Cosentyx® 150 mg solution for injection in pre-filled syringe
Cosentyx® 150 mg solution for injection in pre-filled pen
Each pre-filled syringe contains 150 mg secukinumab* in 1 ml.
Each pre-filled pen contains 150 mg secukinumab* in 1 ml.
*Secukinumab is a recombinant fully human monoclonal antibody selective for interleukin-17A. Secukinumab is of the IgG1/κ-class produced in Chinese Hamster Ovary (CHO) cells.
For the full list of excipients, see section 6.1.
Solution for injection in pre-filled syringe (injection)
Solution for injection in pre-filled pen (SensoReady pen)
The solution is clear and colourless to slightly yellow.
Plaque psoriasis
Cosentyx is indicated for the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy.
Psoriatic arthritis
Cosentyx, alone or in combination with methotrexate (MTX), is indicated for the treatment of active psoriatic arthritis in adult patients when the response to previous disease-modifying anti-rheumatic drug (DMARD) therapy has been inadequate (see section 5.1).
Ankylosing spondylitis
Cosentyx is indicated for the treatment of active ankylosing spondylitis in adults who have responded inadequately to conventional therapy.
Cosentyx is intended for use under the guidance and supervision of a physician experienced in the diagnosis and treatment of conditions for which Cosentyx is indicated.
Posology
Plaque psoriasis
The recommended dose is 300 mg of secukinumab by subcutaneous injection with initial dosing at Weeks 0, 1, 2 and 3, followed by monthly maintenance dosing starting at Week 4. Each 300 mg dose is given as two subcutaneous injections of 150 mg.
Psoriatic arthritis
For patients with concomitant moderate to severe plaque psoriasis or who are anti-TNFα inadequate responders (IR), the recommended dose is 300 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2 and 3, followed by monthly maintenance dosing starting at Week 4. Each 300 mg dose is given as two subcutaneous injections of 150 mg.
For other patients, the recommended dose is 150 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2 and 3, followed by monthly maintenance dosing starting at Week 4.
Ankylosing spondylitis
The recommended dose is 150 mg by subcutaneous injection with initial dosing at Weeks 0, 1, 2 and 3, followed by monthly maintenance dosing starting at Week 4.
For all of the above indications, available data suggest that a clinical response is usually achieved within 16 weeks of treatment. Consideration should be given to discontinuing treatment in patients who have shown no response by 16 weeks of treatment. Some patients with an initial partial response may subsequently improve with continued treatment beyond 16 weeks.
Special populations
Elderly patients (aged 65 years and over)
No dose adjustment is required (see section 5.2).
Renal impairment / hepatic impairment
Cosentyx has not been studied in these patient populations. No dose recommendations can be made.
Paediatric population
The safety and efficacy of Cosentyx in children below the age of 18 years have not yet been established. No data are available.
Method of administration
Cosentyx is to be administered by subcutaneous injection. If possible, areas of the skin that show psoriasis should be avoided as injection sites.
After proper training in subcutaneous injection technique, patients may self-inject Cosentyx if a physician determines that this is appropriate. However, the physician should ensure appropriate follow-up of patients. Patients should be instructed to inject the full amount of Cosentyx according to the instructions provided in the package leaflet. Comprehensive instructions for administration are given in the package leaflet.
Severe hypersensitivity reactions to the active substance or to any of the excipients listed in section 6.1.
Clinically important, active infection (e.g. active tuberculosis; see section 4.4).
Infections
Cosentyx has the potential to increase the risk of infections. In clinical studies, infections have been observed in patients receiving Cosentyx (see section 4.8). Most of these were mild or moderate upper respiratory tract infections such as nasopharyngitis and did not require treatment discontinuation.
Related to the mechanism of action of Cosentyx, non-serious mucocutaneous candida infections were more frequently reported for secukinumab than placebo in the psoriasis clinical studies (3.55 per 100 patient years for secukinumab 300 mg versus 1.00 per 100 patient years for placebo) (see section 4.8).
Caution should be exercised when considering the use of Cosentyx 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 Cosentyx should not be administered until the infection resolves.
No increased susceptibility to tuberculosis was reported from clinical studies. However, Cosentyx should not be given to patients with active tuberculosis. Anti-tuberculosis therapy should be considered prior to initiation of Cosentyx in patients with latent tuberculosis.
Crohn's disease
Caution should be exercised when prescribing Cosentyx to patients with Crohn's disease as exacerbations of Crohn's disease, in some cases serious, were observed in clinical studies in both Cosentyx and placebo groups. Patients who are treated with Cosentyx and have Crohn's disease should be followed closely.
Hypersensitivity reactions
In clinical studies, rare cases of anaphylactic reactions have been observed in patients receiving Cosentyx. If an anaphylactic or other serious allergic reactions occur, administration of Cosentyx should be discontinued immediately and appropriate therapy initiated.
Latex-sensitive individuals
Cosentyx 150 mg solution for injection in pre-filled syringe
The removable needle cap of the Cosentyx pre-filled syringe contains a derivative of natural rubber latex. No natural rubber latex has to date been detected in the removable needle cap. Nevertheless, the use of Cosentyx pre-filled syringes in latex-sensitive individuals has not been studied and there is therefore a potential risk of hypersensitivity reactions which cannot be completely ruled out.
Cosentyx 150 mg solution for injection in pre-filled pen
The removable cap of the Cosentyx pre-filled pen contains a derivative of natural rubber latex. No natural rubber latex has to date been detected in the removable cap. Nevertheless, the use of Cosentyx pre-filled pens in latex-sensitive individuals has not been studied and there is therefore a potential risk for hypersensitivity reactions which cannot be completely ruled out.
Vaccinations
Live vaccines should not be given concurrently with Cosentyx.
Patients receiving Cosentyx may receive concurrent inactivated or non-live vaccinations. In a study, after meningococcal and inactivated influenza vaccinations, a similar proportion of healthy volunteers treated with 150 mg of secukinumab and those treated with placebo were able to mount an adequate immune response of at least a 4-fold increase in antibody titres to meningococcal and influenza vaccines. The data suggest that Cosentyx does not suppress the humoral immune response to the meningococcal or influenza vaccines.
Concomitant immunosuppressive therapy
In psoriasis studies, the safety and efficacy of Cosentyx in combination with immunosuppressants, including biologics, or phototherapy have not been eva luated (see also section 4.5).
Live vaccines should not be given concurrently with Cosentyx (see also section 4.4).
No interaction studies have been performed in humans. There is no direct evidence for the role of IL-17A in the expression of CYP450 enzymes. The formation of some CYP450 enzymes is suppressed by increased levels of cytokines during chronic inflammation. Thus, anti-inflammatory treatments, such as with the IL-17A inhibitor secukinumab, may result in normalisation of CYP450 levels with accompanying lower exposure of CYP450-metabolised co-medications. Therefore, a clinically relevant effect on CYP450 substrates with a narrow therapeutic index, where the dose is individually adjusted (e.g. warfarin) cannot be excluded. On initiation of secukinumab therapy in patients being treated with these types of medicinal products, therapeutic monitoring should be considered.
No interaction was seen when Cosentyx was administered concomitantly with methotrexate (MTX) and/or corticosteroids in arthritis studies (including in patients with psoriatic arthritis and ankylosing spondylitis).
Women of childbearing potential
Women of childbearing potential should use an effective method of contraception during treatment and for at least 20 weeks after treatment.
Pregnancy
There are no adequate data from the use of secukinumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development, parturition or postnatal development (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Cosentyx in pregnancy.
Breast-feeding
It is not known whether secukinumab is excreted in human milk. Immunoglobulins are excreted in human milk and it is not known if secukinumab is absorbed systemically after ingestion. Because of the potential for adverse reactions in nursing infants from secukinumab, a decision on whether to discontinue breast-feeding during treatment and up to 20 weeks after treatment or to discontinue therapy with Cosentyx must be made taking into account the benefit of breast-feeding to the child and the benefit of Cosentyx therapy to the woman.
Fertility
The effect of secukinumab on human fertility has not been eva luated. Animal studies do not indicate direct or indirect harmful effects with respect to fertility (see section 5.3).
Cosentyx has no or negligible influence on the ability to drive and use machines.
Summary of the safety profile
A total of 6,200 patients have been treated with Cosentyx in blinded and open-label clinical studies in various indications (plaque psoriasis, psoriatic arthritis, ankylosing spondylitis and other autoimmune conditions). Of these, 3,671 patients were exposed to Cosentyx for at least one year, representing 6,267 patient years of exposure.
Adverse reactions in plaque psoriasis
Four placebo-controlled phase III studies in plaque psoriasis were pooled to eva luate the safety of Cosentyx in comparison to placebo up to 12 weeks after treatment initiation. In total, 2,076 patients were eva luated (692 patients on 150 mg, 690 patients on 300 mg and 694 patients on placebo).
The most frequently reported adverse drug reactions (ADRs) were upper respiratory tract infections (most frequently nasopharyngitis, rhinitis). Most of the reactions were mild or moderate in severity.
Adverse reactions in psoriatic arthritis
Cosentyx was studied in two placebo-controlled psoriatic arthritis studies with 1,003 patients (703 patients on Cosentyx and 300 patients on placebo) for a total exposure of 1,061 patient-years of study exposure (median duration of exposure for secukinumab-treated patients: 456 days in PsA Study 1 and 245 days in PsA Study 2). The safety profile observed in patients with psoriatic arthritis treated with Cosentyx is consistent with the safety profile in psoriasis.
Adverse reactions in ankylosing spondylitis
Cosentyx was studied in two placebo-controlled ankylosing spondylitis studies with 590 patients (394 patients on Cosentyx and 196 patients on placebo) for a total of 755 patient-years of study exposure (median duration of exposure for secukinumab-treated patients: 469 days in AS Study 1 and 460 days in AS Study 2). The safety profile observed in patients with ankylosing spondylitis treated with Cosentyx is consistent with the safety profile in psoriasis.
Tabulated list of adverse reactions
ADRs from psoriasis, psoriatic arthritis and ankylosing spondylitis clinical studies (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 adverse drug 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); very rare (<1/10,000).
Table 1 List of adverse reactions in clinical studies1)
|
System Organ Class
|
Frequency
|
Adverse reaction
|
|
Infections and infestations
|
Very common
|
Upper respiratory tract infections
|
|
Common
|
Oral herpes
|
|
Uncommon
|
Oral candidiasis
|
|
Tinea pedis
|
|
Otitis externa
|
|
Blood and lymphatic system disorders
|
Uncommon
|
Neutropenia
|
|
Immune system disorders
|
Rare
|
Anaphylactic reactions
|
|
Eye disorders
|
Uncommon
|
Conjunctivitis
|
|
Respiratory, thoracic and mediastinal disorders
|
Common
|
Rhinorrhoea
|
|
Gastrointestinal disorders
|
Common
|
Diarrhoea
|
|
Skin and subcutaneous disorders
|
Uncommon
|
Urticaria
|
|
1) Placebo-controlled clinical studies (phase III) in plaque psoriasis, PsA and AS patients exposed to 300 mg, 150 mg, 75 mg or placebo up to 12 weeks (psoriasis) or 16 weeks (PsA and AS) treatment duration
|
Description of selected adverse reactions
Infections
In the placebo-controlled period of clinical studies in plaque psoriasis (a total of 1,382 patients treated with Cosentyx and 694 patients treated with place
