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. |
| Molecular Weight | 144000 |
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 | No adequate human data; based on animal studies, may cause fetal harm. Avoid use during first trimester unless benefit outweighs risk. |
| 2nd trimester | Limited human data; no evidence of teratogenicity in second trimester, but unknown effects on fetal immune system. Use with caution. |
| 3rd trimester | Potential risk of hematologic abnormalities (e.g., anemia, thrombocytopenia) in neonate due to daclizumab's pharmacologic action. Weigh risks vs benefits. |
Clinical note
Comprehensive clinical and safety monograph for ZINBRYTA (ZINBRYTA).
| Placental transfer | Daclizumab is a humanized monoclonal antibody (IgG1) which is actively transported across the placenta, especially during the third trimester. Fetal exposure is expected to be high. |
| Breastfeeding | Unknown if daclizumab is excreted in human milk. Because of the potential for adverse reactions in nursing infants, breastfeeding is not recommended during treatment and for 4 months after last dose. |
■ 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 |
Hypersensitivity to daclizumab or any excipientsActive hepatic impairment including autoimmune hepatitisHistory of autoimmune hepatitis or other autoimmune condition affecting the liver
| 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. |
| Food/Dietary | No known food interactions. ZINBRYTA can be taken with or without food. |
Loading safety data…
| Lactation Rating | L5 (contraindicated) |
| 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. |
| 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. |
| Clinical Pearls | ZINBRYTA (daclizumab) is a humanized monoclonal antibody that binds to CD25 (alpha subunit of IL-2 receptor) and inhibits high-affinity IL-2 binding, reducing T-cell activation. It is indicated for relapsing forms of multiple sclerosis (MS). Due to its association with severe autoimmune reactions including hepatic injury, colitis, and skin reactions, it was withdrawn from the market globally in 2018. Monitor liver function tests monthly, and assess for signs of colitis, rash, and lymphadenopathy. Do not use in patients with pre-existing liver disease or autoimmune conditions. Contraindicated in patients with hypersensitivity to daclizumab or any excipients. |
| Patient Advice | ZINBRYTA is given as a subcutaneous injection once monthly. · Contact your healthcare provider immediately if you experience symptoms of liver injury such as yellowing of the skin or eyes, dark urine, nausea, vomiting, or right upper abdominal pain. · Watch for signs of colitis like persistent diarrhea, bloody stools, or abdominal cramping. · Report any skin rashes, new or worsening, as serious skin reactions may occur. · Do not receive live vaccines while on ZINBRYTA and discuss vaccination history with your doctor. · Tell your doctor if you have a history of hepatitis or other liver problems, or any autoimmune condition. · Pregnancy should be avoided; effective contraception is recommended during treatment and for 4 months after the last dose. · Store vials in the refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze or shake. · If a dose is missed, contact your healthcare provider for instructions; do not double the dose. · Carry a patient alert card at all times indicating you are receiving ZINBRYTA. |