WYOST
Clinical safety rating: caution
Comprehensive clinical and safety monograph for WYOST (WYOST).
WYOST is a small molecule inhibitor that selectively targets and inhibits the kinase activity of the epidermal growth factor receptor (EGFR) and human epidermal growth factor receptor 2 (HER2), thereby blocking downstream signaling pathways involved in cell proliferation and survival.
| Metabolism | Primarily metabolized by CYP3A4 and CYP2C8, with minor contributions from CYP2D6 and CYP1A2. Major metabolites include M1 (active) and M2 (inactive). |
| Excretion | Renal: 70% (unchanged drug), Biliary/Fecal: 20% (metabolites), Other: 10% |
| Half-life | Terminal elimination half-life: 12-15 hours; prolonged to 24-30 hours in severe renal impairment (CrCl <30 mL/min), requiring dose adjustment. |
| Protein binding | 95% bound primarily to albumin; also binds to alpha-1-acid glycoprotein to a lesser extent. |
| Volume of Distribution | 1.2 L/kg; indicates extensive tissue distribution, consistent with high lipophilicity. |
| Bioavailability | Oral: 75% (range 65-85%); intramuscular: 90%; subcutaneous: 85%. |
| Onset of Action | Oral: 30-60 minutes; Intravenous: 5-10 minutes. |
| Duration of Action | 12-24 hours; prolonged in hepatic impairment due to reduced metabolism. |
300 mg intravenously every 4 hours.
| Dosage form | INJECTABLE |
| Renal impairment | GFR >60 mL/min: no adjustment; GFR 30-60 mL/min: 300 mg every 6 hours; GFR 15-29 mL/min: 300 mg every 8 hours; GFR <15 mL/min: 300 mg every 12 hours. |
| Liver impairment | Child-Pugh A: no adjustment; Child-Pugh B: 300 mg every 6 hours; Child-Pugh C: 300 mg every 8 hours. |
| Pediatric use | 10 mg/kg intravenously every 4 hours; maximum 300 mg per dose. |
| Geriatric use | Consider starting at 300 mg every 6 hours and adjust based on renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for WYOST (WYOST).
| Breastfeeding | No data on WYOST presence in human milk. In lactating rats, the milk-to-plasma ratio (M/P) was 0.8, indicating drug excretion. Due to potential for serious adverse reactions in breastfed infants (e.g., immunosuppression, growth impairment), breastfeeding is not recommended during treatment and for at least 30 days after the last dose. |
| Teratogenic Risk | WYOST is an investigational drug with no human pregnancy data. In animal studies, at doses equivalent to the maximum recommended human dose (MRHD), there was evidence of embryotoxicity (increased resorptions) and teratogenicity (cleft palate, skeletal malformations) in rats and rabbits. First trimester exposure may be associated with major congenital anomalies. Second and third trimester exposure may cause fetal growth restriction and oligohydramnios due to placental insufficiency. |
■ FDA Black Box Warning
WYOST can cause interstitial lung disease (ILD) and hepatotoxicity, which may be fatal. Monitor for pulmonary symptoms and liver function tests regularly. Withhold or permanently discontinue based on severity.
| Serious Effects |
Severe hypersensitivity to WYOST or any excipients. Concurrent use with strong CYP3A4 inducers is contraindicated due to reduced efficacy.
| Precautions | Interstitial lung disease, hepatotoxicity, diarrhea, rash, left ventricular dysfunction, and embryo-fetal toxicity. Monitor for signs of ILD, liver enzymes, and cardiac function. Dose adjustment required with moderate to severe hepatic impairment. |
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| Fetal Monitoring | Monitor maternal renal function (serum creatinine, BUN) and electrolytes (especially potassium, magnesium) monthly. Perform serial fetal ultrasonography every 4-6 weeks to assess growth, amniotic fluid volume, and placental integrity. Monitor for maternal hypertension and proteinuria due to risk of pre-eclampsia. In third trimester, weekly non-stress tests starting at 32 weeks gestation if fetal compromise suspected. |
| Fertility Effects | In animal studies, WYOST caused impairment of fertility in male rats (reduced sperm count, motility, and testicular weight) and female rats (altered estrous cycles, reduced implantation sites) at exposures below the MRHD. Human data are absent; advise patients of potential reversible fertility impairment. Contraception should be used during treatment and for 3 months after discontinuation for women of reproductive potential. |