HYRNUO
Clinical safety rating
cautionComprehensive clinical and safety monograph for HYRNUO (HYRNUO).
(E)-2-(((2-(6,7-dimethoxyquinazolin-4-ylamino)phenyl)thio)methyl)-4-methyl-2H-pyrazolo[1,5-a]pyrazin-3(5H)-one is a selective inhibitor of fibroblast growth factor receptor (FGFR) 1, 2, 3, and 4. It binds to the ATP-binding site of FGFR kinases, blocking downstream signaling pathways, including RAS-MAPK-ERK and PI3K-AKT, thereby inhibiting tumor cell proliferation and angiogenesis.
| Metabolism | Primarily metabolized by CYP2C9 and CYP3A4; minor contributions from CYP2C19 and CYP2D6. Forms active metabolites M1 (desmethyl) and M2 (N-oxide). |
| Excretion | Renal excretion of unchanged drug accounts for approximately 60% of elimination; biliary/fecal excretion accounts for 30% (including metabolites), with the remainder eliminated via minor metabolic pathways. |
| Half-life | Terminal elimination half-life is 12-15 hours in adults with normal renal function, supporting twice-daily dosing. |
| Protein binding | 98% bound primarily to albumin. |
| Volume of Distribution | 0.3-0.4 L/kg, indicating distribution into total body water with limited tissue binding. |
| Bioavailability | Oral: 85% (fasting); 60% with high-fat meal (reduced absorption). |
| Onset of Action | Oral: 30-60 minutes; intravenous: 5-10 minutes. |
| Duration of Action | 12-24 hours depending on dose and renal function; may be prolonged in renal impairment. |
| Molecular Weight | 307.33 |
100 mg orally once daily
| Dosage form | TABLET |
| Renal impairment | GFR ≥60 mL/min: No adjustment. GFR 30-59: 50 mg once daily. GFR <30: Not recommended. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: 50 mg once daily. Child-Pugh C: Not recommended. |
| Pediatric use | Not established for patients under 18 years. |
| Geriatric use | No specific dose adjustment; monitor renal function and consider age-related decline. |
| 1st trimester | Insufficient human data; animal studies show risk. Use only if benefit justifies potential risk. |
| 2nd trimester | No controlled studies in pregnant women. Consider risk-benefit. |
| 3rd trimester | Avoid in third trimester due to potential for adverse effects on fetus (e.g., constriction of ductus arteriosus). |
Clinical note
Comprehensive clinical and safety monograph for HYRNUO (HYRNUO).
| Placental transfer | Crosses placenta in humans; documented in amniotic fluid. |
| Breastfeeding | Excreted in breast milk in low amounts; monitor infant for adverse effects. Use with caution. |
| Lactation Rating | L3 |
| Teratogenic Risk | HYRNUO is contraindicated in pregnancy due to demonstrated teratogenicity in animal studies and limited human data. First trimester exposure is associated with major congenital malformations including neural tube defects and cardiovascular anomalies. Second and third trimester exposure may cause fetal growth restriction and oligohydramnios. |
| Fetal Monitoring | Monitor for fetal growth restriction via serial ultrasound. Assess amniotic fluid volume. In neonates, monitor for signs of toxicity (e.g., respiratory depression, hypotonia). |
| Fertility Effects | HYRNUO may impair fertility in females based on animal studies showing disruption of estrous cycles and reduced ovarian function. Reversal of effects after discontinuation has not been established. In males, no data available. |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to drug or any excipientSevere hepatic impairmentPregnancy (third trimester)
| Precautions | Retinal pigment epithelial detachment (RPED) and other visual disturbances: conduct ophthalmic examinations prior to and during treatment, Hyperphosphatemia: monitor serum phosphate levels and manage with phosphate-lowering therapy or dose modification, Non-healing corneal ulcers: requires ophthalmologic evaluation, Embryo-fetal toxicity: can cause fetal harm; advise effective contraception |
| Food/Dietary | No specific food interactions. Grapefruit juice does not significantly affect HYRNUO metabolism. Maintain consistent vitamin K intake if on warfarin; not applicable to HYRNUO. Alcohol may increase bleeding risk; advise moderation. |
| Clinical Pearls | HYRNUO is a novel oral anticoagulant with high specificity for factor Xa. Monitor renal function prior to initiation and periodically; adjust dose if CrCl <30 mL/min. No routine coagulation monitoring required. Reversal agent andexanet alfa is available for life-threatening bleeding. Avoid in patients with mechanical heart valves or moderate-to-severe mitral stenosis. Caution with dual antiplatelet therapy due to increased bleeding risk. |
| Patient Advice | Take HYRNUO exactly as prescribed, usually once daily with or without food. · Do not skip doses; if a dose is missed, take it as soon as remembered on the same day. Do not double the next dose. · Inform all healthcare providers that you are taking HYRNUO, especially before surgery or dental procedures. · Watch for signs of bleeding: unusual bruising, prolonged bleeding from cuts, pink/brown urine, red/black stools, coughing up blood, or vomiting blood. · Avoid aspirin, NSAIDs, or other blood thinners unless prescribed by your doctor. · Keep a list of all medications and supplements you take, as some may interact with HYRNUO. · Store at room temperature away from moisture and heat. Do not stop taking without consulting your doctor. |
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