PORTRAZZA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PORTRAZZA (PORTRAZZA).
PORTRAZZA (necitumumab) is a recombinant human IgG1 monoclonal antibody that binds to the epidermal growth factor receptor (EGFR), thereby inhibiting ligand binding and subsequent activation of EGFR, leading to inhibition of downstream signaling pathways involved in cell proliferation and survival.
| Metabolism | Metabolism of necitumumab has not been fully characterized. As a monoclonal antibody, it is expected to be degraded into small peptides and amino acids via general protein catabolic pathways. |
| Excretion | Necitumumab is an IgG1 monoclonal antibody; elimination occurs via intracellular catabolism, with no significant renal or biliary excretion. No specific percentage of elimination via renal or fecal routes is established. |
| Half-life | Terminal elimination half-life is approximately 14 days (range 10–18 days). This long half-life supports dosing every 3 weeks and allows sustained receptor blockade. |
| Protein binding | Necitumumab is a monoclonal antibody; target-mediated binding to EGFR occurs, but nonspecific plasma protein binding is negligible. No specific protein binding percentage is reported. |
| Volume of Distribution | Volume of distribution at steady state is approximately 5.8 L (range 4.7–7.1 L), suggesting distribution primarily in the vascular space and minimal extravascular distribution. |
| Bioavailability | Intravenous: 100% (not applicable to other routes). |
| Onset of Action | Intravenous: Clinical effect (e.g., EGFR inhibition) occurs within hours of first dose; however, objective tumor response may take weeks to months. |
| Duration of Action | Duration of EGFR blockade persists for approximately 2–3 weeks after a single dose, aligning with the dosing interval. Clinical duration of effect is continuous with regular dosing. |
PORTRAZZA (necitumumab) is administered intravenously at a dose of 800 mg over 60 minutes on days 1 and 8 of each 21-day cycle.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment is recommended for patients with mild to moderate renal impairment. There is no data for severe renal impairment (CrCL <30 mL/min) or end-stage renal disease. |
| Liver impairment | No formal studies have been conducted in patients with hepatic impairment. No dose adjustment is recommended for mild hepatic impairment (Child-Pugh A). Use caution in moderate to severe hepatic impairment due to lack of data. |
| Pediatric use | Safety and effectiveness in pediatric patients have not been established. |
| Geriatric use | No specific dose adjustment is recommended for elderly patients. Clinical studies included patients aged 65 years and older; no overall differences in safety or efficacy were observed compared to younger patients. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PORTRAZZA (PORTRAZZA).
| Breastfeeding | It is not known whether necitumumab is excreted in human milk. Human IgG is known to be present in milk, but the amount is generally low. Due to the potential for serious adverse reactions in nursing infants, advise women not to breast-feed during treatment and for at least 3 months after the last dose. M/P ratio is unknown. |
| Teratogenic Risk | Portrazza (necitumumab) is an IgG1 monoclonal antibody. IgG molecules are actively transported across the placenta during the third trimester, potentially exposing the fetus to therapeutic concentrations. There are no adequate and well-controlled studies in pregnant women. Based on its mechanism of action (EGFR inhibition), there is a risk of fetal harm, including developmental abnormalities and fetal loss. Women of reproductive potential should use effective contraception during treatment and for at least 3 months after the last dose. |
■ FDA Black Box Warning
No black box warnings.
| Serious Effects |
["No known contraindications from the manufacturer."]
| Precautions | ["Cardiopulmonary arrest and/or sudden death occurred in 3% of patients receiving necitumumab in combination with gemcitabine and cisplatin; monitor electrolytes and consider withholding for severe electrolyte abnormalities.","Arterial thromboembolic events (ATEs) occurred in 5% of patients; permanently discontinue for serious ATEs.","Venous thromboembolic events (VTEs) including pulmonary embolism occurred; permanently discontinue for life-threatening VTEs.","Hemolytic-uremic syndrome (HUS) reported; discontinue if HUS is suspected.","Dermatologic toxicities including rash, dry skin, and pruritus; monitor and manage accordingly.","Infusion-related reactions; interrupt or discontinue for severe reactions.","Hypomagnesemia occurred in 83% of patients; monitor magnesium, calcium, and potassium prior to each dose.","Embryofetal toxicity: can cause fetal harm; advise females of reproductive potential of effective contraception."] |
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| Fetal Monitoring | Monitor for infusion-related reactions, electrolyte abnormalities (especially hypomagnesemia, hypocalcemia, hypokalemia), and thromboembolic events. In pregnant patients, consider fetal monitoring with ultrasound to assess for growth abnormalities and oligohydramnios, as EGFR inhibition may affect fetal development. |
| Fertility Effects | No formal fertility studies have been conducted with necitumumab. Based on its mechanism (EGFR inhibition), there is a potential for impairment of female fertility due to effects on follicular development and ovulation. Male fertility may also be affected based on animal studies with EGFR inhibitors showing testicular degeneration. |