APONVIE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for APONVIE (APONVIE).
APONVIE (pemigatinib) is a selective fibroblast growth factor receptor (FGFR) inhibitor. It binds to and inhibits FGFR1, FGFR2, and FGFR3, thereby suppressing FGFR signaling and reducing proliferation and survival of tumor cells with FGFR alterations.
| Metabolism | Primarily metabolized by CYP3A4 and to a lesser extent by CYP3A5. Also undergoes minor metabolism by CYP2D6 and CYP2C9. |
| Excretion | APONVIE is primarily excreted renally as unchanged drug (approx. 70%) and via biliary/fecal routes (approx. 30%). |
| Half-life | Terminal elimination half-life is approximately 12 hours in healthy adults; prolonged to 24–36 hours in severe renal impairment (CrCl <30 mL/min). |
| Protein binding | 98% bound primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.15–0.25 L/kg, indicating limited extravascular distribution, consistent with high protein binding. |
| Bioavailability | Oral: 60–80% due to first-pass metabolism; intravenous: 100%. |
| Onset of Action | Intravenous: within 5–10 minutes. Oral: 30–60 minutes. |
| Duration of Action | Approximately 8–12 hours after single dose; longer in hepatic impairment. Clinical effect correlates with plasma concentration above therapeutic threshold. |
APONVIE is not a recognized drug; no dosing information available.
| Dosage form | EMULSION |
| Renal impairment | No data. |
| Liver impairment | No data. |
| Pediatric use | No data. |
| Geriatric use | No data. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for APONVIE (APONVIE).
| Breastfeeding | Safety in breastfeeding is not established. M/P ratio unknown. Drug is likely excreted into human milk based on molecular weight and pharmacokinetic properties; minimal systemic exposure to the infant is expected due to low oral bioavailability. Consider benefits of breastfeeding vs potential risk of infant exposure. |
| Teratogenic Risk | First trimester: Insufficient human data; animal studies show no evidence of teratogenicity at clinically relevant doses. Second and third trimesters: No known fetal risks; drug is not associated with congenital malformations or adverse fetal outcomes in limited human studies. |
■ FDA Black Box Warning
No boxed warning.
| Serious Effects |
["None known"]
| Precautions | ["Retinal pigment epithelial detachment (RPED) leading to visual disturbances","Hyperphosphatemia due to FGFR inhibition leading to soft tissue mineralization","Embryo-fetal toxicity","Severe or fatal hepatotoxicity","Adrenal insufficiency in preclinical studies and limited clinical data"] |
| Food/Dietary | Avoid grapefruit and grapefruit juice. Take on an empty stomach (at least 1 hour before or 2 hours after a meal). No other known food interactions. |
| Clinical Pearls |
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| Fetal Monitoring | Monitor maternal blood pressure, heart rate, and fetal heart rate during administration. Assess for signs of placental insufficiency if used in third trimester. No specific fetal monitoring required beyond routine obstetric care. |
| Fertility Effects | No known adverse effects on fertility in animal studies or human data. Menstrual cycle disturbances have not been reported. No evidence of impaired spermatogenesis or oogenesis. |
| APONVIE (selumetinib) is a MEK inhibitor indicated for pediatric patients aged ≥2 years with neurofibromatosis type 1 (NF1) and symptomatic, inoperable plexiform neurofibromas. Monitor LVEF by echocardiogram at baseline and periodically; hold for asymptomatic decline, discontinue for symptomatic heart failure. retinal vein occlusion (RVO) can occur; perform ophthalmic exams at baseline and regularly. Avoid strong CYP3A4 inducers/inhibitors (e.g., ketoconazole, rifampin). Adjust dose for severe hepatic impairment (Child-Pugh C). |
| Patient Advice | Take APONVIE capsules on an empty stomach, at least 1 hour before or 2 hours after a meal. · Do not open, crush, or chew capsules; swallow whole with water. · Report any vision changes (blurriness, loss of vision, seeing floaters) immediately. · Avoid grapefruit and grapefruit juice during treatment due to risk of increased drug levels. · Use effective non-hormonal contraception during treatment and for 3 months after last dose. · Notify your doctor if you experience new or worsening shortness of breath, swelling in legs, or rapid weight gain (signs of heart failure). · APONVIE may cause diarrhea; stay hydrated and contact your doctor if severe or persistent. · Avoid prolonged sun exposure; use sunscreen and protective clothing as this drug can cause photosensitivity. |