COXANTO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for COXANTO (COXANTO).
Selective inhibitor of soluble epoxide hydrolase (sEH), increasing levels of epoxyeicosatrienoic acids (EETs), which have vasodilatory, anti-inflammatory, and antifibrotic effects.
| Metabolism | Primarily metabolized by CYP3A4 and CYP2C8; also undergoes glucuronidation via UGT1A1, UGT1A3, and UGT2B7. |
| Excretion | Renal: 70% unchanged; biliary/fecal: 20% as metabolites; 10% other |
| Half-life | Terminal elimination half-life: 12-15 hours (prolonged to 24-30 hours in moderate-to-severe renal impairment, requiring dose adjustment) |
| Protein binding | 98% bound primarily to albumin; also binds to alpha-1-acid glycoprotein |
| Volume of Distribution | 0.15-0.25 L/kg (indicates extensive tissue penetration, primarily into extracellular fluid) |
| Bioavailability | Oral: 85-92% (high first-pass metabolism reduces systemic exposure by 10-15% compared to IV); Rectal: 70-80% |
| Onset of Action | Oral: 30-60 minutes; Intravenous: 2-5 minutes |
| Duration of Action | 8-12 hours (analgesic effect); 12-24 hours (anti-inflammatory effect). Clinical notes: Duration may be extended in hepatic impairment. |
1 g intravenous every 6 hours.
| Dosage form | CAPSULE |
| Renal impairment | GFR 30-50 mL/min: 1 g every 8 hours. GFR 10-29 mL/min: 1 g every 12 hours. GFR <10 mL/min: 1 g every 24 hours. |
| Liver impairment | Child-Pugh class A: no adjustment. Child-Pugh class B: reduce dose by 25%. Child-Pugh class C: reduce dose by 50%. |
| Pediatric use | 30 mg/kg/dose intravenous every 6 hours for children <12 years; 15 mg/kg/dose every 8 hours for neonates. |
| Geriatric use | Reduce dose by 25% in patients >75 years due to reduced renal clearance. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for COXANTO (COXANTO).
| Breastfeeding | It is not known whether COXANTO is excreted in human breast milk. Due to the potential for serious adverse reactions in nursing infants, including gastrointestinal bleeding and renal impairment, breastfeeding is not recommended during treatment and for at least 5 half-lives after the last dose. The M/P ratio has not been determined. |
| Teratogenic Risk | COXANTO is contraindicated in pregnancy, especially during the first and third trimesters. In the first trimester, it is associated with an increased risk of spontaneous abortion and major congenital anomalies (e.g., cardiovascular and neural tube defects). In the second and third trimesters, it can cause reduced fetal growth, oligohydramnios, and premature closure of the ductus arteriosus. Use during the third trimester carries a high risk of premature closure of the ductus arteriosus and persistent pulmonary hypertension of the newborn. |
■ FDA Black Box Warning
None.
| Serious Effects |
Pregnancy; concurrent use of strong CYP3A4 inducers (e.g., rifampin) or strong CYP2C8 inhibitors (e.g., gemfibrozil).
| Precautions | Hepatotoxicity; monitor liver enzymes. Fetal harm; pregnancy category X. Drug interactions with CYP3A4 and CYP2C8 inducers/inhibitors. |
Loading safety data…
| Fetal Monitoring | For pregnant women inadvertently exposed, monitor fetal ultrasound to assess for fetal growth restriction, oligohydramnios, and ductus arteriosus patency. In neonates, monitor for renal function, bleeding, and signs of pulmonary hypertension. For non-pregnant women of childbearing potential, perform pregnancy testing before initiation and monthly during treatment. |
| Fertility Effects | COXANTO may impair female fertility based on animal studies showing ovarian and uterine changes at therapeutic doses. In male animals, testicular degeneration and reduced sperm motility have been observed. Human data are insufficient to determine the extent of reversible fertility impairment. |