MACUGEN
Clinical safety rating: caution
Comprehensive clinical and safety monograph for MACUGEN (MACUGEN).
Pegaptanib is a pegylated modified oligonucleotide that binds to and inhibits vascular endothelial growth factor (VEGF-165), reducing angiogenesis and vascular permeability.
| Metabolism | Pegaptanib is metabolized by endonucleases and exonucleases; not metabolized by CYP450 enzymes. |
| Excretion | Pegaptanib is eliminated primarily via renal excretion, with the parent compound and metabolites excreted in urine accounting for >90% of the administered dose. Biliary/fecal elimination is negligible (<5%). |
| Half-life | The terminal elimination half-life in plasma is approximately 10 days following intravitreal administration, consistent with slow clearance from the vitreous cavity and systemic absorption. |
| Protein binding | Protein binding is approximately 94% in human plasma, primarily to albumin and other plasma proteins. |
| Volume of Distribution | Volume of distribution is approximately 0.04 L/kg, indicating limited extravascular distribution and confinement primarily to the vascular space. |
| Bioavailability | Bioavailability is essentially 100% following intravitreal injection. Systemic bioavailability after intravitreal administration is low (approximately 0.1% of the injected dose). |
| Onset of Action | Onset of action occurs within 2 weeks after a single intravitreal injection, with maximal reductions in vascular leakage observed at 4–6 weeks. |
| Duration of Action | Duration of action after a single 0.3 mg intravitreal injection is approximately 6 weeks, supporting the recommended dosing interval of every 6 weeks. |
Intravitreal injection of 0.3 mg (0.09 mL) once every 6 weeks.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for renal impairment; data limited for GFR <15 mL/min/1.73 m². |
| Liver impairment | No dose adjustment required for hepatic impairment; not studied in severe impairment (Child-Pugh C). |
| Pediatric use | Safety and efficacy not established in pediatric patients; no recommended dose. |
| Geriatric use | No specific dose adjustment; pharmacokinetics not significantly altered by age; monitor for ocular adverse events. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for MACUGEN (MACUGEN).
| Breastfeeding | It is unknown whether pegaptanib is excreted in human breast milk. Due to the very low systemic absorption following intravitreal injection, the M/P (milk-to-plasma) ratio is expected to be negligible. However, caution should be exercised as a risk cannot be excluded. The American Academy of Pediatrics considers compatible with breastfeeding if administered in standard ophthalmic doses. |
| Teratogenic Risk | Pegaptanib (Macugen) is an anti-VEGF agent administered via intravitreal injection. There are no adequate and well-controlled studies in pregnant women. Systemic exposure is negligible due to intravitreal administration, but theoretical risk exists for fetal harm if systemic absorption occurs. In animal studies, no teratogenic effects were observed at doses much higher than human exposure. First trimester use carries unknown risk; second and third trimester use considered low risk due to minimal systemic absorption. |
■ FDA Black Box Warning
WARNING: INTRAOCULAR INJECTION-RELATED ENDOPHTHALMITIS. There have been reports of endophthalmitis following intravitreal injection. Proper aseptic technique must be used.
| Serious Effects |
["Ocular or periocular infection","Active intraocular inflammation"]
| Precautions | ["Endophthalmitis: Strict aseptic technique required.","Increased intraocular pressure (IOP): Monitor IOP post-injection.","Anaphylaxis/anaphylactoid reactions: Immediately discontinue if signs occur.","Thromboembolic events: Possible increased risk in patients with prior stroke or TIA."] |
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| Fetal Monitoring | No specific maternal or fetal monitoring is required beyond standard ophthalmic care. Monitor for any signs of systemic adverse effects (e.g., hypertension, proteinuria) which are rare. Fetal monitoring only indicated if maternal systemic toxicity occurs, which is unlikely given local administration. |
| Fertility Effects | No studies on fertility have been conducted in humans. In animal studies, no impairment of fertility was observed at doses up to 500 times the human intravitreal dose. Based on the local route and minimal systemic absorption, no significant effects on fertility are expected. |