Drugs Details

Drugs Info of Zenapax
Drugs Details
  • Drugs Type  : FDA
  • Date : 14th Jul 2015 07:08 am
  • Brand Name : Zenapax
  • Generic Name : daclizumab (Pronunciation: dah KLIH zyoo mab)
Descriptions

ZENAPAX (daclizumab) is an immunosuppressive, humanized IgG1 monoclonal antibody produced by recombinant DNA technology that binds specifically to the alpha subunit (p55 alpha, CD25, or Tac subunit) of the human high-affinity interleukin-2 (IL-2) receptor that is expressed on the surface of activated lymphocytes.

Daclizumab is a composite of human (90%) and murine (10%) antibody sequences. The human sequences were derived from the constant domains of human IgG1 and the variable framework regions of the Eu myeloma antibody. The murine sequences were derived from the complementarity-determining regions of a murine anti-Tac antibody. The molecular weight predicted from the DNA sequence is 144 kilodaltons.

ZENAPAX (daclizumab) 25 mg/5 mL is supplied as a clear, sterile, colorless concentrate for further dilution and intravenous administration. Each milliliter of ZENAPAX contains 5 mg of daclizumab and 3.6 mg sodium phosphate monobasic monohydrate, 11 mg sodium phosphate dibasic heptahydrate, 4.6 mg sodium chloride, 0.2 mg polysorbate 80, and may contain hydrochloric acid or sodium hydroxide to adjust the pH to 6.9. No preservatives are added.

What are the possible side effects of daclizumab (Zenapax)?

There may be an increased risk of infection with the use of daclizumab. Contact your doctor immediately if you develop signs of infection such as fever or chills; sore throat, coughing, congestion or other signs of infection; redness, pain, or swelling of a skin wound; or burning or difficult urination.

Treatment with an immunosuppressant such as daclizumab may increase the risk of developing certain types of cancer (e.g., lymphoma). Talk to your doctor about the risks and benefits of using this medication.

If you experience a serious allergic reaction (difficulty breathing;...

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What are the precautions when taking daclizumab (Zenapax)?

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Indications

ZENAPAX (daclizumab) is indicated for the prophylaxis of acute organ rejection in patients receiving renal transplants. It is used as part of an immunosuppressive regimen that includes cyclosporine and corticosteroids.

The efficacy of ZENAPAX (daclizumab) for the prophylaxis of acute rejection in recipients of other solid organ allografts has not been demonstrated.

Dosage Administration

ZENAPAX (daclizumab) is used as part of an immunosuppressive regimen that includes cyclosporine and corticosteroids. The recommended dose for ZENAPAX (daclizumab) in adult and pediatric patients is 1.0 mg/kg (see PRECAUTIONS: Pediatric Use). The calculated volume of ZENAPAX (daclizumab) should be mixed with 50 mL of sterile 0.9% sodium chloride solution and administered via a peripheral or central vein over a 15-minute period.

Based on the clinical trials, the standard course of ZENAPAX (daclizumab) therapy is five doses. The first dose should be given no more than 24 hours before transplantation. The four remaining doses should be given at intervals of 14 days.

No dosage adjustment is necessary for patients with severe renal impairment. No dosage adjustments based on other identified covariates (age, gender, proteinuria, race) are required for renal allograft patients. No data are available for administration in patients with severe hepatic impairment.

Instructions for Administration

  • ZENAPAX (daclizumab) IS NOT FOR DIRECT INJECTION. The calculated volume should be diluted in 50 mL of sterile 0.9% sodium chloride solution before intravenous administration to patients. When mixing the solution, gently invert the bag in order to avoid foaming; DO NOT SHAKE.
  • Parenteral drug products should be inspected visually for particulate matter and discoloration before administration. If particulate matter is present or the solution colored, do not use.
  • Care must be taken to assure sterility of the prepared solution, since the drug product does not contain any antimicrobial preservative or bacteriostatic agents.
  • ZENAPAX (daclizumab) is a colorless solution provided as a single-use vial; any unused portion of the drug should be discarded.
  • Once the infusion is prepared, it should be administered intravenously within 4 hours. If it must be held longer, it should be refrigerated between 2° to 8°C (36° to 46°F) for up to 24 hours. After 24 hours, the prepared solution should be discarded.
  • No incompatibility between ZENAPAX (daclizumab) and polyvinyl chloride or polyethylene bags or infusion sets has been observed. No data are available concerning the incompatibility of ZENAPAX (daclizumab) with other drug substances. Other drug substances should not be added or infused simultaneously through the same intravenous line.
  • ZENAPAX (daclizumab) should only be administered by healthcare personnel trained in the administration of the drug who have available adequate laboratory and supportive medical resources.

How Supplied

ZENAPAX (daclizumab) is supplied in single-use glass vials. Each vial contains 25 mg of daclizumab in5 mL of solution (NDC 0004-0501-09). Vials should be stored between the temperatures of 2° to 8° C (36° to 46°F); do not shake or freeze. Protect undiluted solution against direct light. Diluted medication is stable for 24 hours at 4°C or for 4 hours at room temperature.

Roche Pharmaceuticals, Hoffmann - La Roche Inc, 340 Kingsland Street, Nutley, New Jersey 07110-1199. Revised: September 2005 Copyright 1999-2005. FDA Rev date: 9/15/2005

Side Effects

Because clinical trials are conducted under widely varying conditions, adverse reactions rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug. Rates observed in clinical studies may not reflect those observed in clinical practice. Adverse reaction information obtained in clinical trials does, however, provide a basis for identifying adverse events that appear to be related to drug use and for approximating the rate of occurrence.

The safety of ZENAPAX (daclizumab) was determined in four clinical studies of renal allograft rejection, three of which were randomized controlled clinical trials, in 629 patients receiving renal allografts of whom 336 received ZENAPAX (daclizumab) and 293 received placebo. All patients received concomitant cyclosporine and corticosteroids. In these clinical trials, ZENAPAX (daclizumab) did not appear to alter the pattern, frequency or severity of known major toxicities associated with the use of immunosuppressive drugs.

The use of ZENAPAX (daclizumab) was associated with a higher incidence of mortality when compared to placebo in a large (n=434) randomized controlled study of patients receiving cardiac transplants (see WARNINGS and Incidence of Infectious Episodes).

Adverse events were reported by 95% of the patients in the placebo-treated group and 96% of the patients in the group treated with ZENAPAX (daclizumab) . The proportion of patients prematurely withdrawn from the combined studies because of adverse events was 8.5% in the placebo-treated group and 8.6% in the group treated with ZENAPAX (daclizumab) .

ZENAPAX (daclizumab) did not increase the number of serious adverse events observed compared with placebo. The most frequently reported adverse events were gastrointestinal disorders, which were reported with equal frequency in ZENAPAX (daclizumab) - (67%) and placebo-treated (68%) patient groups.

The incidence and types of adverse events were similar in both placebo-treated patients and patients treated with ZENAPAX (daclizumab) . The following adverse events occurred in ≥ 5% of patients treated with ZENAPAX (daclizumab) . These events included: Gastrointestinal System: constipation, nausea, diarrhea, vomiting, abdominal pain, pyrosis, dyspepsia, abdominal distention, epigastric pain not food-related; Metabolic and Nutritional: edema extremities, edema; Central and Peripheral Nervous System: tremor, headache, dizziness; Urinary System: oliguria, dysuria, renal tubular necrosis; Body as a Whole - General: posttraumatic pain, chest pain, fever, pain, fatigue; Autonomic Nervous System: hypertension, hypotension, aggravated hypertension; Respiratory System: dyspnea, pulmonary edema, coughing; Skin and Appendages: impaired wound healing without infection, acne; Psychiatric: insomnia; Musculoskeletal System: musculoskeletal pain, back pain;Heart Rate and Rhythm: tachycardia; Vascular Extracardiac: thrombosis; Platelet, Bleeding and Clotting Disorders: bleeding; Hemic and Lymphatic: lymphocele.

The following adverse events occurred in < 5% and ≥ 2% of patients treated with ZENAPAX (daclizumab) . These included: Gastrointestinal System: flatulence, gastritis, hemorrhoids;

Metabolic and Nutritional: fluid overload, diabetes mellitus, dehydration; Urinary System: renal damage, hydronephrosis, urinary tract bleeding, urinary tract disorder, renal insufficiency; Body as a Whole - General: shivering, generalized weakness; Central and Peripheral Nervous System: urinary retention, leg cramps, prickly sensation; Respiratory System: atelectasis, congestion, pharyngitis, rhinitis, hypoxia, rales, abnormal breath sounds, pleural effusion; Skin and Appendages: pruritus, hirsutism, rash, night sweats, increased sweating; Psychiatric: depression, anxiety; Musculoskeletal System: arthralgia, myalgia; Vision: vision blurred; Application Site: application site reaction.

Incidence of Malignancies

One and 3 years posttransplant, the incidence of malignancies was 2.7% and 7.8%, respectively, in the placebo group compared with 1.5% and 6.4%, respectively, in the ZENAPAX (daclizumab) group. Addition of ZENAPAX (daclizumab) did not increase the number of posttransplant lymphomas up to 3 years posttransplant. Lymphomas occurred at a frequency of ≤ 1.5% in both placebo-treated and ZENAPAX (daclizumab) -treated groups.

Hyperglycemia

No differences in abnormal hematologic or chemical laboratory test results were seen between groups treated with placebo or ZENAPAX (daclizumab) with the exception of fasting blood glucose. Fasting blood glucose was measured in a small number of patients treated with placebo or ZENAPAX (daclizumab) . A total of 16% (10 of 64 patients) of placebo-treated and 32% (28 of 88 patients) of patients treated with ZENAPAX (daclizumab) had high fasting blood glucose values. Most of these high values occurred either on the first day posttransplant when patients received high doses of corticosteroids or in patients with diabetes.

Incidence of Infectious Episodes

The overall incidence of infectious episodes, including viral infections, fungal infections, bacteremia and septicemia, and pneumonia, was not higher in patients treated with ZENAPAX (daclizumab) than in placebo-treated patients in trials of renal transplantation. In a large randomized study of ZENAPAX (daclizumab) used for the prevention of allograft rejection in patients receiving cardiac allografts, more patients receiving ZENAPAX (daclizumab) experienced severe or fatal infections after 12 months of therapy when compared to those receiving placebo (10% vs 7%, respectively). The risks of infection or death may be increased in patients receiving concomitant anti-lymphocyte antibody therapy (see WARNINGS).

The types of infections reported in trials of renal transplantation were similar in both the ZENAPAX (daclizumab) -treated and the placebo-treated groups. Cytomegalovirus infection was reported in 16% of the patients in the placebo group and 13% of the patients in the ZENAPAX (daclizumab) group. One exception was cellulitis and wound infections, which occurred in 4.1% of placebo-treated patients and 8.4% of patients treated with ZENAPAX (daclizumab) . At 1 year posttransplant, 7 placebo patients and 1 patient treated with ZENAPAX (daclizumab) had died of an infection. At 3 years posttransplant, 8 placebo patients and 4 patients treated with ZENAPAX (daclizumab) had died of infection.

Immunogenicity

Low titers of anti-idiotype antibodies to daclizumab were detected in the adult patients treated with ZENAPAX (daclizumab) with an overall incidence of 14%. The incidence of anti-daclizumab antibodies observed in the pediatric patients was 34%. No antibodies that affected efficacy, safety, serum daclizumab levels or any other clinically relevant parameter examined were detected. The data reflect the percentage of patients whose test results were considered positive for antibodies to daclizumab in an ELISA assay and are highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in the assay may be influenced by several factors including sample handling, timing of sample collection, concomitant medications and underlying disease. For these reasons, comparison of the incidence of antibodies to daclizumab with the incidence of antibodies to other products may be misleading.

Post-Marketing Experience

The following adverse reactions have been identified and reported during post-approval use of ZENAPAX (daclizumab). Because the reports of these reactions are voluntary and the population is of uncertain size, it is not always possible to reliably estimate the frequency of the reaction or establish a causal relationship to drug exposure.

Severe acute hypersensitivity reactions including anaphylaxis characterized by hypotension, bronchospasm, wheezing, laryngeal edema, pulmonary edema, cyanosis, hypoxia, respiratory arrest, cardiac arrhythmia, cardiac arrest, peripheral edema, loss of consciousness, fever, rash, urticaria, diaphoresis, pruritus, and/or injection site reactions, as well as cytokine release syndrome, have been reported during post-marketing experience with ZENAPAX (daclizumab) . The relationship between these reactions and the development of antibodies to ZENAPAX (daclizumab) is unknown.

Interactions

The following medications have been administered with ZENAPAX (daclizumab) in clinical trials in renal allograft patients with no incremental increase in adverse reactions: cyclosporine, mycophenolate mofetil, ganciclovir, acyclovir, azathioprine, and corticosteroids. Very limited experience exists in these patients with the use of ZENAPAX (daclizumab) concomitantly with tacrolimus, muromonab-CD3, antithymocyte globulin, and anti-lymphocyte globulin.

In renal allograft recipients (n=50) treated with ZENAPAX (daclizumab) and mycophenolate mofetil, no pharmacokinetic interaction between ZENAPAX (daclizumab) and mycophenolic acid, the active metabolite of mycophenolate mofetil, was observed.

However, in a large clinical study in cardiac transplant recipients (n=434), the use of ZENAPAX (daclizumab) as part of an immunosuppression regimen including cyclosporine, mycophenolate mofetil, and corticosteroids was associated with an increase in mortality, particularly in patients receiving concomitant anti-lymphocyte antibody therapy and in patients who developed severe infections (see WARNINGS and ADVERSE REACTIONS: Incidence of Infectious Episodes).

Warnings

(see Boxed WARNING)

The use of ZENAPAX (daclizumab) as part of an immunosuppressive regimen including cyclosporine, mycophenolate mofetil, and corticosteroids may be associated with an increase in mortality. In a randomized, double-blind, placebo-controlled trial of ZENAPAX (daclizumab) for the prevention of allograft rejection in 434 cardiac transplant recipients receiving concomitant cyclosporine, mycophenolate mofetil, and corticosteroids, mortality at 6 and 12 months was increased in those patients receiving ZENAPAX (daclizumab) compared to those receiving placebo (7% vs 5%, respectively at 6 months; 10% vs 6%respectively at 12 months). Some, but not all, of the increase in mortality appeared related to a higher incidence of severe infections. Concomitant use of anti-lymphocyte antibody therapy may also be a factor in some of the fatal infections.

ZENAPAX (daclizumab) should be administered under qualified medical supervision. Patients should be informed of the potential benefits of therapy and the risks associated with administration of immunosuppressive therapy.

While the incidence of lymphoproliferative disorders and opportunistic infections in the limited clinical trial experience was no higher in patients treated with ZENAPAX (daclizumab) compared with placebo-treated patients, patients on immunosuppressive therapy are at increased risk for developing lymphoproliferative disorders and opportunistic infections and should be monitored accordingly.

Hypersensitivity

Severe, acute (onset within 24 hours) hypersensitivity reactions including anaphylaxis have been observed both on initial exposure to ZENAPAX (daclizumab) and following re-exposure. These reactions may include hypotension, bronchospasm, wheezing, laryngeal edema, pulmonary edema, cyanosis, hypoxia, respiratory arrest, cardiac arrhythmia, cardiac arrest, peripheral edema, loss of consciousness, fever, rash, urticaria, diaphoresis, pruritus, and/or injection site reactions. If a severe hypersensitivity reaction occurs, therapy with ZENAPAX (daclizumab) should be permanently discontinued. Medications for the treatment of severe hypersensitivity reactions including anaphylaxis should be available for immediate use. Patients previously administered ZENAPAX (daclizumab) should only be re-exposed to a subsequent course of therapy with caution. The potential risks of such re-administration, specifically those associated with immunosuppression, are not known.

Precautions

General

It is not known whether ZENAPAX (daclizumab) use will have a long-term effect on the ability of the immune system to respond to antigens first encountered during ZENAPAX (daclizumab) -induced immunosuppression.

Re-administration of ZENAPAX (daclizumab) after an initial course of therapy has not been studied in humans. The potential risks of such re-administration, specifically those associated with immunosuppression and/or the occurrence of anaphylaxis/anaphylactoid reactions, are not known.

Carcinogenesis, Mutagenesis and Impairment of Fertility

Long-term studies to evaluate the carcinogenic potential of ZENAPAX (daclizumab) have not been performed. ZENAPAX (daclizumab) was not genotoxic in the Ames or the V79 chromosomal aberration assays, with or without metabolic activation. The effect of ZENAPAX (daclizumab) on fertility is not known, because animal reproduction studies have not been conducted with ZENAPAX (see WARNINGS and ADVERSE REACTIONS).

Pregnancy

Pregnancy Category C: A preclinical developmental toxicity study with ZENAPAX (daclizumab) has shown an increased risk of early prenatal loss in cynomolgus monkeys compared to placebo. However, the clinical experience of ZENAPAX (daclizumab) exposed pregnancies is still limited. In general, IgG molecules are known to cross the placental barrier. ZENAPAX (daclizumab) should not be used in pregnant women unless the potential benefit justifies the potential risk to the fetus. Women of childbearing potential should use effective contraception before beginning ZENAPAX (daclizumab) therapy, during therapy, and for 4 months after completion of ZENAPAX (daclizumab) therapy.

Nursing Mothers

It is not known whether ZENAPAX (daclizumab) is excreted in human milk. However, in preclinical developmental toxicity studies with ZENAPAX (daclizumab) , four out of seven lactating cynomolgus monkeys given a 5-10 fold multiple (10mg/kg) of the normal human dose were found to secrete very low levels of ZENAPAX (daclizumab) (0.17 – 0.28% of maternal serum levels) in breast milk. Because many drugs are excreted in human milk, including human antibodies, and because of the potential for adverse reactions, a decision should be made to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and effectiveness of ZENAPAX (daclizumab) have been established in pediatric patients from 11 months to 17 years of age. Use of ZENAPAX (daclizumab) in this age group is supported by evidence from adequate and well-controlled studies of ZENAPAX (daclizumab) in adults with additional pediatric pharmacokinetic data (see CLINICAL PHARMACOLOGY). Data from the pediatric pharmacokinetic study were also analyzed for efficacy, immunogenicity and safety. In an open-label study, 60 pediatric renal transplant recipients [median age of 10 years] received standard immunosuppressive agents in addition to a regimen of ZENAPAX (daclizumab) administered at a dose of 1.0 mg/kg at intervals of 14 days for a total of 5 doses, starting immediately before transplantation. In this study, the combined incidence of biopsy-proven and clinically presumptive acute rejection at 1 year posttransplant was 17% (10/60). Patient and graft survival at 1 year posttransplant were 100% and 96.7%, respectively. The incidence of anti-daclizumab antibodies (34%) observed in the first 3 months posttransplant was higher than the incidence previously observed in adult patients (14%) (see ADVERSE REACTIONS: Immunogenicity).

The safety profile of ZENAPAX (daclizumab) in pediatric transplant patients was shown to be comparable with that in adult transplant patients with the exception of the following adverse events, which occurred more frequently in pediatric patients ( > 15% difference in incidence): diarrhea, post-operative pain, fever, vomiting, aggravated hypertension, pruritus, and infections of the upper respiratory tract and urinary tract.

It is not known whether the immune response to vaccines, infection, and other antigenic stimuli administered or encountered during ZENAPAX (daclizumab) therapy is impaired or whether such response will remain impaired after ZENAPAX therapy.

Also see CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION.

Geriatric Use

Clinical studies of ZENAPAX (daclizumab) did not include sufficient numbers of subjects age 65 and older to determine whether they respond differently from younger subjects. Caution must be used in giving immunosuppressive drugs to elderly patients.

OverDose

There have not been any reports of overdoses with ZENAPAX (daclizumab) . A maximum tolerated dose has not been determined in patients. A dose of 1.5 mg/kg has been administered to bone marrow transplant recipients without any associated adverse events.

ContrainDications

ZENAPAX (daclizumab) is contraindicated in patients with known hypersensitivity to daclizumab or

to any components of this product.

Clinical Pharamacology

General

Mechanism of Action

Daclizumab functions as an IL-2 receptor antagonist that binds with high-affinity to the Tac subunit of the high-affinity IL-2 receptor complex and inhibits IL-2 binding. Daclizumab binding is highly specific for Tac, which is expressed on activated but not resting lymphocytes. Administration of ZENAPAX (daclizumab) inhibits IL-2-mediated activation of lymphocytes, a critical pathway in the cellular immune response involved in allograft rejection.

While in the circulation, ZENAPAX (daclizumab) impairs the response of the immune system to antigenic challenges. Whether the ability to respond to repeated or ongoing challenges with those antigens returns to normal after ZENAPAX is cleared is unknown (see PRECAUTIONS).

Pharmacokinetics

Adults

In clinical trials involving renal allograft patients treated with a 1 mg/kg IV dose of ZENAPAX (daclizumab) every 14 days for a total of five doses, peak serum concentration (mean ± SD) rose between the first dose (21 ± 14 µg/mL) and fifth dose (32 22 g/mL). The mean trough serum concentration before the fifth dose was 7.6±4.0 µg/mL. Population pharmacokinetic analysis of the data using a two-compartment open model gave the following values for a reference patient (45-year-old male Caucasian patient with a body weight of 80 kg and no proteinuria): systemic clearance = 15 mL/hour, volume of central compartment = 2.5 liter, volume of peripheral compartment = 3.4 liter. The estimated terminal elimination half-life for the reference patient was 20 days (480 hours), which is similar to the terminal elimination half-life for human IgG (18 to 23 days). Bayesian estimates of terminal elimination half-life ranged from 11 to 38 days for the 123 patients included in the population analysis. The influence of body weight on systemic clearance supports the dosing of ZENAPAX (daclizumab) on a milligram per kilogram (mg/kg) basis. For patients studied, this dosing maintained drug exposure within 30% of the reference exposure. Covariate analyses showed that no dosage adjustments based on age, race, gender or degree of proteinuria, are required for renal allograft patients. The estimated interpatient variability (percent coefficient of variation) in systemic clearance and central volume of distribution were 15% and 27%, respectively.

Pediatrics

Pharmacokinetic parameters were evaluated in 61 pediatric patients treated with a 1 mg/kg IV dose of ZENAPAX (daclizumab) every 14 days for a total of five doses. Peak serum concentration (mean ± SD) rose between the first dose (16±12 µg/mL) and fifth dose (21 ± 14 µg/mL). The mean trough serum concentration before the fifth dose was 5.0 ± 2.7 µg/mL. Population pharmacokinetic analysis of the data using a two-compartment open model gave the following values for a reference patient (Caucasian patient with a body weight of 29.7 kg): systemic clearance = 10 mL/hour, volume of central compartment = 2.0 liter, volume of peripheral compartment = 1.4 liter. The estimated terminal elimination half-life for the reference patient was 13 days (317 hours). For the patients studied, this dosing maintained drug exposure within 50% of the reference exposure. Covariate analyses suggested that disposition parameters were not influenced to a clinically relevant extent by race, gender or degree of proteinuria. The estimated interpatient variability (percent coefficient of variation) in systemic clearance and central volume of distribution were 30% and 40%, respectively.

Pharmacodynamics

In vitro and in vivo data suggest that serum levels of 5 to 10 µg/mL are necessary for saturation of the Tac subunit of the IL-2 receptors to block the responses of activated T lymphocytes. At the recommended dosage regimen, daclizumab saturates the Tac subunit of the IL-2 receptor for approximately 90 and 120 days posttransplant, respectively in pediatric and adult patients. The duration of clinically significant IL-2 receptor blockade after the recommended course of ZENAPAX (daclizumab) is not known. No significant changes to circulating lymphocyte numbers or cell phenotypes were observed by flow cytometry. Cytokine release syndrome has not been observed after ZENAPAX (daclizumab) administration.

Clinical Studies

The safety and efficacy of ZENAPAX (daclizumab) for the prophylaxis of acute organ rejection in adult patients receiving their first cadaveric kidney transplant were assessed in two randomized, double-blind, placebo-controlled, multicenter trials. These trials compared a dose of 1.0 mg/kg of ZENAPAX (daclizumab) with placebo when each was administered as part of standard immunosuppressive regimens containing either cyclosporine and corticosteroids (double-therapy trial, no US sites) or cyclosporine, corticosteroids, and azathioprine (triple-therapy trial, predominantly US sites) to prevent acute renal allograft rejection. ZENAPAX (daclizumab) dosing was initiated within 24 hours pretransplant, with subsequent doses given every 14 days for a total of five doses.

The primary efficacy endpoint of both trials was the proportion of patients who developed a biopsy-proven acute rejection episode within the first 6 months following transplantation. As shown in Table 1, this incidence was significantly lower in the group treated with ZENAPAX (daclizumab) in both the double-therapy and triple-therapy trials.

Table 1: Efficacy Parameters

  Triple-therapy Regimen (cyclosporine, corticosteroids, and azathioprine) Double-therapy Regimen (cyclosporine and corticosteroids)
  Placebo (N=134) ZENAPAX (N=126) p-value Placebo (N=134) ZENAPAX (N=141) p-value
Incidence of biopsy-provenacute rejection at 6 months
  No. of patients 47 (35%) 28 (22%) 0.03 63 (47%) 39 (28%) 0.001
Incidence of biopsy-provenacute rejection at 1 year
  No. of patients 51 (38%) 35 (28%) n.s. 65 (49%) 39 (28%) <0.001
Graft survival at 3 years post transplant
  No. of patients with functioning graft 111 (83%) 106 (84%) n.s. 105 (78%) 116 (82%) n.s.
Patient survival at3 years post transplant
  No. of patients 126 (94%) 116 (92%) n.s. 118 (88%) 135 (96%) 0.02
n.s. = not significant

Treatment with ZENAPAX (daclizumab) was associated with better patient survival up to 3 years posttransplant in the double-therapy study. No difference in patient survival was observed in the triple-therapy study between patients treated with ZENAPAX (daclizumab) or placebo up to 3 years posttransplant. No difference was observed for graft survival between treatment groups in both studies at 3 years posttransplant.

The incidence of delayed graft function was not different between patients treated with placebo or ZENAPAX (daclizumab) in either study. No difference in graft function was observed 1 year and 3 years posttransplant in either study between patients treated with placebo or ZENAPAX (daclizumab) .

In a randomized, double-blind study to assess tolerability, pharmacokinetics, and drug interactions in renal allograft recipients, ZENAPAX (daclizumab) (50 patients) or placebo (25 patients) was added to an immunosuppressive regimen of cyclosporine, mycophenolate mofetil, and corticosteroids. In this study, the addition of ZENAPAX (daclizumab) did not result in an increased incidence of adverse events or a change in the types of adverse events reported. The incidence of the combined endpoint of biopsy-proven or clinically presumptive acute rejection was 20% (5 of 25 patients) in the placebo group and 12% (6 of 50 patients) in the ZENAPAX (daclizumab) group. Although numerically lower, the difference in acute rejection was not significant. However, in a randomized, double-blind, placebo-controlled trial of ZENAPAX (daclizumab) in cardiac transplant recipients (n = 434) receiving concomitant cyclosporine, mycophenolate mofetil, and corticosteroids, mortality was increased in patients randomized to receive ZENAPAX (daclizumab) compared with those randomized to receive placebo (see WARNINGS and ADVERSE REACTIONS).

Patient Information

No information provided. Please refer to the WARNINGS and PRECAUTIONS sections.

Consumer Overview Uses

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

 

NO MONOGRAPH AVAILABLE AT THIS TIME

 

USES: Consult your pharmacist.

 

HOW TO USE: Consult your pharmacist.

Consumer Overview Side Effect

SIDE EFFECTS: Consult your pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Consumer Overview Missed Dose

DRUG INTERACTIONS: Consult your pharmacist.

Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

 

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call their local poison control center at 1-800-222-1222. Canada residents can call a provincial poison control center.

 

NOTES: No monograph available at this time.

 

MISSED DOSE: Consult your pharmacist.

 

STORAGE: Consult your pharmacist.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

 

Information last revised March 2013. Copyright(c) 2013 First Databank, Inc.

Patient Detailed Side Effect

Brand Names: Zenapax

Generic Name: daclizumab (Pronunciation: dah KLIH zyoo mab)

  • What is daclizumab (Zenapax)?
  • What are the possible side effects of daclizumab (Zenapax)?
  • What is the most important information I should know about daclizumab (Zenapax)?
  • What should I discuss with my healthcare provider before using daclizumab (Zenapax)?
  • How should I use daclizumab (Zenapax)?
  • What happens if I miss a dose (Zenapax)?
  • What happens if I overdose (Zenapax)?
  • What should I avoid while using daclizumab (Zenapax)?
  • What other drugs will affect daclizumab (Zenapax)?
  • Where can I get more information?

What is daclizumab (Zenapax)?

Daclizumab is an immunosuppressant. Immunosuppressants decrease the actions of the body's immune system.

Daclizumab is used to prevent the body from rejecting a transplanted kidney. Daclizumab is usually used as part of a treatment regimen including other medications.

Daclizumab may also be used for purposes other than those listed in this medication guide.

What are the possible side effects of daclizumab (Zenapax)?

There may be an increased risk of infection with the use of daclizumab. Contact your doctor immediately if you develop signs of infection such as fever or chills; sore throat, coughing, congestion or other signs of infection; redness, pain, or swelling of a skin wound; or burning or difficult urination.

Treatment with an immunosuppressant such as daclizumab may increase the risk of developing certain types of cancer (e.g., lymphoma). Talk to your doctor about the risks and benefits of using this medication.

If you experience a serious allergic reaction (difficulty breathing; closing of the throat; swelling of the lips, tongue, or face; or hives) to daclizumab, seek emergency medical attention.

Other, less serious side effects may also occur. Continue to use daclizumab and notify your doctor if you experience

  • upset stomach, nausea, or vomiting;
  • diarrhea or constipation;
  • tremor or dizziness;
  • headache; or
  • swelling of the hands, feet or legs.

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially bothersome. You may report side effects to FDA at 1-800-FDA-1088.

Read the Zenapax (daclizumab) Side Effects Center for a complete guide to possible side effects

Learn More »

What is the most important information I should know about daclizumab (Zenapax)?

Because it may cause serious side effects, daclizumab should only be prescribed by a doctor experienced in immunosuppressive therapy and the management of organ transplant patients. Discuss the risks and benefits of using this medication with your doctor.

There may be an increased risk of infection with the use of daclizumab. Contact your doctor immediately if you develop signs of infection such as fever or chills; sore throat, coughing, congestion or other signs of infection; redness, pain, or swelling of a skin wound; or burning or difficult urination.

Treatment with an immunosuppressant such as daclizumab may increase the risk of developing certain types of cancer (e.g., lymphoma). Talk to your doctor about the risks and benefits of using this medication.

Patient Detailed How Take

What should I discuss with my healthcare provider before using daclizumab (Zenapax)?

Because it may cause serious side effects, daclizumab should only be prescribed by a doctor experienced in immunosuppressive therapy and the management of organ transplant patients. Discuss the risks and benefits of using this medication with your doctor.

Before using daclizumab, tell your doctor if you

  • have used daclizumab in the past;
  • have had a previous allergic reaction to daclizumab;
  • have any active or chronic viral, bacterial, or fungal infection; or
  • have a suppressed immune system or take medications that may suppress the immune system (e.g., medicines to prevent rejection of a transplanted organ, some cancer medicines, others).

You may not be able to use daclizumab, or you may require a dosage adjustment or special monitoring if you have any of the conditions listed above.

Daclizumab is in the FDA pregnancy category C. This means that it is not known whether daclizumab will be harmful to an unborn baby. Do not use this medication without first talking to your doctor if you are pregnant or could become pregnant during treatment. For women who could become pregnant, contraception is recommended before starting, during, and for four months following treatment with daclizumab to ensure protection from pregnancy.

It is not known whether daclizumab passes into breast milk. Do not use daclizumab without first talking to your doctor if you are breast-feeding a baby.

How should I use daclizumab (Zenapax)?

Daclizumab is administered as an intravenous (into the vein) injection. In most cases, your healthcare provider will administer daclizumab in a hospital or clinic setting. If you are using daclizumab at home, your healthcare provider will give you detailed instructions regarding preparation, administration, and storage of the medication.

The first dose of daclizumab is usually administered within 24 hours of the kidney transplant. Four additional doses are then given at 14 day intervals following transplantation.

When mixing the solution for injection, the bag should be gently inverted to ensure mixing. Do not shake the mixture.

After mixing the solution for injection, it should be used within 4 hours. If the mixture cannot be used within 4 hours, it should be refrigerated between 36 and 46 degrees Fahrenheit (2 and 8 degrees Celsius) for up to 24 hours. If it is not used within 24 hours, it must be discarded.

Do not use any solution that is discolored or that has particles in it.

Your doctor may want you to have blood tests or other medical evaluations during treatment with daclizumab to monitor progress and side effects.

Your healthcare provider will store daclizumab as directed by the manufacturer. If you are using daclizumab at home, your healthcare provider will give you detailed storage instructions.

Patient Detailed Avoid Taking

What happens if I miss a dose (Zenapax)?

Contact your doctor if you miss a dose of daclizumab.

What happens if I overdose (Zenapax)?

Seek emergency medical attention if an overdose is suspected.

Symptoms of a daclizumab overdose are not known.

What should I avoid while using daclizumab (Zenapax)?

Daclizumab can lower the activity of the immune system making you susceptible to infections. Avoid contact with people who have colds, the flu, or other contagious illnesses. Contact your doctor immediately if you develop any signs of illness or infection.

Talk to your doctor before receiving any vaccines during treatment with daclizumab. Some vaccines may not be effective, or may be harmful, if received during treatment with daclizumab. In addition, avoiding close contact with people who have recently been vaccinated with a "live" vaccine (e.g. oral polio vaccine, nasal influenza vaccine) may be recommended. There is a chance that the virus can be passed on to you.

Tell your doctor and dentist that you are using this medication before having surgery and before starting any other medicines.

What other drugs will affect daclizumab (Zenapax)?

Talk to your doctor before receiving any vaccines during treatment with daclizumab. Some vaccines may not be effective, or may be harmful, if received during treatment with daclizumab. In addition, avoiding close contact with people who have recently been vaccinated with a "live" vaccine (e.g. oral polio vaccine, nasal influenza vaccine) may be recommended. There is a chance that the virus can be passed on to you.

Drugs other than those listed here may also interact with daclizumab. Talk to your doctor and pharmacist before taking any prescription or over-the-counter medicines, including vitamins, minerals, and herbal products.

Where can I get more information?

Your pharmacist has additional information about daclizumab written for health professionals that you may read.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

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