TAVNEOS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TAVNEOS (TAVNEOS).
Avanacor (TAVNEOS) is a selective inhibitor of the 5-lipoxygenase (5-LO) enzyme, which catalyzes the conversion of arachidonic acid to leukotrienes, thereby reducing the production of pro-inflammatory leukotrienes.
| Metabolism | TAVNEOS is primarily metabolized by CYP3A4 and UGT isoforms, with minor contributions from CYP2C9 and CYP2C19. |
| Excretion | Approximately 70% of the dose is excreted in urine as unchanged drug and metabolites (with ~30% as unchanged avacopan), and 30% in feces. Renal elimination is the primary route. |
| Half-life | Terminal elimination half-life is approximately 8-10 hours in healthy subjects. In patients with renal impairment, half-life may be prolonged, but no dose adjustment is required for mild to moderate impairment. |
| Protein binding | Approximately 98-99% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.5 L/kg, indicating distribution primarily in plasma and extracellular fluid. |
| Bioavailability | Absolute bioavailability is not determined; oral absorption is rapid with peak plasma concentrations at 1-3 hours. Food does not significantly affect absorption. |
| Onset of Action | Clinical effect observed within 2 weeks of oral administration. Maximum reduction in proteinuria and stabilization of renal function seen by 4 weeks. |
| Duration of Action | Duration of action extends beyond the dosing interval (twice daily) due to complement blockade persistence. Clinical effects wane within 1-2 weeks after discontinuation. |
10 mg orally twice daily, with or without food.
| Dosage form | CAPSULE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (eGFR ≥30 mL/min/1.73 m²). Not recommended in severe renal impairment (eGFR <30 mL/min/1.73 m²) or end-stage renal disease. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not recommended in moderate (Child-Pugh B) or severe (Child-Pugh C) hepatic impairment. |
| Pediatric use | Safety and efficacy in pediatric patients have not been established; no recommended dosing available. |
| Geriatric use | No specific dose adjustment required; however, consider age-related renal and hepatic function decline, and monitor for adverse effects more frequently. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TAVNEOS (TAVNEOS).
| Breastfeeding | No data are available on the presence of avacopan in human milk, effects on the breastfed infant, or effects on milk production. The molecular weight (about 500 Da) suggests potential for excretion into breast milk. The M/P ratio is unknown. Because of the potential for serious adverse reactions in nursing infants, advise patients that breastfeeding is not recommended during treatment with TAVNEOS and for 2 weeks after the last dose. |
| Teratogenic Risk | TAVNEOS (avacopan) is a complement C5a receptor antagonist. In animal reproduction studies, avacopan was not teratogenic in rats or rabbits at exposures up to 3 times the human AUC at the recommended dose. However, there are no adequate and well-controlled studies in pregnant women. Because animal studies are not always predictive of human response, TAVNEOS should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Based on its mechanism of action, there is no direct evidence of teratogenicity; however, indirect effects due to immunomodulation cannot be excluded. |
■ FDA Black Box Warning
None.
| Serious Effects |
["History of hypersensitivity to avanacor or any component of the formulation.","Severe hepatic impairment (Child-Pugh C)."]
| Precautions | ["Hepatotoxicity: Monitor liver enzymes; discontinue if elevations occur.","Immunosuppression: Increased risk of infections; monitor for signs of infection.","Leukopenia: Monitor white blood cell counts.","Drug interactions: Avoid use with strong CYP3A4 inducers (e.g., rifampin) and reduce dose with strong CYP3A4 inhibitors."] |
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| Fetal Monitoring | No specific maternal-fetal monitoring is mandated. However, due to the potential for immunomodulation, monitor pregnant women for signs of infection or hypersensitivity reactions. Standard prenatal care including fetal ultrasound as clinically indicated is recommended. |
| Fertility Effects | Animal studies have shown no adverse effects on male or female fertility at exposures up to 3 times the human AUC. In humans, effects on fertility have not been studied; based on animal data and mechanism, no significant impact on fertility is anticipated. |