daclizumab (Rx)

Brand and Other Names:Zinbryta
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

solution for injection

  • 150mg/mL in a single-dose prefilled syringe

Multiple Sclerosis

Indicated for adults with relapsing forms of multiple sclerosis (MS)

150 mg SC once monthly (see Administration)

Dosage Modifications

Preexisting hepatic impairment including ALT/AST ≥2 x ULN: Contraindicated

Elevated liver enzymes during treatment

  • Lab values
    • ALT/AST >5 x ULN, OR
    • Total bilirubin >2 x ULN, OR
    • ALT/AST ≥3 but <5 x ULN and total bilirubin &1.5 bu <2 x ULN

Recommendations

  • Interrupt daclizumab therapy and investigate for other etiologies of abnormal lab value(s)
  • If no other etiologies identified, then discontinue daclizumab
  • If other etiologies are identified, reassess overall risk-benefit profile of daclizumab and consider whether to resume drug when both AST or ALT are <2 x ULN and total bilirubin is ≤ULN
  • In clinical trials, permanent discontinuation of therapy was required if the patient had liver test abnormalities resulting in suspension of study treatment for at least 8 consecutive weeks

Dosing Considerations

Because of its safety profile (ie, risk of hepatic injury and immune-mediated disorders), daclizumab is generally reserved for patients who have inadequate response to ≥2 other drugs for MS

Assessment prior to initiating

  • Hepatic assessment
    • Evaluate serum transaminases (ALT, AST) and total bilirubin levels
    • Initiation is contraindicated with preexisting hepatic disease or hepatic impairment including ALT or AST ≥2 x ULN (see Contraindications)
  • Assess for tuberculosis (TB) and other infections
    • Evaluate patients at high risk for TB prior to initiating treatment
    • For patients testing positive for TB, treat TB by standard medical practice prior to therapy with daclizumab
    • Avoid initiating in patients with TB or other severe active infection (see Cautions)
    • Prior to initiation, screen patients for Hepatitis B and C (contraindicated with preexisting hepatic disease)
  • Vaccinations
    • Vaccination with live vaccines is not recommended during treatment and up to 4 months after discontinuation of treatment
    • Consider any necessary immunization with live vaccines prior to treatment

Laboratory testing and monitoring

  • Test transaminase levels and total bilirubin monthly and assess before the next dose of daclizumab; follow transaminase levels and total bilirubin monthly for 6 months after the last dose

<17 years: Safety and efficacy not established

Not recommended in pediatric patients due to the risks of hepatic injury and immune-mediated disorders

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Interactions

Interaction Checker

and daclizumab

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            Immune-mediated disorders (28-32%)

            Nasopharyngitis (25%)

            Skin reactions (19%)

            Upper respiratory tract infection (9-17%)

            Rash (9-11%)

            1-10%

            Influenza (9%)

            Oropharyngeal pain (8%)

            Bronchitis (7%)

            Depression (7%)

            Pharyngitis (6%)

            Increased ALT or AST >5 x ULN (4-6%)

            Eczema (5%)

            Lymphadenopathy (5%)

            Rhinitis (4%) Tonsillitis (4%)

            Anemia (3%)

            Pyrexia (3%)

            Dermatitis (3%)

            Acne (3%)

            Seizures (1%)

            <1%

            Serious drug-related hepatic injury (0.7%)

            Autoimmune hepatitis (0.3%)

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            Warnings

            Black Box Warnings

            Hepatic injury

            • Can cause severe liver injury including life-threatening events, liver failure, and autoimmune hepatitis
            • In clinical trials, 1 patient died due to autoimmune hepatitis
            • Liver injury, including autoimmune hepatitis, can occur at any time during treatment, with cases reported up to 4 months after the last dose
            • Contraindicated with preexisting hepatic disease or hepatic impairment
            • Before initiating, obtain serum transaminases (ALT and AST) and bilirubin levels
            • Test transaminase levels and total bilirubin monthly and assess before the next dose of daclizumab; follow transaminase levels and total bilirubin monthly for 6 months after the last dose
            • In case of elevation in transaminases or total bilirubin, treatment interruption or discontinuation may be required

            Other immune-mediated disorders

            • In addition to autoimmune hepatitis, immune-mediated disorders (eg, skin reactions, lymphadenopathy, noninfectious colitis) can occur
            • Overall, serious immune-mediated conditions were observed in 5% of treated patients
            • If a serious immune-mediated disorder develops, consider stopping daclizumab and refer the patient to a specialist to ensure comprehensive diagnostic evaluation and appropriate treatment

            Treating autoimmune hepatitis or other immune-mediated disorders

            • Some patients required systemic corticosteroids or other immunosuppressant treatment for autoimmune hepatitis or other immune-mediated disorders and continued this treatment after the last dose of daclizumab

            Restricted access program

            • Because of the risks of hepatic injury, including autoimmune hepatitis, and other immune-mediated disorders, daclizumab is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ZINBRYTA REMS Program

            Contraindications

            Preexisting hepatic disease or hepatic impairment, including ALT or AST at least 2 x ULN; daclizumab exacerbate existing liver dysfunction (see Black Box Warnings)

            History of autoimmune hepatitis or other autoimmune condition involving the liver (see Black Box Warnings)

            History of hypersensitivity; use may result in anaphylaxis or life-threatening multiorgan hypersensitivity

            Cautions

            Can cause life-threatening severe liver injury, including liver failure and autoimmune hepatitis (see Black Box Warnings, Contraindications, and Dosage Modifications); liver failure can occur at any time during treatment even with monthly liver enzyme monitoring indicating normal values prior to each dose; liver injury has been reported up to 5 months after last dose; some cases of liver injury may be associated with fever, skin rash, or other immune-mediated disorders

            Immune-mediated disorders reported, including autoimmune hepatitis, skin reactions, lymphadenopathy, and noninfectious colitis (see Black Box Warnings, Contraindications)

            Patients with history of skin conditions, including eczema or psoriasis, the drug may exacerbate those conditions; in addition to serious cases of dermatitis, eczema, psoriasis and drug eruptions, cases of erythema multiforme, erythema nodosum, exfoliative rash, and oral ulcers occurred in clinical trials; treatment of skin reactions included treatment with topical or systemic corticosteroids or immunosuppressant drugs, including tacrolimus

            Consider discontinuing therapy and referring patients who develop symptoms of colitis (e.g., abdominal pain, fever, prolonged diarrhea, bloody stools) to a specialist

            Available only through a restricted access program (see Black Box Warnings)

            Hemolytic anemia reported across all clinical studies (controlled and open-label); if a patient develops signs or symptoms of autoimmune hemolytic anemia, consider discontinuing therapy and referring to appropriate specialist for further evaluation and treatment

            Can cause anaphylaxis, angioedema, and urticaria after the first dose or at any time during treatment; discontinue and do not restart if anaphylaxis or other allergic reactions occur (see Contraindications)

            Increased risk for infection; avoid initiating in patients with severe active infection until infection is fully controlled; assess for preexisting infections (eg, TB, hepatitis B or C) before initiating

            Depression-related events occurred more frequently in patients receiving daclizumab compared with control or placebo in clinical trials; caution in patients with history of depression and/or suicidal ideation; consider discontinuing is severe depression occurs

            Drug interaction overview

            • Caution should be used if hepatotoxic drugs are coadministered, including nonprescription products
            • Avoid use of herbal products or dietary supplements that can cause hepatotoxicity
            • Vaccination with live vaccines is not recommended during treatment and up to 4 months after discontinuation
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            Pregnancy

            Pregnancy

            There are no adequate data on the developmental risk associated with use of daclizumab in pregnant women

            Administration of the drug to monkeys during gestation resulted in embryofetal death and reduced fetal growth at maternal exposures >30 times that expected clinically

            Lactation

            Unknown if distributed in human breast milk

            Daclizumab was excreted in the milk of daclizumab-treated monkeys

            Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

            Humanized monoclonal antibody that binds to the high-affinity interleukin-2 (IL-2) receptor subunit (CD25); these subunits are expressed at high levels on T-cells that become abnormally activated in multiple sclerosis

            Absorption

            Peak plasma time: 5-7 days

            Peak plasma concentration (steady-state): 15 mcg/mL

            AUC (steady-state): 640 mcg·days/mL

            Steady-state reached by fourth dose

            Distribution

            Vd (steady-state): 6.34 L

            Metabolism

            Because it is a protein, daclizumab is expected to undergo catabolism to peptides and amino acids in the same manner as endogenous IgG proteins without renal elimination

            Elimination

            Half-life: 21 days

            Clearance: 0.212 L/day; 19% higher with neutralizing antibodies

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            Administration

            SC Preparation

            Train patients in the proper technique for self-administering SC injections using the prefilled syringe

            30 minutes prior to injection, remove daclizumab from the refrigerator to allow the drug to warm to room temperature

            Do not use external heat sources such as hot water to warm the prefilled syringe

            Do not place daclizumab back into the refrigerator after allowing it to warm to room temperature

            Parenteral drug products should be inspected visually for particulate matter and discoloration

            Solution should appear as colorless to slightly yellow and clear to slightly opalescent

            Do not use if solution is cloudy or there are visible particles

            SC Administration

            For subcutaneous (SC) use only

            Sites for injection include the thigh, abdomen, and back of the upper arm

            Use each prefilled syringe 1 time and then place in a sharps disposal container for disposal according to community guidelines

            Missed dose

            • Instruct patients to inject a missed dose as soon as possible but no more than 2 weeks late
            • After 2 weeks, skip the missed dose and take the next dose on schedule
            • Administer only 1 dose at a time; do not double the dose

            Storage

            Refrigerate between 2-8°C (36-46°F) in the original carton to protect from light

            Do not freeze; discard if frozen

            Do not expose to temperatures >30°C (86°F)

            If refrigeration is unavailable, may store protected from light up to 30°C (86°F) for a period up to 30 days

            Do not place drug back into the refrigerator after allowing it to warm to room temperature

            Discard after 30 days without refrigeration

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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