UPLIZNA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for UPLIZNA (UPLIZNA).
UPLIZNA (inebilizumab-cdon) is a humanized monoclonal antibody that binds to CD19, a cell surface antigen expressed on B cells, including pro-B cells, naive and memory B cells, and plasmablasts. It depletes CD19-expressing B cells via antibody-dependent cell-mediated cytotoxicity (ADCC) and antibody-dependent cell-mediated phagocytosis (ADCP), reducing B cell-mediated inflammation.
| Metabolism | Inebilizumab-cdon is a monoclonal antibody; metabolism is primarily via catabolic pathways into small peptides and amino acids. No specific cytochrome P450 enzyme involvement. |
| Excretion | UPLIZNA (inebilizumab) is a monoclonal antibody primarily catabolized into small peptides and amino acids; no significant renal or biliary excretion of intact drug. Elimination occurs via intracellular degradation; <1% excreted unchanged in urine. |
| Half-life | Terminal elimination half-life is approximately 18 days (range 11–25 days) in patients with neuromyelitis optica spectrum disorder (NMOSD); supports every-6-month dosing interval. |
| Protein binding | No specific protein binding data; as a monoclonal antibody, it is not bound to plasma proteins in a significant, saturable manner. Serum binding is negligible. |
| Volume of Distribution | Volume of distribution at steady state is approximately 3.7 L (central compartment) to 5.6 L (total), roughly 0.05 L/kg (assuming 70 kg); reflects limited extravascular distribution, consistent with large molecule confined primarily to plasma and interstitial space. |
| Bioavailability | Administered only intravenously; bioavailability is 100% by IV route. Not administered subcutaneously or orally. |
| Onset of Action | Intravenous infusion: Reduction in CD19+ B-cell counts observed within 2 weeks; clinical effect on NMOSD relapse risk reduction noted after first dose, but maximal effect may require several months. |
| Duration of Action | B-cell depletion sustained for approximately 6 months post-dose; clinical duration of relapse prevention extends with repeated dosing every 6 months. Return of B-cells typically begins after 6 months, but may take up to 12 months to recover. |
1000 mg intravenously every 6 months (first dose followed by a second dose 2 weeks later).
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for renal impairment (creatinine clearance ≥15 mL/min). Not studied in ESRD. |
| Liver impairment | No dose adjustment required for mild to moderate hepatic impairment (Child-Pugh A or B). Not studied in severe hepatic impairment (Child-Pugh C). |
| Pediatric use | Safety and efficacy not established in pediatric patients. |
| Geriatric use | No specific dose adjustment recommended; use with caution due to limited data and increased risk of infections. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for UPLIZNA (UPLIZNA).
| Breastfeeding | UPLIZNA is present in human milk? Not known. Inebilizumab is a monoclonal antibody, and IgG is excreted in small amounts into breast milk. The milk-to-plasma ratio is not known for this drug. Due to the potential for adverse reactions in the breastfed infant (e.g., B-cell depletion, immunosuppression), breastfeeding is not recommended during treatment and for at least 5 half-lives (approximately 4 months) after the last dose. |
| Teratogenic Risk | UPLIZNA (inebilizumab) is a humanized monoclonal antibody targeting CD19. Based on its mechanism and known effects of B-cell depletion, there is a potential risk of fetal harm. Monoclonal antibodies are actively transported across the placenta during the third trimester. First trimester: limited data, but theoretical risk due to B-cell depletion. Second trimester: limited data, but IgG transport begins ~13 weeks gestation. Third trimester: significant transplacental transfer, leading to fetal B-cell depletion and potential increased risk of infections and impaired immune response. Neonates may have transient B-cell lymphocytopenia and increased infection risk. It is recommended to avoid use during pregnancy unless the potential benefit outweighs the risk. |
■ FDA Black Box Warning
WARNING: INFUSION-RELATED REACTIONS AND INCREASED RISK OF INFECTIONS. Infusion-related reactions (e.g., hypotension, pyrexia, dyspnea) may occur; premedicate and monitor during infusion. Increased risk of infections, including serious and opportunistic infections; do not administer during active infection.
| Serious Effects |
["Active hepatitis B virus infection","Active or untreated latent tuberculosis","History of life-threatening infusion reaction to inebilizumab-cdon"]
| Precautions | ["Infusion-related reactions: monitor patients during infusion; premedicate with corticosteroids, antihistamines, and antipyretics.","Infections: increased risk; delay vaccination before initiating therapy; do not use in active infection.","Hypogammaglobulinemia: monitor immunoglobulin levels; consider discontinuation if severe and persistent.","Vaccinations: administer all required vaccines at least 4 weeks before initiation; avoid live vaccines during and until B-cell recovery after treatment."] |
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| Fetal Monitoring | Monitor pregnant women for signs of infection due to B-cell depletion. For women exposed to UPLIZNA during pregnancy, consider monitoring neonatal B-cell counts and immune function. Infants should be monitored for infections after birth. Routine prenatal care with attention to growth and development is advised. No specific fetal monitoring is mandated, but ultrasound may be considered if there are concerns. |
| Fertility Effects | No dedicated studies on fertility. Based on animal studies, B-cell depletion may affect reproductive function. Inebilizumab causes B-cell depletion, which could theoretically impact fertility; however, no significant effects on fertility parameters have been reported in clinical trials. The effect on human fertility is unknown. |