sease-drug-drug interaction study.
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 Kyntheum.
4.6 Fertility, pregnancy and lactation
Women of childbearing potential
Women of childbearing potential should use an effective method of contraception during treatment and for at least 12 weeks after treatment.
Pregnancy
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 (see section 5.3).
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 Kyntheum 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 Kyntheum should be discussed with a physician.
Breast-feeding
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 Kyntheum therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
Fertility
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 (see section 5.3).
4.7 Effects on ability to drive and use machines
Kyntheum has no or negligible influence on the ability to drive and use machines.
4.8 Undesirable effects
Summary of the safety profile
The most commonly reported adverse reactions in all Kyntheum-treated patients were arthralgia (4.6%), headache (4.3%), fatigue (2.6%), diarrhoea (2.2%), and oropharyngeal pain (2.1%).
Tabulated list of adverse reactions
Adverse reactions from clinical trials (Table 1) 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).
Table 1: List of adverse reactions in clinical trials
System Organ Class
Frequency
Adverse Reaction
Infections and infestations
Common
Influenza
Tinea infections (including tinea pedis, tinea versicolor, tinea cruris)
Uncommon
Candida infections (including oral, genital, and oesophageal infections)
Blood and lymphatic system disorders
Common
Neutropenia
Nervous system disorders
Common
Headache
Eye disorders
Uncommon
Conjunctivitis
Respiratory, thoracic and mediastinal disorders
Common
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