ZYMFENTRA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZYMFENTRA (ZYMFENTRA).
Tumor necrosis factor (TNF) alpha inhibitor; biosimilar to infliximab. Binds to soluble and membrane-bound TNF-alpha, preventing interaction with p55 and p75 TNF receptors, reducing inflammatory signaling.
| Metabolism | Primarily metabolized by nonspecific proteolysis; not metabolized by cytochrome P450 enzymes. |
| Excretion | ZYMFENTRA (infliximab) is eliminated primarily via the reticuloendothelial system and target-mediated clearance. Fecal excretion accounts for less than 10% of the administered dose. Renal excretion is minimal (<0.1%) as intact immunoglobulin. Biliary excretion is negligible. The majority of clearance occurs through cellular internalization and catabolism. |
| Half-life | Terminal elimination half-life is approximately 7.7 to 9.5 days. Clinical context: This supports a dosing interval of every 8 weeks for maintenance therapy in most indications. Patients with positive anti-drug antibodies may have accelerated clearance and reduced half-life. |
| Protein binding | Infliximab binds to TNF-alpha with high affinity; its protein binding to plasma proteins is minimal. Approximately 10% of the dose is bound to plasma proteins, primarily to immunoglobulins and albumin. The vast majority circulates as free monoclonal antibody. |
| Volume of Distribution | Volume of distribution at steady state (Vd) ranges from 3 to 6 L, approximately 0.04 to 0.08 L/kg for a 70 kg adult. This reflects distribution primarily within the vascular space and limited extravascular penetration, consistent with a large monoclonal antibody. |
| Bioavailability | Subcutaneous administration: Absolute bioavailability is approximately 58% (range 43-74%) compared to intravenous infliximab. Subcutaneous administration achieves peak concentrations at 2-3 days post-dose and provides sustained exposure over the dosing interval. |
| Onset of Action | Subcutaneous administration: Clinical response (e.g., reduction in fistula drainage, improvement in Crohn's Disease Activity Index) may be observed within 2 weeks. Intravenous administration is not applicable as ZYMFENTRA is only available as subcutaneous injection. |
| Duration of Action | Duration of therapeutic effect is 8 weeks for maintenance therapy. Clinical notes: Some patients may require dose escalation or shortened intervals due to loss of response. Sustained remission may be achieved with regular dosing. |
120 mg subcutaneously every 2 weeks after a 40 mg intravenous loading dose at week 0.
| Dosage form | INJECTABLE |
| Renal impairment | No dosage adjustment required for mild to moderate renal impairment (GFR ≥30 mL/min); safety and efficacy not established in severe renal impairment (GFR <30 mL/min). |
| Liver impairment | No dosage adjustment required for mild hepatic impairment (Child-Pugh A); not recommended in moderate to severe hepatic impairment (Child-Pugh B or C). |
| Pediatric use | Not approved for pediatric use; safety and efficacy not established in patients <18 years of age. |
| Geriatric use | No specific dose adjustment recommended; monitor for infections and adverse reactions due to greater frequency of decreased hepatic, renal, or cardiac function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZYMFENTRA (ZYMFENTRA).
| Breastfeeding | Infliximab is excreted in human milk in low amounts. The milk-to-plasma ratio is approximately 0.02-0.04. Degradation in the infant gastrointestinal tract limits systemic absorption. Considered compatible with breastfeeding, but caution is advised if the infant is immunocompromised. |
| Teratogenic Risk | ZYMFENTRA (infliximab) is a monoclonal antibody. IgG antibodies cross the placenta, with increasing transfer in the second and third trimesters. First trimester exposure: limited data suggest no major increase in congenital malformations. Second and third trimester exposure: may lead to detectable serum levels in the infant, potentially increasing risk of infections and altered immune response. Live vaccines should be avoided in infants exposed in utero for at least 6 months after birth. |
■ FDA Black Box Warning
Serious infections including tuberculosis, invasive fungal infections, and other opportunistic infections; increased risk of lymphoma and other malignancies, particularly hepatosplenic T-cell lymphoma in adolescents and young adults with inflammatory bowel disease.
| Serious Effects |
Hypersensitivity to infliximab or any murine proteins; moderate to severe heart failure (NYHA class III/IV).
| Precautions | Hepatotoxicity (including acute liver failure), hepatitis B reactivation, hypersensitivity reactions, hematologic cytopenias, demyelinating disease, heart failure exacerbation, lupus-like syndrome, and risk of infection. |
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| Fetal Monitoring | Monitor for maternal infections, infusion reactions, and disease activity. In the fetus/infant: watch for evidence of immunosuppression, infections, and timely vaccination schedule. Consider checking infant serum infliximab levels if concern for prolonged exposure. |
| Fertility Effects | No evidence of impaired fertility in animal studies. However, uncontrolled active inflammatory bowel disease may affect fertility. Use of ZYMFENTRA should not preclude pregnancy planning when disease is well-controlled. |