Daclizumab interacts in the following cases:
The safety of immunisation with live viral vaccines during treatment with daclizumab has not been studied. Vaccination with live vaccines is not advised during treatment and up to 4 months after discontinuation.
In a clinical study, patients (n=90) on long-term treatment with daclizumab mounted appropriate immune responses to an inactivated trivalent seasonal influenza vaccine. The magnitude of the immune response to the seasonal influenza vaccine, and proportion of patients with seroconversion and seroprotection were consistent with those observed in healthy volunteer populations. Patients on daclizumab may receive non-live vaccines.
Cases of hepatic injury have occurred in patients taking daclizumab with other hepatotoxic drugs, although the role of these medicinal products is uncertain. Caution is recommended when administering medicinal products of known hepatotoxic potential including non-prescription products and herbal supplements concomitantly with daclizumab.
Daclizumab should be administered with caution to patients with previous or current depressive disorders. Patients treated with daclizumab should be advised to report any symptoms of new or worsening depression, and/or suicidal ideation immediately to the prescribing physician. If a patient develops severe depression, and/or suicidal ideation, discontinuation of daclizumab should be considered.
Treatment initiation is not recommended in patients with history of concurrent autoimmune conditions other than multiple sclerosis.
There are limited data from the use of daclizumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reprotoxicity. Daclizumab should be used during pregnancy only if the potential benefit justifies the potential risk to the foetus.
Available toxicology data in lactating cynomolgus monkeys have shown excretion of daclizumab beta in milk. It is not known whether daclizumab is secreted in human milk. Although human IgG is secreted into human milk, published data suggest that antibodies in breast milk do not enter the neonatal and infant circulations in substantial amounts. A risk to newborns/infants cannot be excluded.
If a woman wishes to breast-feed during treatment with daclizumab, the benefit of breast-feeding to the child and of therapy to the woman should be considered.
No impact on male or female fertility as assessed by fertility indices was detected in animal studies. There are no data on the effects of daclizumab on human fertility.
Daclizumab has no or negligible influence on the ability to drive and use machines.
In the placebo-controlled study (the SELECT study), 417 patients received daclizumab (150 mg, n=208; 300 mg, n=209; every 4 weeks) for up to 1 year. In the active-controlled study (the DECIDE study), 919 patients received daclizumab (150 mg, every 4 weeks) and 922 patients received interferon beta-1a intramuscular, (30 microgram weekly) for a minimum of 2 years and up to 3 years.
The most commonly reported adverse reactions leading to discontinuation in patients treated with daclizumab were hepatic reactions, including elevations of serum transaminases (5%), and cutaneous reactions (4%).
The most common adverse reactions reported for daclizumab were rash, increased alanine aminotransferase (ALT), depression, nasopharyngitis, upper respiratory tract infection, influenza, oropharyngeal pain, and lymphadenopathy.
The adverse reactions are presented as MedDRA preferred terms under the MedDRA System Order Class by frequency and incidence. Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. The incidence of the adverse reactions is expressed according to the following categories: Very common (≥1/10), Common (≥1/100 to <1/10), Uncommon (≥1/1,000 to <1/100), Rare (≥1/10, 000 to <1/1,000), Very rare (<1/10,000), Not known (cannot be estimated from the available data).
Adverse reactions reported for daclizumab 150mg:
Very Common: Upper respiratory tract infection†, Nasopharyngitis†
Common: Pneumonia, Respiratory tract infection, Bronchitis, Viral infection, Influenza†, Laryngitis, Tonsillitis†, Pharyngitis, Folliculitis, Rhinitis*
Common: Lymphadenopathy†, Lymphadenitis, Anaemia*
Uncommon: Autoimmune haemolytic anaemia
Uncommon: Sarcoidosis
Common: Depression*
Common: Oropharyngeal pain†
Common: Diarrhoea, Colitis
Common: Dermatitis, Dermatitis allergic, Eczema†, Psoriasis, Seborrhoeic dermatitis†, Skin exfoliation, Rash*†, Rash maculopapular, Acne†, Erythema, Pruritus, Dry skin
Uncommon: Exfoliative rash, Toxic skin eruption, Eczema nummular
Common: Pyrexia*
Very common: Transaminases increased
Uncommon: Autoimmune hepatitis
Not known: Fulminant hepatitis
Very common: Liver function test abnormal
Common: Lymphocyte count decreased
* Observed with a ≥2% higher incidence than placebo
† Observed with a ≥2% higher incidence than interferon beta-1a (intramuscular)
Serious hepatic injury, including fatal cases of autoimmune hepatitis and fulminant liver failure have occurred in patients treated with daclizumab. Serious reactions, including autoimmune hepatitis, hepatitis and jaundice, were observed in 1.7% of patients in clinical trials.
In clinical studies, serum transaminase elevations occurred at any time during treatment and up to 6 months after the last dose of daclizumab. Most patients had mild elevations that were below or up to 3 x ULN and resolved spontaneously. In clinical trials, an increased incidence of elevations of ALT or AST was reported more frequently in daclizumab-treated patients compared to placebo or interferon beta1a (intramuscular). The incidence of discontinuation due to medicine related hepatic disorders was 5% in daclizumab-treated patients and 4% in interferon beta-1a (intramuscular).
Cumulative incidences of peak ALT or AST increase (based on laboratory data) observed in clinical trials:
| Daclizumab 150 mg (N=1943) | Interferon beta-1a (N=922) | Placebo (N=204) | |
|---|---|---|---|
| Total exposure (subject-years) | 7011 | 1884 | 210 |
| ≥3 x ULN | 13.6% | 8.5% | 3.4% |
| >5 x ULN | 9.0% | 3.4% | 0.5% |
| >10 x ULN | 4.3% | 1.3% | 0.0% |
| >20 x ULN | 1.4% | 0.4% | 0.0% |
| AST ή ALT ≥3 x ULN AND total bilirubin ≥ x 2 ULN | 0.77% | 0.1% | 0.5% |
In clinical studies daclizumab increased the incidence of skin reactions [18% vs 13% (placebo); 37% vs 19% (interferon beta-1a (intramuscular))] and serious skin reactions [<1% vs 0% (placebo); 2% vs <1% (interferon beta-1a (intramuscular))] compared to placebo and interferon beta-1a (intramuscular).
The most common skin reactions were rash, dermatitis, and eczema. The majority of patients had skin reactions that were mild or moderate in severity. Discontinuation due to skin reactions was 4% in daclizumab-treated patients.
In clinical studies, daclizumab increased the incidence of depression [5% vs 1% (placebo); 8% vs 6% (interferon beta-1a (intramuscular))]; the incidence of serious reactions of depression was <1% with daclizumab.
In clinical studies, daclizumab increased the incidence of infections [50% vs 44% (placebo) and 65% vs 57% (interferon beta-1a (intramuscular))] and serious infections [3% vs 0% (placebo); 4% vs 2% (interferon beta-1a (intramuscular))] compared to placebo and interferon beta-1a (intramuscular). The most common types of infections were upper respiratory tract infections and viral infections. The median duration was similar between the treatment groups. The rate of infections and serious infections did not increase over time. The majority of patients with infections continued on treatment with daclizumab. Discontinuation of daclizumab due to infections was <1%.
Autoimmune haemolytic anaemia was reported in <1% of patients treated with daclizumab in clinical studies.
An increased incidence of serious colitis (<1%) was reported in patients treated with daclizumab in clinical studies.
In clinical studies, daclizumab increased the incidence of lymphadenopathy, with onset occurring throughout the treatment period. Discontinuation due to lymphadenopathy was <1% in daclizumab-treated patients. The majority of patients with lymphadenopathy continued on treatment with daclizumab, and the majority of cases resolved within 3 months.
In the DECIDE study, patients were tested for anti-drug (daclizumab beta) antibodies at week 4 and approximately every 3 months thereafter. Treatment-emergent anti-drug antibodies and neutralising antibodies were observed in 19% (175/913) and 8% (71/913) of study patients, respectively. The majority of the treatment-emergent anti-drug antibodies responses were transient (12% [110/913]) and the remaining minority (7% [65/913]) were persistent. Among the evaluable patients, the majority of treatment-emergent neutralising antibody responses were transient (6% [56 of 913]) and 2% of patients (15 of 913) had persistent responses. Treatment-emergent anti-drug antibodies and neutralising antibodies responses predominantly occurred during the first year of treatment and their frequency declined with continued daclizumab treatment.
In patients with neutralising antibodies, daclizumab beta clearance was increased on average by 19%. There was no apparent correlation of anti-drug antibodies or neutralising antibodies development to clinical response, adverse reactions, or pharmacodynamic profile of daclizumab beta.
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