IZERVAY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for IZERVAY (IZERVAY).
IZERVAY (avacincaftad pegol) is a complement C5 inhibitor that binds to complement protein C5, preventing its cleavage into C5a and C5b and thereby inhibiting the formation of the membrane attack complex (MAC) and reducing complement-mediated inflammation and cell damage.
| Metabolism | Metabolized by catabolism via general protein degradation pathways; not significantly metabolized by CYP450 enzymes. |
| Excretion | IZERVAY (avacincaptad pegol) is eliminated primarily via renal excretion as unchanged drug. Renal clearance accounts for approximately 90% of total clearance, with <10% excreted in feces. |
| Half-life | The terminal elimination half-life is approximately 14 days (range 11–18 days) based on intravitreal administration, supporting monthly dosing intervals for sustained efficacy. |
| Protein binding | Avacincaptad pegol is approximately 65% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Volume of distribution is approximately 0.1 L/kg following intravitreal administration, indicating limited distribution outside the vitreous cavity and systemic circulation. |
| Bioavailability | Intravitreal: 100% (direct injection into the vitreous humor). Not administered via other routes. |
| Onset of Action | Intravitreal: Clinical effect (reduction in geographic atrophy lesion growth) observed as early as 6 months, with maximal effect by 12 months per phase 3 trials. |
| Duration of Action | Duration of action is approximately 1 month after intravitreal injection, consistent with the dosing interval of every 4 weeks (monthly) for the treatment of geographic atrophy secondary to age-related macular degeneration. |
15 mg/0.1 mL (150 mg/mL) intravitreal injection every 8-12 weeks for 2 years.
| Dosage form | SOLUTION |
| Renal impairment | No dose adjustment required for any degree of renal impairment. |
| Liver impairment | No dose adjustment required for Child-Pugh Class A, B, or C. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment; similar efficacy and safety as in younger adults based on clinical trials. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for IZERVAY (IZERVAY).
| Breastfeeding | Systemic absorption following intravitreal administration is minimal, and excretion into human breast milk is unlikely. No data on M/P ratio available. Caution is advised due to lack of data; consider developmental benefits of breastfeeding and clinical need for IZERVAY. |
| Teratogenic Risk | IZERVAY (avacincaptad pegol) is an intravitreal injection indicated for geographic atrophy secondary to age-related macular degeneration. Systemic absorption is negligible. No teratogenic effects are expected due to minimal systemic exposure. However, no adequate and well-controlled studies in pregnant women exist; animal reproductive studies have not been conducted. As a precaution, avoid use during pregnancy unless potential benefit justifies risk. |
■ FDA Black Box Warning
None
| Common Effects | Application site reactions burning irritation itching and redness |
| Serious Effects |
["Active ocular or periocular infections","Known hypersensitivity to avacincaftad pegol or any excipients in IZERVAY"]
| Precautions | ["Risk of endophthalmitis and retinal detachment with intravitreal injection","Increase in intraocular pressure within 30 minutes of injection","Potential for hypersensitivity reactions","Not recommended for use in patients with active ocular or periocular infections","Caution in patients with history of retinal detachment or macular hole"] |
| Food/Dietary | No significant food-drug interactions identified. No dietary restrictions are required. |
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| Fetal Monitoring | Routine monitoring for intraocular inflammation and increased intraocular pressure post-injection; no specific maternal or fetal monitoring required due to negligible systemic absorption. |
| Fertility Effects | No animal fertility studies have been conducted. Based on mechanism (anti-complement C5) and negligible systemic exposure, no significant impact on human fertility is expected. |
| Clinical Pearls | IZERVAY (avacincaptad pegol) is a complement C5 inhibitor administered via intravitreal injection for geographic atrophy (GA) secondary to age-related macular degeneration. Pre-injection antisepsis with povidone-iodine and topical antibiotic prophylaxis (e.g., moxifloxacin) are recommended to reduce endophthalmitis risk. Monitor for intraocular pressure elevation immediately post-injection; ensure sterile technique and use a 30-gauge needle. Efficacy is modest in slowing GA lesion growth; patients should have realistic expectations. Contraindicated in active ocular or periocular infections. |
| Patient Advice | IZERVAY is injected into the eye and requires multiple treatments every 4–6 weeks. · Common side effects include eye redness, discomfort, and floaters; call your doctor immediately if you experience severe pain, vision loss, or sensitivity to light. · Do not rub your eye after the injection to prevent infection or bleeding. · Avoid swimming, hot tubs, or dusty environments for at least 1 week after injection. · Report any symptoms of infection (e.g., discharge, swelling) or new floaters/flashes immediately. |