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. |
| Molecular Weight | 287.36 Da |
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 | Contraindicated due to embryotoxicity and teratogenic effects observed in animal studies; may cause fetal malformations. |
| 2nd trimester | Contraindicated due to risk of fetal developmental abnormalities and potential for spontaneous abortion. |
| 3rd trimester | Contraindicated due to risk of neonatal respiratory depression, withdrawal syndrome, and other adverse effects. |
Clinical note
Comprehensive clinical and safety monograph for COXANTO (COXANTO).
| Placental transfer | Extensively crosses the placenta; detectable in fetal plasma within minutes of maternal administration. |
| Breastfeeding | Excreted in human milk; due to potential for serious adverse reactions in nursing infants, including respiratory depression and withdrawal, breast-feeding is not recommended during treatment and for 7 days after last dose. |
■ FDA Black Box Warning
None.
| Serious Effects |
Hypersensitivity to COXANTO or any excipientConcomitant use with MAO inhibitors or within 14 days of discontinuationSevere respiratory depressionAcute or severe bronchial asthmaKnown or suspected gastrointestinal obstructionParalytic ileusPregnancy
| Precautions | Hepatotoxicity; monitor liver enzymes. Fetal harm; pregnancy category X. Drug interactions with CYP3A4 and CYP2C8 inducers/inhibitors. |
| Food/Dietary | No specific food interactions known for canakinumab. Diet does not affect drug absorption as it is administered subcutaneously. Maintain a balanced diet to support immune function. |
| Clinical Pearls |
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| Lactation Rating | L5 (Contraindicated) |
| 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. |
| 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. |
| COXANTO (canakinumab) is a monoclonal antibody targeting IL-1β. Monitor for neutropenia; a fall in absolute neutrophil count <1.0×10^9/L should prompt temporary discontinuation. Live vaccines contraindicated during therapy. Serious hypersensitivity reactions, including anaphylaxis, may occur. Tuberculosis reactivation risk: screen for latent TB before initiation. Neutralizing antibodies may develop, reducing efficacy. |
| Patient Advice | Report any signs of infection (fever, cough, sore throat) promptly, as canakinumab lowers your immune system's ability to fight infections. · Avoid live vaccines (e.g., MMR, shingles) during treatment and for at least 3 months after last dose; discuss vaccination schedule with your doctor. · Notify your healthcare provider if you experience symptoms of an allergic reaction (rash, hives, difficulty breathing, swelling of face/lips/tongue). · Do not stop or change the dosing schedule without consulting your doctor; keep all appointments for subcutaneous injections. · Inform your doctor if you have had tuberculosis or close contact with someone with TB; screening is required before starting therapy. · Pregnancy: use effective contraception and notify prescriber if you become pregnant; breastfeeding not recommended during treatment. |