cidal behaviour had a history of depression and/or suicidal ideation or behaviour. A causal association between treatment with Kyntheum and increased risk of suicidal ideation and behaviour has not been established.
The risk and benefit of treatment with Kyntheum 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 Kyntheum.
Infections
Kyntheum may increase the risk of infections.
During the 12-week placebo-controlled clinical trial period in patients with psoriasis, serious infections were observed in 0.5% of patients receiving Kyntheum (see section 4.8).
Caution should be exercised when considering the use of Kyntheum in patients with a chronic infection or a history of recurrent infection. Patients should be instructed to seek medical advice if signs or symptoms suggestive of an infection occur. If a patient develops a serious infection, the patient should be closely monitored and Kyntheum should not be administered until the infection resolves.
No cases of active tuberculosis were reported from clinical trials. However, Kyntheum should not be given to patients with active tuberculosis. Anti-tuberculosis therapy should be considered prior to initiation of Kyntheum in patients with latent tuberculosis.
Reduced absolute neutrophil count
During the 12-week placebo-controlled clinical trial period in patients with psoriasis, a decrease in absolute neutrophil count (ANC) was observed in 5.6% of patients receiving Kyntheum, which was generally transient and reversible. Grade 3 and 4 has been observed occasionally. None of the Grade 3 or 4 ANC decreases in the psoriasis patients were associated with a serious infection (see also section 4.8).
Vaccinations
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 Kyntheum. Live vaccines should not be given concurrently with Kyntheum (see section 4.5). 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 Kyntheum.
Vaccination of infants
Vaccination of infants with live vaccines following third trimester exposure to Kyntheum should be discussed with a physician (see also section 4.6).
Concomitant immunosuppressive therapy
The safety and efficacy of Kyntheum in combination with immunosuppressants, including biologics, or phototherapy have not been eva luated.
4.5 Interaction with other medicinal products and other forms of interaction
Live vaccines should not be given concurrently with Kyntheum (see section 4.4).
The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g. IL-1, IL-6, IL-10, TNFα, IFN) during chronic inflammation. Although a role for interleukin (IL)-17A and IL-17RA in the regulation of CYP450 enzymes has not been reported, the effect of brodalumab on CYP3A4/3A5 activity was eva luated in a di |
