive clinical and safety monograph for PEMAZYRE (PEMAZYRE).
| Placental transfer | Based on molecular weight (less than 500 Da) and animal studies, pemigatinib is likely transferred across the placenta. No human placental transfer studies available. |
| Breastfeeding | No human data on presence in breast milk, effects on breastfed infants, or milk production. Due to potential for serious adverse reactions in nursing infants, advise patients not to breastfeed during treatment and for at least 1 week after final dose. |
■ FDA Black Box Warning
Retinal pigment epithelial detachment (RPED) occurred in 25% of patients, including 2% with RPED associated with vision loss or retinal detachment. Monitor for visual symptoms and perform ophthalmologic examination monthly for first 4 months, then every 3 months.
| Serious Effects |
Hypersensitivity to pemigatinib or any excipients
| Precautions | Retinal pigment epithelial detachment, hyperphosphatemia leading to soft tissue mineralization, embryo-fetal toxicity, and risk of QT prolongation. |
| Food/Dietary | Avoid grapefruit, grapefruit juice, and Seville oranges as they inhibit CYP3A4 and may increase pemigatinib levels. |
Loading safety data…
| Lactation Rating | L5 |
| Teratogenic Risk | Pemazyre (pemigatinib) is embryotoxic and teratogenic in animal studies. Based on its mechanism of action (FGFR inhibitor), it is expected to cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies in pregnant women. Advise females of reproductive potential of the potential risk to the fetus. First trimester: High risk for major malformations. Second and third trimesters: Risk of impaired growth and development. |
| Fetal Monitoring | Monitor calcium and phosphate levels regularly due to risk of hyperphosphatemia and related toxicity. Monitor for retinal toxicity (including retinal detachment) and other ocular adverse reactions. Perform ophthalmologic examinations at baseline and periodically. Assess for signs of fetal distress via ultrasound if pregnancy is confirmed. |
| Fertility Effects | Pemigatinib may impair fertility in females of reproductive potential based on animal studies. In males, no specific studies have been reported, but based on mechanism, potential for sperm abnormalities cannot be excluded. |
| Clinical Pearls |
| Pemazyre (pemigatinib) is a fibroblast growth factor receptor (FGFR) inhibitor indicated for cholangiocarcinoma with FGFR2 fusions/rearrangements. Monitor for hyperphosphatemia due to FGFR inhibition; manage with phosphate-lowering therapy or dose interruption/reduction. Check serum phosphate levels within first 2 weeks and regularly thereafter. May cause retinal pigment epithelial detachment (RPED); perform comprehensive ophthalmologic exam at baseline and monthly for first 6 months, then every 3 months. Avoid strong CYP3A4 inducers; use with caution with moderate to strong CYP3A4 inhibitors. |
| Patient Advice | Take pemigatinib exactly as prescribed, usually once daily for 2 weeks on and 1 week off (21-day cycles). · Swallow tablets whole with or without food; do not crush or chew. · Report symptoms of high phosphate levels (muscle cramps, nausea, diarrhea, bone pain) or eye changes (blurred vision, floaters, flashes). · Avoid grapefruit, grapefruit juice, and Seville oranges during treatment. · Use effective contraception during treatment and for 1 week after last dose. · Do not donate blood or blood products during treatment. |