Source: European Medicines Agency (EU) Revision Year: 2019 Publisher: Eli Lilly Nederland B.V., Papendorpseweg 83, 3528 BJ Utrecht, The Netherlands
Serious hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Clinically important active infections (e.g. active tuberculosis, see section 4.4).
Treatment with Taltz is associated with an increased rate of infections such as upper respiratory tract infection, oral candidiasis, conjunctivitis, and tinea infections (see section 4.8).
Taltz should be used with caution in patients with clinically important chronic infection. If such an infection develops, monitor carefully and discontinue Taltz if the patient is not responding to standard therapy or the infection becomes serious. Taltz should not be resumed until the infection resolves.
Taltz must not be given to patients with active tuberculosis (TB). Consider anti-TB therapy prior to initiation of Taltz in patients with latent TB.
Serious hypersensitivity reactions, including some cases of anaphylaxis, angioedema, urticaria and, rarely, late (10-14 days following injection) serious hypersensitivity reactions including widespread urticaria, dyspnea and high antibody titres have been reported. If a serious hypersensitivity reaction occurs, administration of Taltz should be discontinued immediately and appropriate therapy initiated.
Cases of new or exacerbations of Crohn’s disease and ulcerative colitis have been reported. Caution should be exercised when prescribing Taltz to patients with inflammatory bowel disease, including Crohn’s disease and ulcerative colitis, and patients should be monitored closely.
Taltz should not be used with live vaccines. No data are available on the response to live vaccines; there are insufficient data on response to inactive vaccines (see section 5.1).
This medicinal product contains less than 1 mmol sodium (23 mg) per 80 mg dose, i.e., essentially “sodium-free”.
In plaque psoriasis studies, the safety of Taltz in combination with other immunomodulatory agents or phototherapy has not been evaluated.
Results from a drug-drug interaction study in patients with moderate-to-severe psoriasis determined that 12 weeks of administration of ixekizumab with drugs metabolized by CYP3A4 (i.e., midazolam), CYP2C9 (i.e., warfarin), CYP2C19 (i.e., omeprazole), CYP1A2 (i.e., caffeine) or CYP2D6 (i.e., dextromethorphan) does not have a clinically significant impact on the pharmacokinetics of these drugs.
No interaction was seen when Taltz was administered concomitantly with methotrexate (MTX) and/or corticosteroids in patients with psoriatic arthritis.
Women of childbearing potential should use an effective method of contraception during treatment and for at least 10 weeks after treatment.
There is a limited amount of data from the use of ixekizumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development, parturition or post-natal development (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Taltz during pregnancy.
It is not known whether ixekizumab is excreted in human milk or absorbed systemically after ingestion. However, ixekizumab is excreted at low levels in the milk of cynomolgus monkeys. A decision should be made whether to discontinue breast-feeding or to discontinue Taltz taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.
The effect of ixekizumab on human fertility has not been evaluated. Animal studies do not indicate direct or indirect harmful effects with respect to fertility (see section 5.3).
Taltz has no or negligible influence on the ability to drive and use machines.
The most frequently reported adverse drug reactions (ADRs) were injection site reactions and upper respiratory tract infections (most frequently nasopharyngitis).
ADRs from clinical studies and postmarketing reports (Table 1) are listed by MedDRA system organ class. Within each system organ class, the ADRs are ranked by frequency, with the most frequent reactions first. Within each frequency grouping, adverse drug reactions are presented in order of decreasing seriousness. In addition, the corresponding frequency category for each ADR 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); very rare (<1/10,000).
A total of 7,339 patients have been treated with Taltz in blinded and open-label clinical studies in plaque psoriasis, psoriatic arthritis, and other autoimmune conditions. Of these, 4,500 patients were exposed to Taltz for at least one year, cumulatively representing 13,645.6 patient years of exposure.
In plaque psoriasis, three placebo-controlled phase III studies were integrated to evaluate the safety of Taltz in comparison to placebo up to 12 weeks after treatment initiation. A total of 3,119 patients were evaluated (1,161 patients on 80 mg every 4 weeks (Q4W), 1,167 patients on 80 mg every 2 weeks (Q2W) and 791 patients on placebo).
In psoriatic arthritis, two placebo-controlled phase III studies were integrated to evaluate the safety of Taltz in comparison to placebo up to 24 weeks after treatment initiation. A total of 678 patients were evaluated (229 patients on 80 mg every 4 weeks (Q4W), 225 patients on 80 mg every 2 weeks (Q2W) and 224 patients on placebo). The safety profile observed in patients with psoriatic arthritis treated with Taltz is consistent with the safety profile in plaque psoriasis with the exception of the frequencies of the adverse reactions of influenza and conjunctivitis which were common in patients with psoriatic arthritis.
Table 1. List of adverse reactions in clinical studiesa and postmarketing reports:
Very Common: Upper respiratory tract infectionb
Common: Tinea infection, Herpes simplex (mucocutaneous)c
Uncommon: Influenzai, Rhinitis, Oral candidiasisd, Conjunctivitisi, Cellulitise
Uncommon: Neutropeniag, Thrombocytopeniag
Uncommon: Angioedema
Rare: Anaphylaxish
Common: Oropharyngeal pain
Common: Nausea
Uncommon: Urticaria, Rash, Eczema,
Very common: Injection site reactionsf
a Placebo-controlled clinical studies (phase III) in moderate to severe plaque psoriasis patients exposed to ixekizumab 80 mg Q2W, ixekizumab 80 mg Q4W or placebo for up to 12 weeks of treatment duration, or in active psoriatic arthritis patients exposed to ixekizumab 80 mg Q2W, ixekizumab 80 mg Q4W or placebo for up to 24 weeks of treatment duration.
b Upper respiratory tract infection includes nasopharyngitis and upper respiratory tract infection.
c Herpes simplex (mucocutaneous) is defined as events with the preferred terms Oral herpes, Herpes simplex, Genital herpes, Herpes dermatitis, and Genital herpes simplex.
d Oral candidiasis defined as events with the preferred terms oral candidiasis and oral fungal infection .
e Cellulitis includes staphylococcal and external ear cellulitis, and erysipelas.
f In the plaque psoriasis studies, injection site reactions were more common in subjects with a body weight <60 kg compared with the group with a body weight ≥60 kg (25% vs. 14% for the combined Q2W and Q4W groups). In the psoriatic arthritis studies, injection site reactions were more common in subjects with a body weight <100 kg compared with the group with a body weight ≥100 kg (24% vs. 13% for the combined Q2W and Q4W groups). The increased frequency of injection site reactions in the combined Q2W and Q4W groups did not result in an increase in discontinuations in either the plaque psoriasis or the psoriatic arthritis studies.
g Based on reported adverse events.
h Based on postmarketing reports.
i Adverse drug reactions in patients treated with ixekizumab in the plaque psoriasis and psoriatic arthritis clinical trials were similar with the exception of the frequencies of influenza (common) and conjunctivitis (common) in the psoriatic arthritis clinical trials.
(Based on adverse reactions data from 4,204 patients with moderate to severe plaque psoriasis [4,729.7 patient years] and 1,117 patients with active psoriatic arthritis [1,050.6 patient years] who have received at least 1 dose of ixekizumab.)
The most frequent injection site reactions observed were erythema and pain. These reactions were predominantly mild to moderate in severity and did not lead to discontinuation of Taltz.
In the placebo-controlled period of the phase III clinical studies in plaque psoriasis, infections were reported in 27.2% of patients treated with Taltz for up to 12 weeks compared with 22.9% of patients treated with placebo.
The majority of infections were non-serious and mild to moderate in severity, most of which did not necessitate treatment discontinuation. Serious infections occurred in 13 (0.6%) of patients treated with Taltz and in 3 (0.4%) of patients treated with placebo (see section 4.4). Over the entire treatment period infections were reported in 52.8% of patients treated with Taltz (46.9 per 100 patient years). Serious infections were reported in 1.6% of patients treated with Taltz (1.5 per 100 patient years).
Infection rates observed in psoriatic arthritis clinical studies were similar to those observed in the plaque psoriasis studies with the exception of the frequencies of the adverse reactions of influenza and conjunctivitis which were common in patients with psoriatic arthritis.
In plaque psoriasis studies, 9% of patients receiving Taltz developed neutropenia. In most cases, the blood neutrophil count was ≥1,000 cells/mm³. Such levels of neutropenia may persist, fluctuate or be transient. 0.1% of patients receiving Taltz developed a neutrophil count <1000 cells/mm³. In general, neutropenia did not require discontinuation of Taltz. 3% of patients exposed to Taltz had a shift from a normal baseline platelet value to <150,000 platelet cells/mm³ to ≥75,000 cells/mm³. Thrombocytopenia may persist, fluctuate or be transient.
The frequency of neutropenia and thrombocytopenia in psoriatic arthritis clinical studies is similar to that observed in the plaque psoriasis studies.
Approximately 9–17% of plaque psoriasis patients treated with Taltz at the recommended dosing regimen developed anti-drug antibodies, the majority of which were low titres and not associated with reduced clinical response up to 60 weeks of treatment. However, approximately 1% of patients treated with Taltz had confirmed neutralising antibodies associated with low drug concentrations and reduced clinical response.
In psoriatic arthritis patients treated with Taltz at the recommended dosing regimen up to 52 weeks, approximately 11% developed anti-drug antibodies, the majority of which were low titre, and approximately 8% had confirmed neutralising antibodies. No apparent association between the presence of neutralising antibodies and impact on drug concentration or efficacy was observed.
An association between immunogenicity and treatment emergent adverse events has not been clearly established.
is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
Not applicable.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
