Brodalumab interacts in the following cases:
Live vaccines should not be given concurrently with brodalumab.
In patients with moderate to severe plaque psoriasis, a single subcutaneous dose of 210 mg brodalumab increased the exposure of midazolam, a CYP3A4/3A5 substrate by 24%. Based on the magnitude of change in exposure of midazolam, no dose adjustment of CYP3A4/3A5 substrates is necessary when administered concomitantly with brodalumab.
It is recommended that patients be brought up-to-date with all immunisations in accordance with local immunisation guidelines prior to initiation of treatment with brodalumab. Live vaccines should not be given concurrently with brodalumab. No data are available on the response to live vaccines or the risk of infection, or transmission of infection after the administration of live vaccines in patients receiving brodalumab.
Vaccination of infants with live vaccines following third trimester exposure to brodalumab should be discussed with a physician.
Suicidal ideation and behaviour, including completed suicide, have been reported in patients treated with brodalumab. The majority of patients with suicidal behaviour had a history of depression and/or suicidal ideation or behaviour. A causal association between treatment with brodalumab and increased risk of suicidal ideation and behaviour has not been established.
The risk and benefit of treatment with brodalumab should be carefully weighed for patients with a history of depression and/or suicidal ideation or behaviour, or for patients who develop such symptoms. Patients, caregivers, and families should be advised of the need to be alert for the emergence or worsening of depression, suicidal ideation, anxiety, or other mood changes, and they should contact their healthcare provider if such events occur. If a patient suffers from new or worsening symptoms of depression and/or suicidal ideation or behaviour is identified, it is recommended to discontinue treatment with brodalumab.
There are no or limited amount of data from the use of brodalumab in pregnant women.
Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity.
Human IgG2 is known to cross the placental barrier and brodalumab is a human IgG2, therefore, brodalumab has the potential to be transmitted from the mother to the developing foetus. As a precautionary measure, it is preferable to avoid the use of brodalumab in pregnancy.
As the metabolism of brodalumab is unknown in infants, benefit risk for exposure of the infant to live vaccines following third trimester exposure to brodalumab should be discussed with a physician.
It is unknown whether brodalumab is excreted in human milk. Brodalumab is a monoclonal antibody and is expected to be present in the first milk and at low levels afterwards.
A risk to the newborns/infants cannot be excluded.
A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from brodalumab therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Women of childbearing potential should use an effective method of contraception during treatment and for at least 12 weeks after treatment.
No data are available on the effect of brodalumab on human fertility. Animal studies did not show any effects on male and female reproductive organs and on sperm count, motility and morphology.
Brodalumab has no or negligible influence on the ability to drive and use machines.
The most commonly reported adverse reactions in all brodalumab-treated patients were arthralgia (4.6%), headache (4.3%), fatigue (2.6%), diarrhoea (2.2%), and oropharyngeal pain (2.1%).
Adverse reactions from clinical trials are listed by MedDRA system organ class (SOC). Within each SOC, the adverse reactions are ranked by frequency, with the most frequent reactions first. Within each frequency grouping adverse reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each adverse reaction is based on the following convention: 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) and very rare (<1/10,000).
List of adverse reactions in clinical trials:
Common: Influenza Tinea infections (including tinea pedis, tinea versicolor, tinea cruris)
Uncommon: Candida infections (including oral, genital, and oesophageal infections)
Common: Neutropenia
Common: Headache
Uncommon: Conjunctivitis
Common: Oropharyngeal pain
Common: Diarrhoea Nausea
Common: Arthralgia, Myalgia
Common: Fatigue, Injection site reactions (including injection site erythema, pain, pruritus, bruising, haemorrhage)
During the 12-week placebo-controlled trial period in plaque psoriasis, infections were reported in 25.4% of patients treated with brodalumab compared with 23.4% of patients treated with placebo. The majority of infections consisted of nasopharyngitis, upper respiratory tract infection, pharyngitis, urinary tract infections, bronchitis, and influenza, which did not necessitate treatment discontinuation. Serious infections occurred in 0.5% of patients treated with brodalumab and in 0.2% of patients treated with placebo. Higher rates of fungal infections, primarily non-serious skin and mucosal candida infections, were observed in brodalumab patients compared to placebo patients, 1.8% vs 0.9%, respectively. One serious case of cryptococcal meningitis and one serious case of coccidioidies infection were observed in clinical trials.
Through Week 52, the exposure-adjusted event rates (per 100 patient-years) for infections were 114.6 for patients treated with brodalumab and 118.1 for patients treated with ustekinumab. The exposureadjusted event rates (per 100 patient-years) for serious infections were 1.3 for patients treated with brodalumab and 1.0 for patients treated with ustekinumab.
During the 12-week placebo-controlled period of clinical trials, neutropenia was reported in 0.8% of patients treated with brodalumab compared with 0.5% of patients treated with placebo. Most adverse reactions of brodalumab-associated neutropenia observed were mild, transient and reversible.
Neutropenia Grade 3 and 4 were reported in 0.4% of patients receiving brodalumab compared to 0.2% of patients who received ustekinumab and none in patients receiving placebo. No serious infections were associated with neutropenia.
Antibodies to brodalumab developed in 2.7% (122/4461) of patients treated with brodalumab for up to 52 weeks in psoriasis clinical trials (0.3% of these patients had anti-brodalumab antibodies at baseline). Of these patients, none had neutralising antibodies.
No evidence of altered pharmacokinetic profile, clinical response, or safety profile was associated with anti-brodalumab antibody development.
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