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ALERT: U.S. Boxed Warning
The FDA-approved labeling includes a boxed warning. See Warnings/Precautions section for a concise summary of this information. For verbatim wording of the boxed warning, consult the product labeling or www.fda.gov.
Pronunciation
(dac KLYE zue mab)
Generic Available (U.S.)
No
Index Terms
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Prophylaxis of acute rejection in renal transplantation (in combination with cyclosporine and corticosteroids)
Use: Unlabeled/Investigational
Treatment of refractory acute graft-versus-host disease; prevention of cardiac transplant rejection
Pregnancy Risk Factor
C
Pregnancy Considerations
An increased risk of fetal loss was observed in animal reproduction studies. Generally, IgG molecules cross the placenta. Use during pregnancy only if the potential benefit to the mother outweighs the possible risk to the fetus. Women of childbearing potential should use effective contraception before, during, and for 4 months following daclizumab treatment.
Lactation
Excretion in breast milk unknown/not recommended
Contraindications
Hypersensitivity to daclizumab or any component of the formulation
Warnings/Precautions
Boxed warnings:
• Experienced physician: See “Other warnings/precautions” below.
Concerns related to adverse effects:
• Anaphylaxis/hypersensitivity reactions: Severe acute hypersensitivity reactions, including anaphylaxis, have been observed on initial exposure and following re-exposure; medications for the management of severe allergic reaction should be available for immediate use. Hypersensitivity reactions may include bronchospasm, cyanosis, hypoxia, laryngeal edema, pulmonary edema, respiratory arrest, wheezing, hypotension, peripheral edema, diaphoresis, fever, loss of consciousness, rash, pruritus, urticaria, and/or injection site reactions. Permanently discontinue for severe hypersensitivity reaction. The risks of subsequent treatment courses are unknown and should be undertaken with caution.
• Immunogenicity: Anti-idiotype antibodies have been measured in patients who have received daclizumab (adults 14%; children 34%); detection of antibodies may be influenced by multiple factors and may, therefore, be misleading.
• Infections: Patients on immunosuppressive therapy are at increased risk for infectious complications; long-term effects on immune function are unknown.
• Mortality: An immunosuppressive regimen in cardiac transplant recipients which included daclizumab, cyclosporine, mycophenolate, and corticosteroids is associated with an increased in mortality (related to an increased incidence of severe infections), when compared to cyclosporine, mycophenolate, and corticosteroids plus placebo; higher mortality is also associated with concomitant use of antilymphocyte globulin.
• Secondary malignancy: Patients on immunosuppressive therapy are at increased risk for secondary malignancies; long-term effects on immune function are unknown.
Other warnings/precautions:
• Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of a physician experienced in immunosuppressive therapy and organ transplant management.
Adverse Reactions
Adverse effects reported during clinical trial use of daclizumab may be related to the patient population, transplant procedure, and concurrent transplant medications; incidences reported with daclizumab were similar to those reported with placebo. Diarrhea, fever, postoperative pain, pruritus, respiratory tract infection, urinary tract infection, hypertension (aggravated), and vomiting occurred more often in children than adults.
≥5%:
Cardiovascular: Chest pain, edema (including peripheral), hyper-/hypotension, tachycardia, thrombosis
Central nervous system: Dizziness, fatigue, fever, headache, insomnia, pain, post-traumatic pain
Dermatologic: Acne, cellulitis, wound healing impaired
Endocrine & metabolic: Hyperglycemia (32%)
Gastrointestinal: Abdominal distention, abdominal pain, constipation, diarrhea, dyspepsia, epigastric pain, nausea, pyrosis, vomiting
Genitourinary: Dysuria
Hematologic: Bleeding
Neuromuscular & skeletal: Back pain, musculoskeletal pain, tremor
Renal: Oliguria, renal tubular necrosis
Respiratory: Cough, dyspnea, pulmonary edema
Miscellaneous: Anti-daclizumab antibody formation (children 34%; adults 14%), malignancy (2% to 6%), lymphocele, wound infection
≥2% to <5%:
Central nervous system: Anxiety, depression, shivering
Dermatologic: Hirsutism, pruritus, rash
Endocrine & metabolic: Dehydration, diabetes mellitus, fluid overload
Gastrointestinal: Flatulence, gastritis, hemorrhoids
Genitourinary: Urinary retention, urinary tract bleeding
Local: Injection site reaction
Neuromuscular & skeletal: Arthralgia, leg cramps, myalgia, neuropathy, weakness
Ocular: Vision blurred
Renal: Hydronephrosis, renal damage, renal insufficiency
Respiratory: Abnormal breath sounds, atelectasis, congestion, hypoxia, pharyngitis, pleural effusion, rales, rhinitis
Miscellaneous: Diaphoresis, night sweats
<1%, postmarketing, and/or case reports: Severe hypersensitivity reaction/anaphylaxis (including bronchospasm, cardiac arrest, cardiac arrhythmia, cyanosis, hypotension, laryngeal edema, loss of consciousness, pulmonary edema, pruritus, respiratory arrest, urticaria, and wheezing); cytokine release syndrome
Drug Interactions
BCG: Immunosuppressants may diminish the therapeutic effect of BCG. Risk X: Avoid combination
Denosumab: May enhance the adverse/toxic effect of Immunosuppressants. Specifically, the risk for serious infections may be increased. Risk C: Monitor therapy
Echinacea: May diminish the therapeutic effect of Immunosuppressants. Risk D: Consider therapy modification
Leflunomide: Immunosuppressants may enhance the adverse/toxic effect of Leflunomide. Specifically, the risk for hematologic toxicity such as pancytopenia, agranulocytosis, and/or thrombocytopenia may be increased. Management: Consider not using a leflunomide loading dose in patients receiving other immunosuppressants. Patients receiving both leflunomide and another immunosuppressant should be monitored for bone marrow suppression at least monthly. Risk D: Consider therapy modification
Natalizumab: Immunosuppressants may enhance the adverse/toxic effect of Natalizumab. Specifically, the risk of concurrent infection may be increased. Risk X: Avoid combination
Pimecrolimus: May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Roflumilast: May enhance the immunosuppressive effect of Immunosuppressants. Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants may diminish the therapeutic effect of Sipuleucel-T. Risk C: Monitor therapy
Tacrolimus (Topical): May enhance the adverse/toxic effect of Immunosuppressants. Risk X: Avoid combination
Trastuzumab: May enhance the neutropenic effect of Immunosuppressants. Risk C: Monitor therapy
Vaccines (Inactivated): Immunosuppressants may diminish the therapeutic effect of Vaccines (Inactivated). Risk C: Monitor therapy
Vaccines (Live): Immunosuppressants may enhance the adverse/toxic effect of Vaccines (Live). Vaccinial infections may develop. Immunosuppressants may diminish the therapeutic effect of Vaccines (Live). Management: Avoid use of live organism vaccines with immunosuppressants; live-attenuated vaccines should not be given for at least 3 months after immunosuppressants. Risk X: Avoid combination
Storage
Refrigerate intact vials at 2°C to 8°C (36°F to 46°F); do not freeze. Do not shake. Protect undiluted solution from direct light. Do not use if solution is discolored or particulate matter is present. Solutions diluted for infusion in 0.9% sodium chloride are stable for 24 hours at 4°C or for 4 hours at room temperature.
Reconstitution
Dilute in 50 mL 0.9% sodium chloride prior to administration; mix by gently inverting bag to avoid foaming; do not shake. Do not use if solution is discolored or particulate matter is present. Do not mix with other medications or infuse other medications through same I.V. line.
Compatibility
Do not mix with other medications or infuse other medications through same I.V. line.
Mechanism of Action
Daclizumab is a chimeric (90% human, 10% murine) monoclonal IgG antibody produced by recombinant DNA technology. Daclizumab inhibits immune reactions by binding and blocking the alpha-chain of the Tac subunit of the interleukin-2 receptor (CD25) complex located on the surface of activated lymphocytes.
Pharmacodynamics/Kinetics
Distribution: Vd:
Adults: Central compartment: 0.031 L/kg; Peripheral compartment: 0.043 L/kg
Children: Central compartment: 0.067 L/kg; Peripheral compartment: 0.047 L/kg
Half-life elimination (estimated): Adults: Terminal: ~20 days (range: 11-38 days); Children: ~13 days
Dosage
I.V.:
Children:
Prophylaxis of acute renal transplant rejection: 1 mg/kg within 24 hours before transplantation (day 0), then every 14 days for 4 additional doses (total of 5 doses). Note: Daclizumab is used adjunctively with other immunosuppressants (cyclosporine and corticosteroids).
Treatment of refractory acute graft-versus-host disease (unlabeled use): 1 mg/kg on days 1, 4, 8, 15, and 22 (Perales, 2007; Prezpiorka, 2000)
Adults:
Prophylaxis of acute renal transplant rejection: 1 mg/kg within 24 hours before transplantation (day 0), then every 14 days for 4 additional doses (total of 5 doses). Note: Daclizumab is used adjunctively with other immunosuppressants (cyclosporine and corticosteroids).
Prevention of cardiac transplant rejection (unlabeled use): 1 mg/kg (maximum dose: 100 mg); administer within 12 hours after heart transplant and on days 8, 22, 36, and 50 post-transplant (Hershberger, 2005)
Treatment of refractory acute graft-versus-host disease (unlabeled use): 1 mg/kg on days 1, 4, 8, 15, and 22 (Bordigoni, 2006; Srinivasan, 2004) or 1 mg/kg (maximum dose: 100 mg); on days 1, 4, 8, 15, and 22 (Prezpiorka, 2000)
Dosage adjustment in renal impairment: No adjustment needed.
Dosage adjustment in hepatic impairment: No data available for patients with severe impairment.
Administration: I.V.
For I.V. administration following dilution. Administer within 4 hours of preparation if stored at room temperature; infuse over a 15-minute period via a peripheral or central vein.
Monitoring Parameters
Serum glucose; monitor for signs and symptoms of hypersensitivity, infection, and development of malignancy
Patient Education
This medication, which may help to reduce transplant rejection, can only be administered by infusion. You will be monitored closely during infusion. Report immediately any respiratory or swallowing difficulty; tightness in jaw or throat; chest pain; or rash or pain at infusion site. You will be more susceptible to infection. Maintain adequate nutrition and hydration, unless instructed to restrict fluid intake. May cause elevated blood sugar, headache, dizziness, fatigue, back pain, leg cramps, musculoskeletal pain, nausea, or vomiting. Report chest pain or palpitations, persistent dizziness, respiratory difficulty, rash, infection (fever or chills), thirst, excessive urination, or weight loss.
Cardiovascular Considerations
An international, multicenter trial was published evaluating the use of daclizumab vs placebo with cyclosporine, mycophenolate, and corticosteroids in heart transplant recipients (Hershberger, 2005). The primary endpoint was a composite of moderate-severe cellular rejection, hemodynamically significant graft dysfunction, a second transplant, or death. At 6 months, a significantly smaller number of patients in the daclizumab group reached the endpoint when compared to the placebo group (36% vs 48%, p = 0.007). Although cytolytic therapy was excluded from the study, 40 patients in the daclizumab arm and 37 patients in the placebo arm received either muromonab-CB3, antithymocyte globulin, or antilymphocyte globulin. Cytolytic therapy was administered because of its renal-sparing properties or for acute rejection in most cases. Six patients in the daclizumab arm who received concurrent cytolytic therapy died from sepsis. No one in the placebo group who received cytolytic therapy died from sepsis. Daclizumab was efficacious as prophylaxis against acute cellular rejection after cardiac transplant. Concurrent or anticipated use of cytolytic therapy with daclizumab should be avoided.
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause depression, anxiety, or insomnia
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Assess cardiorespiratory and renal function (fluid overload) during infusion and periodically between infusions. May cause hyperglycemia. Be alert to the possibility of the development of infection. Malignancies may occur with long-term use. Hypersensitivity reactions can occur. Treatment for severe allergic reactions should be available for immediate use.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Injection, solution [concentrate, preservative free]:
Zenapax®: 5 mg/mL (5 mL [DSC]) [contains polysorbate 80]
References
Bordigoni P, Dimicoli S, Clement L, et al, “Daclizumab, an Efficient Treatment for Steroid-Refractory Acute Graft-Versus-Host Disease,” Br J Haematol, 2006, 135(3):382-5.
Hershberger RE, Starling RC, Eisen HJ, et al, "Daclizumab to Prevent Rejection After Cardiac Transplantation," N Engl J Med, 2005, 352(26):2705-13.
Perales MA, Ishill N, Lomazow WA, et al, “Long-Term Follow-Up of Patients Treated With Daclizumab for Steroid-Refractory Acute Graft-Versus-Host Disease,” Bone Marrow Transplant, 2007, 40(5):481-6.
Przepiorka D, Kernan NA, Ippoliti C, et al, “Daclizumab, a Humanized Anti-Interleukin-2 Receptor Alpha Chain Antibody, for Treatment of Acute Graft-Versus-Host Disease,” Blood, 2000, 95(1):83-9.
Srinivasan R, Chakrabarti S, Walsh T, et al, “Improved Survival in Steroid-Refractory Acute Graft Versus Host Disease After Non-Myeloablative Allogeneic Transplantation Using a Daclizumab-Based Strategy With Comprehensive Infection Prophylaxis,” Br J Haematol, 2004, 124(6):777-86.
Vincenti F, Kirkman R, Light S, et al, “Interleukin-2-Receptor Blockade With Daclizumab to Prevent Acute Rejection in Renal Transplantation. Daclizumab Triple Therapy Study Group,” N Engl J Med, 1998, 338(3):161-5.
Wiseman LR and Faulds D, "Daclizumab: A Review of Its Use in the Prevention of Acute Rejection in Renal Transplant Recipients," Drugs, 1999, 58(6):1029-42.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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