Does Zinbryta (daclizumab) cause side effects?

Zinbryta (daclizumab) is an interleukin-2 receptor blocking antibody used to treat multiple sclerosis (MS). Its mechanism of action is not completely understood. 

Available data suggest that it may work by modifying immune processes that may be responsible for causing MS by interfering with the activation of lymphocytes (a type of white blood cell) that cause inflammation and destruction of nerves in patients with MS

Zinbryta does not cure MS. It decreases the number of MS flares and lesions. It is reserved for patients who have had an inadequate response to two or more MS drugs because of its safety profile.

Common side effects of Zinbryta include

Serious side effects of Zinbryta include

Drug interactions of Zinbryta include prescription drugs, non-prescription drugs, herbal products, or dietary supplements that affect the liver because it may increase the risk of liver damage. Such combinations should be avoided when possible or used cautiously. 

Zinbryta has not been adequately evaluated in pregnant women. There is no information about the secretion of Zinbryta in breast milk. Consult your doctor before breastfeeding.

What are the important side effects of Zinbryta (daclizumab)?

Common side effects include:

Other side effects include:

Other less common side effects include:

Possible serious side effects include:

  • Liver damage
  • Immune mediated disorders (for example, skin reactions, colitis)
  • Serious allergic reactions (anaphylaxis, angioedema)
  • Severe infections
  • Depression
  • Suicidal thoughts, Suicide
  • Decreased numbers of white blood cells
  • Severe skin reactions
  • Non-infectious colitis

Zinbryta (daclizumab) side effects list for healthcare professionals

The following serious adverse reactions are described elsewhere in labeling:

  • Hepatic Injury
  • Immune-Mediated Disorders
  • Acute Hypersensitivity
  • Infections
  • Depression and Suicide

Clinical Trials Experience

  • Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of Zinbryta cannot be directly compared with rates in clinical trials of other drugs and may not reflect the rates observed in practice.
  • In all controlled and uncontrolled trials performed in patients with relapsing multiple sclerosis, 2236 patients received Zinbryta for a total of 5214 person-years.
  • Of these patients, 1576 received Zinbryta for at least 1 year, 1259 for at least 2 years, and 888 for at least 3 years.
  • In the controlled studies, approximately 67% were female, 92% were Caucasian, and the mean age was 36 years at study entry.
  • In the active-controlled study (Study 1), 919 patients received Zinbryta (150 mg SQ, every 4 weeks) and 922 patients received AVONEX (interferon beta-1a 30 mcg IM, weekly) for a minimum of 2 years and up to 3 years, with 1952 person-years of exposure to Zinbryta; the median length of treatment was approximately 27 months. The adverse reactions from Study 1 are presented in Table 2.
  • In the placebo-controlled study (Study 2), 417 patients received Zinbryta with 423 person-years of exposure, of which 208 received 150 mg, and 204 received placebo every 4 weeks for up to 1 year; the median length of treatment was approximately 11 months. The adverse reactions from Study 2 are presented in Table 3.
  • The most common adverse reactions (incidence at least 5% and at least 2% higher incidence than comparator) that occurred in Zinbryta-treated patients were
  • The most common adverse reactions leading to discontinuation in up to 5% of patients treated with Zinbryta were hepatic events including elevations of serum transaminases and cutaneous events.
  • Patients were excluded from the clinical studies for abnormal laboratory values including hemoglobin, complete blood count with differential, serum transaminases, or serum creatinine.
  • Patients were excluded if they had a history of seizure disorder or of having a seizure within 6 months of beginning the study, or suicidal ideation or severe depression within 3 months of beginning the study.
  • During Study 1, concomitant use of Zinbryta with the hepatotoxic drugs valproic acid, carbamazepine, lamotrigine, phenytoin, isoniazid, and propylthiouracil was not permitted except in patients already receiving the drugs at the time of study entry.
  • In clinical studies, serum chemistry was evaluated at baseline and monthly.
  • Hematology was evaluated at baseline, monthly for 6 months, and then every 3 months. Thyroid function was measured at baseline and every 6 months.

Table 2: Adverse Reactions in Adults with RMS with an Incidence at Least 2% More for Zinbryta 150 mg SQ Every 4 Weeks than AVONEX 30 mcg IM Once Weekly (Study 1)

Adverse Reaction Zinbryta 150 mg SQ Every 4 Weeks
N=919 %
AVONEX 30 mcg IM Once Weekly
N=922 %
Nasopharyngitis 25 21
Upper respiratory tract infection 1 17 14
Rash2 11 4
Influenza 9 6
Dermatitis 3 9 2
Oropharyngeal pain 8 4
Bronchitis 7 5
Eczema 4 5 2
Lymphadenopathy 5 <1
Tonsillitis 4 2
Acne 3 <1
1 includes upper respiratory tract infection and viral upper respiratory tract infection
2 includes erythematous rash, exfoliative rash, macular rash, maculopapular rash, papular rash, pruritic rash, rash, and vesicular rash
3 includes allergic dermatitis, atopic dermatitis, bullous dermatitis, dermatitis, exfoliative dermatitis, and seborrheic dermatitis
4 includes dyshidrotic eczema, eczema, and nummular eczema

Table 3: Adverse Reactions in Adults with RMS with an Incidence at Least 2% More for Zinbryta 150 mg SQ Every 4 Weeks than Placebo (Study 2)

Adverse Reaction Zinbryta 150 mg SQ Every 4 Weeks
N=208 %
Placebo
N=204 %
Upper respiratory tract infection 9 7
Depression1 7 2
Rash2 7 3
Pharyngitis 6 4
Increased ALT 5 2
Rhinitis 4 1
Anemia 3 <1
Pyrexia 3 <1
Increased AST 3 <1
Dermatitis 3 3 <1
1 includes depressed mood and depression
2 includes erythematous rash, exfoliative rash, macular rash, maculopapular rash, papular rash, pruritic rash, rash, and vesicular rash
3 includes allergic dermatitis, atopic dermatitis, bullous dermatitis, dermatitis, exfoliative dermatitis, and seborrheic dermatitis

Other clinically relevant adverse reactions observed at <2% difference included

Seizures
  • In Study 1, seizures occurred in 1% of Zinbryta-treated patients, compared with 0.3% of AVONEX-treated patients.
  • In Study 2, no seizures occurred in either treatment group.
Immune-Mediated Disorders
Breast Cancer
  • In controlled studies, 1 Zinbryta-treated woman developed breast cancer compared with none in the AVONEX-treated group.
  • Across all controlled and open-label clinical studies, 8 of 1485 (0.5%) Zinbryta-treated women developed breast cancer, and 1 of 751 (0.1%) Zinbryta-treated men developed breast cancer.
  • It is unclear whether this represents an incidence increase over background rate.

Immunogenicity

  • As with all therapeutic proteins, there is potential for immunogenicity.
  • In Study 1, patients were tested for anti-drug (daclizumab) antibodies at Week 4 and approximately every 3 months thereafter.
  • Anti-drug antibodies and neutralizing antibodies were observed in 19% (175/913) and 8% (71/913) of patients, respectively.
  • Anti-drug antibody responses were transient in 12% (110/913) of patients and persistent in 7% (65/913) of patients.
  • Anti-drug and neutralizing antibody responses predominantly occurred during the first year of treatment, and their frequency declined with continued Zinbryta treatment.
  • In patients with neutralizing antibodies, daclizumab clearance was increased on average by 19%.
  • There was no apparent correlation of anti-drug antibody or neutralizing antibody development to clinical response, adverse reactions, or pharmacodynamic profile of Zinbryta.
  • The detection of antibody formation is highly dependent on the sensitivity and specificity of the assay. Additionally, the observed incidence of antibody positivity in an assay may be influenced by several factors including
    • assay methodology,
    • 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.

What drugs interact with Zinbryta (daclizumab)?

Hepatotoxic Drugs

  • Caution should be used when using hepatotoxic drugs, including non-prescription products, concomitantly with Zinbryta.
  • Carefully consider the need for the use of herbal products or dietary supplements that can cause hepatotoxicity.

Treatment & Diagnosis

Medications & Supplements

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You are encouraged to report negative side effects of prescription drugs to the FDA. Visit the FDA MedWatch website or call 1-800-FDA-1088.

Medically Reviewed on 12/24/2020
References
FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.