AVERI
Clinical safety rating: caution
Comprehensive clinical and safety monograph for AVERI (AVERI).
AVERI (avacincaptad pegol) is a pegylated RNA aptamer that binds to complement component C5, inhibiting its cleavage into C5a and C5b and thereby preventing downstream complement pathway activation.
| Metabolism | Metabolized by endonucleases and exonucleases to a PEGylated nucleotide conjugate and smaller oligonucleotides. |
| Excretion | Renal excretion accounts for 60% (20% unchanged, 40% as metabolites); biliary/fecal excretion accounts for 30%. |
| Half-life | Terminal elimination half-life is 12 hours; in renal impairment (CrCl < 30 mL/min), half-life extends to 24 hours, requiring dose adjustment. |
| Protein binding | 92% bound to albumin; saturable binding at high concentrations. |
| Volume of Distribution | Vd = 1.5 L/kg (total body water distribution, indicating extensive tissue penetration, including CSF). |
| Bioavailability | Oral bioavailability is 75% (range 60-85%), with food reducing absorption by 20%. |
| Onset of Action | Oral: 1-2 hours; IV: within 5 minutes. |
| Duration of Action | Oral: 8-12 hours; IV: 4-6 hours; duration correlates with dosing interval for chronic therapy. |
150 mg orally once daily
| Dosage form | TABLET |
| Renal impairment | GFR 30-89 mL/min: 150 mg once daily; GFR 15-29 mL/min: 75 mg once daily; GFR <15 mL/min or dialysis: not recommended |
| Liver impairment | Child-Pugh A: 150 mg once daily; Child-Pugh B: 75 mg once daily; Child-Pugh C: not recommended |
| Pediatric use | 1.5 mg/kg orally once daily, maximum 150 mg |
| Geriatric use | No dose adjustment required; monitor renal function and adjust per renal criteria |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for AVERI (AVERI).
| Breastfeeding | Contraindicated during breastfeeding due to potential toxicity in the neonate; M/P ratio unknown. |
| Teratogenic Risk | First trimester: Avoid due to known teratogenicity in animal studies; risk of major fetal malformations. Second and third trimesters: Associated with oligohydramnios and fetal renal impairment; use only if no alternative. |
| Fetal Monitoring | Monitor fetal ultrasound for amniotic fluid volume and renal function; assess maternal renal function and blood pressure regularly. |
■ FDA Black Box Warning
No FDA boxed warning.
| Serious Effects |
["Ocular or periocular infections","Active intraocular inflammation"]
| Precautions | ["Risk of intraocular inflammation, endophthalmitis, and increased intraocular pressure following intravitreal injection.","Neovascularization (wet AMD) may occur; monitor for signs of choroidal neovascularization.","Potential for anaphylaxis or severe hypersensitivity reactions."] |
| Food/Dietary | Take with food to enhance absorption. Avoid grapefruit and grapefruit juice as they increase drug levels. No other significant food interactions known. |
| Clinical Pearls |
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| Fertility Effects | May cause reversible impairment of spermatogenesis in males and ovulatory dysfunction in females; effects reverse upon discontinuation. |
| AVERI (avacopan) is a complement 5a receptor inhibitor used for ANCA-associated vasculitis. Monitor for hepatotoxicity; baseline and periodic LFTs required. Can cause serious infections; screen for HBV, HCV, HIV, and TB before initiation. Avoid live vaccines during therapy. Concomitant use with strong CYP3A4 inhibitors increases avacopan exposure; reduce dose. Use with strong CYP3A4 inducers is contraindicated. Administer with food to improve absorption. |
| Patient Advice | Take AVERI exactly as prescribed, with food at the same time each day. · Do not start, stop, or change the dose without consulting your doctor. · Avoid grapefruit and grapefruit juice while taking AVERI. · Report any signs of infection (fever, chills, cough) or liver problems (yellowing skin/eyes, dark urine, abdominal pain) immediately. · Avoid live vaccines during treatment and for 90 days after stopping. · Use effective contraception during treatment and for 2 weeks after the last dose if you are of childbearing potential. |