ZINBRYTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZINBRYTA (ZINBRYTA).
Daclizumab is a humanized monoclonal antibody that binds to the alpha subunit (CD25) of the high-affinity interleukin-2 (IL-2) receptor on activated T cells. By blocking IL-2 binding, it inhibits IL-2-mediated activation and proliferation of lymphocytes, which are involved in the pathogenesis of multiple sclerosis.
| Metabolism | Daclizumab is a monoclonal antibody; metabolic pathways are not fully characterized but likely involve catabolic degradation via general protein catabolism. |
| Excretion | Excreted primarily via proteolytic catabolism; not renally or hepatically eliminated. No specific biliary/fecal data available. |
| Half-life | Terminal half-life approximately 21 days (range 18-27 days) following subcutaneous administration, supporting monthly dosing interval. |
| Protein binding | No specific protein binding data; as a monoclonal antibody, likely low nonspecific binding to plasma proteins. |
| Volume of Distribution | Volume of distribution approximately 8.2 L (0.12 L/kg for a 70 kg adult), reflecting limited extravascular distribution. |
| Bioavailability | Subcutaneous: Bioavailability approximately 93% after abdominal injection; intravenous administration not approved. |
| Onset of Action | Subcutaneous: Clinical effect (reduction in annualized relapse rate) observed within 4 weeks; maximal effect by 12-16 weeks. |
| Duration of Action | Duration of pharmacological effect sustained for at least 4 weeks post-dose; clinical benefit persists with continued monthly dosing. |
150 mg subcutaneously once weekly
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for renal impairment. Not studied in patients with severe renal impairment (eGFR <15 mL/min/1.73 m2) or on dialysis. |
| 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 patients under 18 years of age. |
| Geriatric use | No specific dose adjustment recommended based on age. Clinical studies included patients up to 60 years, with limited data in those over 60. Use with caution due to potential increased risk of adverse effects. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZINBRYTA (ZINBRYTA).
| Breastfeeding | It is unknown whether daclizumab is excreted in human milk. However, because immunoglobulins are secreted into breast milk, and due to the potential for serious adverse reactions (e.g., hepatotoxicity, infections) in nursing infants, women should not breastfeed during treatment and for at least 4 months after the last dose. No M/P ratio is available. |
| Teratogenic Risk | ZINBRYTA (daclizumab) is contraindicated in pregnancy. Based on its mechanism of action (IL-2 receptor blockade) and animal studies, there is a potential for fetal harm. Monoclonal antibodies are known to cross the placenta increasingly after the first trimester. Use during the second and third trimesters may be associated with immunosuppression and increased risk of infection in the neonate. There are no adequate human data; however, due to the high risk of hepatotoxicity and other adverse effects, pregnancy should be avoided. |
■ FDA Black Box Warning
WARNING: HEPATIC INJURY AND IMMUNE-MEDIATED DISORDERS. ZINBRYTA can cause severe liver injury, including hepatocellular injury, jaundice, and hepatic failure, which can be life-threatening or fatal. It also increases the risk of immune-mediated disorders, including colitis, lymphadenopathy, and non-infectious meningitis.
| Serious Effects |
["History of severe hypersensitivity reaction to daclizumab or any component of the formulation.","Pre-existing liver disease or hepatic impairment (e.g., ALT/AST >2x ULN or bilirubin >1.5x ULN).","Active infection or history of autoimmune disorders (relative)."]
| Precautions | ["Hepatic injury: monitor liver enzymes and bilirubin before and during treatment.","Immune-mediated disorders: monitor for signs of colitis, lymphadenopathy, and meningitis.","Hypersensitivity reactions, including anaphylaxis.","Infections: avoid use in patients with active infection.","Immunizations: avoid live vaccines during treatment."] |
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| Fetal Monitoring | If ZINBRYTA is used inadvertently during pregnancy, close monitoring of maternal liver function (due to risk of autoimmune hepatitis) and fetal growth/development via ultrasound is recommended. Neonates should be monitored for immunosuppression (e.g., infections, abnormal immune function) and hepatotoxicity. |
| Fertility Effects | No human studies have evaluated effects on fertility. In animal studies, daclizumab had no adverse effects on male or female fertility at doses up to 100 mg/kg. However, due to its immunomodulatory effects, theoretical risk of impact on reproductive function cannot be excluded. |