ENZEEVU
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ENZEEVU (ENZEEVU).
Enzeevu (aflibercept) is a vascular endothelial growth factor (VEGF) inhibitor. It acts as a soluble decoy receptor that binds to VEGF-A, VEGF-B, and placental growth factor (PlGF), thereby preventing their interaction with cell surface receptors (VEGFR1 and VEGFR2), reducing angiogenesis and vascular permeability.
| Metabolism | Aflibercept is a protein; metabolism is via proteolytic degradation into smaller peptides and amino acids. No cytochrome P450 involvement. |
| Excretion | Primarily renal excretion as unchanged drug (approximately 70%) and fecal excretion (approximately 20%) after intravenous administration. Biliary excretion is minor (<10%). |
| Half-life | Terminal elimination half-life is approximately 12 hours (range 10-14 hours) in healthy adults. This supports once-daily dosing. Half-life may be prolonged in patients with renal impairment. |
| Protein binding | Approximately 94% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is approximately 0.3 L/kg, indicating distribution primarily in extracellular fluid and plasma. |
| Bioavailability | Intravenous: 100%. Subcutaneous: Absolute bioavailability is 65% after abdominal subcutaneous administration. |
| Onset of Action | Intravenous: Clinical effect (anticoagulation) is observed within 2 to 4 hours after start of infusion. Subcutaneous: Onset is approximately 3 to 5 hours after administration. |
| Duration of Action | Anticoagulant effect persists for approximately 12 to 24 hours after a single dose, consistent with the half-life. Once-daily dosing maintains continuous anticoagulation. |
200 mg subcutaneously every 4 weeks
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for any degree of renal impairment |
| Liver impairment | No dose adjustment required for any degree of hepatic impairment (including Child-Pugh C) |
| Pediatric use | Not approved for use in pediatric patients |
| Geriatric use | No specific dose adjustment required; use standard adult dosing |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ENZEEVU (ENZEEVU).
| Breastfeeding | No human data on presence in breast milk. Enzalutamide is highly protein-bound (>97%) and has a large volume of distribution; M/P ratio is unknown. Due to potential for serious adverse reactions (e.g., fetal harm in exposed infants), breastfeeding is not recommended during treatment and for at least 1 month after last dose. |
| Teratogenic Risk | Pregnancy Category D. Enzaluamide (ENZEEVU) is associated with fetal harm based on its mechanism of action (androgen receptor inhibition). In animal studies, maternal exposure resulted in dose-dependent fetal anomalies, including skeletal abnormalities and reduced fetal growth. Use is contraindicated in pregnant women. If exposure occurs during pregnancy, inform patient of potential risks; first trimester exposure carries highest risk for major malformations. |
■ FDA Black Box Warning
No black box warning.
| Serious Effects |
Ocular or periocular infections, active intraocular inflammation, hypersensitivity to aflibercept or any excipients.
| Precautions | ["Endophthalmitis and retinal detachment (intravitreal injection procedure-related)","Increase in intraocular pressure (transient or sustained)","Thromboembolic events (arterial thromboembolic events, including stroke and myocardial infarction, have been reported rarely)"] |
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| Fetal Monitoring | For women of reproductive potential, confirm negative pregnancy test before initiating therapy. Monitor for signs of fetal distress if inadvertent exposure occurs; no specific fetal monitoring guidelines exist. In animal studies, reduced fetal weight and skeletal variations were observed; consider ultrasound for fetal growth and anatomy if exposure happens. |
| Fertility Effects | Enzalutamide impairs spermatogenesis and reduces fertility in males based on animal studies. Effects on female fertility are not well-studied; it may disrupt menstrual cycles due to androgen receptor blockade. Reversibility is unknown. Advise men with partners of reproductive potential to use effective contraception during and for 3 months after treatment. |