Enter drug's generic or brand name below. Results will appear here. Note: all drug related information obtained on this page is provided by RX List.
Using the RX LIST database:
(1) Enter the drug name in the search box below and hit ENTER
(2) The rx list web site will open here with the drug search completed. Next, scroll down the page to locate the link to the drug you are searching for and then click on the link.
Secukinumab is a recombinant human monoclonal IgG1/κ antibody that binds specifically to IL-17A. It is expressed in a recombinant Chinese Hamster Ovary (CHO) cell line. Secukinumab has a molecular mass of approximately 151 kDa; both heavy chains of secukinumab contain oligosaccharide chains.
COSENTYX injection is a sterile, preservative-free, clear to slightly opalescent, colorless to slightly yellow solution. COSENTYX is supplied in a single-use Sensoready pen with a 27-gauge fixed ½-inch needle, or a single-use prefilled syringe with a 27-gauge fixed ½-inch needle. The removable cap of the COSENTYX Sensoready pen or prefilled syringe contains natural rubber latex.
Each COSENTYX Sensoready pen or prefilled syringe contains 150 mg of secukinumab formulated in: L-histidine/histidine hydrochloride monohydrate (3.103 mg), L-methionine (0.746 mg), polysorbate 80 (0.2 mg), trehalose dihydrate (75.67 mg), and Sterile Water for Injection, USP, at pH of 5.8.
COSENTYX for injection is supplied as a sterile, preservative free, white to slightly yellow, lyophilized powder in single-use vials. Each COSENTYX vial contains 150 mg of secukinumab formulated in L-histidine/histidine hydrochloride monohydrate (4.656 mg), polysorbate 80 (0.6 mg), and sucrose (92.43 mg). Following reconstitution with 1 mL Sterile Water for Injection, USP, the resulting pH is approximately 5.8.
The following adverse reactions are discussed in greater detail elsewhere in the labeling:
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
Adverse Reactions in Clinical Trials of Subcutaneous COSENTYX
A total of 3,430 adult subjects with PsO were treated with COSENTYX in controlled and uncontrolled clinical trials. Of these, 1,641 subjects were treated with COSENTYX for at least 1 year.
Four placebo-controlled Phase 3 trials in PsO subjects (Trials PsO1, PsO2, PsO3, and PsO4) were pooled to evaluate the safety of COSENTYX in comparison to placebo up to 12 weeks after treatment initiation. In total, 2,077 subjects were evaluated (691 in the COSENTYX 300 mg group, 692 in the COSENTYX 150 mg group, and 694 in the placebo group). Subjects randomized to COSENTYX received 300 mg or 150 mg doses subcutaneously at Weeks 0, 1, 2, 3, and 4 followed by the same dose every 4 weeks [see Clinical Studies (14)].
Table 2 summarizes the adverse reactions that occurred at a rate of at least 1% and at a higher rate in the COSENTYX groups than the placebo group during the 12-week placebo-controlled period of these trials.
Table 2: Adverse Reactions Reported by Greater Than 1% of Adult Subjects With PsO (and at a Higher Rate in Subjects Treated with COSENTYX) Through Week 12 in Trials PsO1, PsO2, PsO3, and PsO4
| Adverse reactions | COSENTYX | Placebo (N = 694) n (%) |
|
| 300 mg (N = 691) n (%) |
150 mg (N = 692) n (%) |
||
| Nasopharyngitis | 79 (11.4) | 85 (12.3) | 60 (8.6) |
| Diarrhea | 28 (4.1) | 18 (2.6) | 10 (1.4) |
| Upper respiratory tract infection | 17 (2.5) | 22 (3.2) | 5 (0.7) |
| Rhinitis | 10 (1.4) | 10 (1.4) | 5 (0.7) |
| Oral herpes | 9 (1.3) | 1 (0.1) | 2 (0.3) |
| Pharyngitis | 8 (1.2) | 7 (1.0) | 0 (0) |
| Urticaria | 4 (0.6) | 8 (1.2) | 1 (0.1) |
| Rhinorrhea | 8 (1.2) | 2 (0.3) | 1 (0.1) |
Adverse reactions that occurred in subjects treated with COSENTYX at rates less than 1% in the placebo-controlled period of Trials PsO1, PsO2, PsO3, and PsO4 through Week 12 included: sinusitis, tinea pedis, conjunctivitis, tonsillitis, oral candidiasis, impetigo, otitis media, otitis externa, IBD, increased liver transaminases, and neutropenia.
Infections
In the placebo-controlled period of the clinical trials in PsO (a total of 1,382 subjects treated with COSENTYX and 694 subjects treated with placebo up to 12 weeks), infections were reported in 28.7% of subjects treated with COSENTYX compared with 18.9% of subjects treated with placebo.
Over the entire treatment period (a total of 3,430 PsO subjects treated with COSENTYX for up to 52 weeks for the majority of subjects), infections were reported in 47.5% of subjects treated with COSENTYX (0.9 per subject-year of follow-up) and serious infections were reported in 1.2% of subjects treated with COSENTYX (0.015 per subject-year of follow-up).
Phase 3 data showed an increasing trend for some types of infection with increasing serum secukinumab concentrations. Candida infections, herpes viral infections, staphylococcal skin infections, and infections requiring treatment increased as serum secukinumab concentration increased.
In the PsO open-label extension of Trials PsO1 and PsO2 (median follow-up of 3.9 years), representing 3,582 subjectyears of exposure, 74% of COSENTYX treated subjects reported infections (55 per 100 subject-years) and serious infections were reported in 4.5% of COSENTYX treated subjects (1.4 per 100 subject-years). Sepsis was reported in 5 COSENTYX treated subjects (0.2 per 100 subject-years).
Neutropenia was observed in controlled portion of clinical trials. Most cases of COSENTYX associated neutropenia were transient and reversible. No serious infections were associated with cases of neutropenia.
In the open-label extension of Trials PsO1 and PsO2, neutropenia (ANC < 1 x 109/L) was reported in 1% of COSENTYX treated subjects (0.3 per 100 subject-years). Some cases of serious infections were associated with neutropenia; however, the causal relationship was not established.
Inflammatory Bowel Disease
Cases of IBD, in some cases serious, were observed in subjects treated with COSENTYX in clinical trials. In the PsO program, with 3,430 subjects exposed to COSENTYX over the entire treatment period for up to 52 weeks (2,725 subjectyears), there were 3 cases (0.11 per 100 subject-years) of exacerbation of CD, 2 cases (0.08 per 100 subject-years) of exacerbation of UC, and 2 cases (0.08 per 100 subject-years) of new onset UC. There were no IBD cases in placebotreated subjects (N = 793; 176 subject-years) during the 12-week placebo-controlled period.
One case of exacerbation of Crohn’s disease in a subject treated with COSENTYX subject was reported in open-label portions of clinical trials in PsO.
The safety of COSENTYX was assessed in two Phase 3 trials in pediatric subjects with PsO.
The safety profile of COSENTYX reported in these trials was consistent with the safety profile reported in adult PsO trials.
Infections
One case of methicillin-resistant Staphylococcus aureus (MRSA) toxic shock syndrome (TSS) was reported in a COSENTYX treated pediatric subject during the placebo-controlled period.
In the pediatric safety pool, which includes all subjects who took at least one dose of COSENTYX during the treatment periods [198 subjects (287 subject-years)], 22 (11%) subjects reported ≥ Common Terminology Criteria for Adverse Events (CTCAE) Grade 2 neutropenia (≥ 1,000 to < 1,500 cells/mm3) with 57% of subjects followed for one year or more and 30% of subjects followed for two years or more. During the placebo-controlled period, which included a total of 80 pediatric subjects treated with COSENTYX and 41 subjects treated with placebo up to 12 weeks, ≥ CTCAE Grade 2 neutropenia was reported in 3 (4%) of the subjects treated with COSENTYX compared with no subjects treated with placebo. No serious infections were associated with cases of neutropenia.
COSENTYX was studied in two placebo-controlled PsA trials with 1,003 adult patients (703 patients on COSENTYX and 300 patients on placebo). Of the 703 patients who received COSENTYX, 299 patients received a subcutaneous loading dose of COSENTYX (PsA1) and 404 patients received an intravenous loading dose of secukinumab (PsA2) followed by COSENTYX administered by subcutaneous injection every four weeks. During the 16-week placebo-controlled period of the trials in patients with PsA, the overall proportion of patients with adverse events was similar in the secukinumab and placebo-treatment groups (59% and 58%, respectively). The adverse events that occurred at a proportion of at least 2% and at a higher proportion in the COSENTYX groups than the placebo groups during the 16-week placebo-controlled period were nasopharyngitis, upper respiratory tract infection, headache, nausea, and hypercholesterolemia. The safety profile observed in adult patients with PsA treated with COSENTYX is consistent with the safety profile in the PsO trials in adults.
Similar to the clinical trials in patients with PsO, there was an increased proportion of patients with infections in the COSENTYX groups (29%) compared to placebo group (26%).
There were cases of CD and UC in the secukinumab group that included patients who experienced either exacerbations or the development of new disease. There were three cases of IBD, of which two patients received secukinumab and one received placebo.
COSENTYX was studied in two placebo-controlled AS trials with 590 adult patients (394 patients on COSENTYX and 196 patients on placebo). Of the 394 patients who received COSENTYX, 145 patients received a subcutaneous load of COSENTYX (study AS1), and 249 received an intravenous loading dose of secukinumab (study AS2) followed by COSENTYX administered by subcutaneous injection every four weeks. During the 16-week placebo-controlled period of the trials in patients with AS, the overall proportion of patients with adverse events was higher in the secukinumab groups than the placebo-treatment groups (66% and 59%, respectively). The adverse events that occurred at a proportion of at least 2% and at a higher proportion in the COSENTYX groups than the placebo groups during the 16-week placebocontrolled period were nasopharyngitis, nausea, and upper respiratory tract infection. The safety profile observed in patients with AS treated with COSENTYX is consistent with the safety profile in PsO clinical trials. In a third controlled trial of AS (study AS3), the safety profile of the 300 mg dose of COSENTYX was consistent with the safety profile of the 150 mg dose of COSENTYX.
Similar to clinical trials in patients with PsO, there was an increased proportion of patients with infections in the COSENTYX groups (31%) compared to the placebo group (18%).
In the original AS program, with 571 patients exposed to COSENTYX, there were 8 cases of IBD during the entire treatment period [5 cases of Crohn’s (0.7 per 100 patient-years) and 3 cases of UC (0.4 per 100 patient-years)]. During the placebo-controlled 16-week period, there were 2 Crohn’s disease exacerbations and 1 new onset UC case that was a serious adverse event in patients treated with COSENTYX compared to none of the patients treated with placebo. During the remainder of the trial when all patients received COSENTYX, 1 patient developed Crohn’s disease, 2 patients had Crohn’s exacerbations, 1 patient developed UC, and 1 patient had an UC exacerbation.
COSENTYX was studied in one randomized, double-blind, placebo-controlled nr-axSpA trial with 555 adult patients (185 patients received a loading COSENTYX dose, 184 patients did not receive a loading COSENTYX dose, and 186 patients received placebo). The safety profile for patients with nr-axSpA treated with COSENTYX was overall similar to the safety profile seen in patients with AS and other previous experience with COSENTYX. Patients in nr-axSpA1 trial who received the loading dosing regimen compared to those without the loading regimen, had higher incidence of infections and infestations (92 per 100 patient-years versus 72 per 100 patient-years), including nasopharyngitis, upper respiratory tract infection and urinary tract infection, and gastrointestinal disorders (27 per 100 patient-years versus 22 per 100 patient-years), including gastritis, lower abdominal pain, colitis, diarrhea, and hematochezia.
COSENTYX was studied in one double-blind, placebo-controlled, event-driven, randomized trial in 86 pediatric patients aged 2 to less than 18 years old with JPsA and ERA. The safety profile reported in this trial was consistent with the safety profile of secukinumab.
COSENTYX was studied in two 52-week, randomized, double-blind, placebo-controlled HS trials with 1,084 adult subjects (361 subjects received COSENTYX 300 mg every 2 weeks, 360 subjects received COSENTYX 300 mg every 4 weeks, and 363 subjects received placebo) with a total of 901 subject-years of COSENTYX exposure (the median duration of exposure for subjects treated with COSENTYX was 360 days). The safety profile of COSENTYX observed in these HS trials was consistent with the known safety profile of COSENTYX observed in the PsO trials.
Infections
During the 16-week placebo-controlled period, subjects who received COSENTYX 300 mg every 2 weeks had the highest incidence of fungal infections (5.3%), compared to subjects who received COSENTYX 300 mg every 4 weeks (4.2%) and subjects who received placebo (2.8%). With longer exposure, the rate of fungal infections remained higher for subjects who received COSENTYX 300 mg every 2 weeks (14.7/100 subject-years) compared to subjects who received COSENTYX 300 mg every 4 weeks (10.1/100 subject-years). The majority of the cases were reported as non-serious, non-severe, and resolved with anti-fungal treatment.
Inflammatory Bowel Disease
In the open-labeled portion of HS clinical trials, five (0.7%) IBD adverse reactions were reported, all of which were serious and led to withdrawal of trial drug, and occurred only in subjects treated with COSENTYX 300 mg every 2 weeks. There were no IBD cases in subjects treated with COSENTYX 300 mg every 4 weeks.
Adverse Reactions of Intravenous COSENTYX
The safety of intravenous COSENTYX is based on the pharmacokinetic exposure and extrapolation of the established safety of subcutaneous COSENTYX in PsA, AS and nr-axSpA patients [see Clinical Pharmacology (12.3)].
The following adverse reactions have been reported during post-approval use of COSENTYX. Because they are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Immune system disorders: anaphylaxis, angioedema, systemic vasculitis
Skin and subcutaneous tissue disorders: eczematous eruptions (atopic dermatitis-like eruptions, dyshidrotic eczema, and erythroderma), cutaneous vasculitis, pyoderma gangrenosum
Infections: bacterial, viral, and fungal opportunistic infections, including esophageal candidiasis, tracheobronchial candidiasis, cutaneous aspergillosis, cytomegalovirus gastroenteritis/colitis, herpes simplex encephalitis, herpes simplex keratitis, Pneumocystis jiroveci pneumonia, Hepatitis B virus reactivation, histoplasmosis, toxoplasmosis
Increased concentrations of cytokines (e.g., IL-17) during chronic inflammation associated with certain diseases including PsO, PsA, AS, nr-axSpA, ERA, and HS may suppress the formation of CYP enzymes.
Upon initiation or discontinuation of COSENTYX in patients who are receiving concomitant CYP450 substrates, particularly those where minimal decreases in the concentration may reduce CYP substrate effectiveness or minimal increases in the concentration may increase CYP substrate adverse reactions, consider monitoring for therapeutic effect or concentration of the CYP substrate and consider dosage adjustment of the CYP substrate as needed [see Clinical Pharmacology (12.3)].
Included as part of the PRECAUTIONS section.
COSENTYX may increase the risk of infections. In clinical trials, a higher rate of infections was observed in COSENTYX treated subjects compared to placebo-treated subjects. In placebo-controlled clinical trials in subjects with moderate to severe PsO, higher rates of common infections, such as nasopharyngitis (11.4% versus 8.6%), upper respiratory tract infection (2.5% versus 0.7%) and mucocutaneous infections with candida (1.2% versus 0.3%) were observed in subjects treated with COSENTYX compared to placebo-treated subjects. A similar increase in risk of infection in subjects treated with COSENTYX was seen in placebo-controlled trials in subjects with PsA, AS and nraxSpA. The incidence of some types of infections, including fungal infections, appeared to be dose-dependent in clinical trials [see Adverse Reactions (6.1)].
In the postmarketing setting, serious bacterial, viral, and fungal opportunistic infections, and some fatal infections have been reported in patients receiving IL-17 inhibitors including COSENTYX. Cases of Hepatitis B virus reactivation have been reported [see Adverse Reactions (6.2)].
Exercise caution when considering the use of COSENTYX in patients with a chronic infection or a history of recurrent infection. Instruct patients to seek medical advice if signs or symptoms suggestive of an infection occur. If a patient develops a serious infection, monitor the patient closely and discontinue COSENTYX until the infection resolves.
If signs of Hepatitis B virus reactivation occur, consult a hepatitis specialist. COSENTYX is not recommended for use in patients with active viral hepatitis.
Serious hypersensitivity reactions including anaphylaxis, angioedema, and urticaria have been reported in COSENTYX treated subjects in clinical trials and in the post-marketing setting [see Adverse Reactions (6.1, 6.2)]. If an anaphylactic or other serious allergic reaction occurs, immediately discontinue administration of COSENTYX and initiate appropriate therapy [see Contraindications (4)].
Evaluate patients for active or latent TB infection prior to initiating treatment with COSENTYX. Avoid administration of COSENTYX to patients with active TB infection. Initiate treatment of latent TB prior to administering COSENTYX. Consider anti-TB therapy prior to initiation of COSENTYX in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Monitor patients closely for signs and symptoms of active TB during and after treatment.
In the postmarketing setting, cases were reported where patients with a history of latent tuberculosis (TB) who were treated with COSENTYX developed active TB.
Inflammatory Bowel Disease (IBD) exacerbations, in some cases serious and/or leading to discontinuation of COSENTYX, occurred in COSENTYX treated subjects during clinical trials in PsO, PsA, AS, nr-axSpA, and HS. In adult subjects with HS, the incidence of IBD was higher in subjects who received COSENTYX 300 mg every 2 weeks (Ulcerative Colitis [UC] 1 case, EAIR 0.2/100 subject-years; Crohn`s Disease [CD] 1 case, EAIR 0.2/100 subject-years) compared to subjects who received COSENTYX 300 mg every 4 weeks (IBD 1 case, EAIR 0.2/100 subject-years). In addition, new onset IBD cases occurred in subjects treated with COSENTYX in clinical trials. In an exploratory trial in 59 subjects with active Crohn’s disease [COSENTYX is not approved for the treatment of Crohn`s disease], there were trends toward greater disease activity and increased adverse reactions in subjects treated with COSENTYX as compared to placebo-treated subjects.
Exercise caution when prescribing COSENTYX to patients with IBD. Patients treated with COSENTYX should be monitored for signs and symptoms of IBD [see Adverse Reactions (6.1)].
In postmarketing reports, cases of severe eczematous eruptions, including atopic dermatitis-like eruptions, dyshidrotic eczema, and erythroderma, were reported in patients receiving COSENTYX; some cases resulted in hospitalization. The onset of eczematous eruptions was variable, ranging from days to months after the first dose of COSENTYX.
Treatment may need to be discontinued to resolve the eczematous eruption. Some patients were successfully treated for eczematous eruptions while continuing COSENTYX.
The removable caps of the COSENTYX 150 mg/mL Sensoready pen and the COSENTYX 1 mL and 0.5 mL prefilled syringes contain natural rubber latex, which may cause a hypersensitivity reaction in latex-sensitive individuals. The safe use of COSENTYX 150 mg/mL Sensoready pen or 1 mL and 0.5 mL prefilled syringes in latex-sensitive individuals has not been studied.
Prior to initiating therapy with COSENTYX, consider completion of all age-appropriate immunizations according to current immunization guidelines. COSENTYX may alter a patient’s immune response to live vaccines. Avoid use of live vaccines in patients treated with COSENTYX [see Clinical Pharmacology (12.2)].
Animal studies have not been conducted to evaluate the carcinogenic or mutagenic potential of COSENTYX. Some published literature suggests that IL-17A directly promotes cancer cell invasion in vitro, whereas other reports indicate IL-17A promotes T-cell mediated tumor rejection. Depletion of IL-17A with a neutralizing antibody inhibited tumor development in mice. The relevance of experimental findings in mouse models for malignancy risk in humans is unknown.
No effects on fertility were observed in male and female mice that were administered a murine analog of secukinumab at subcutaneous doses up to 150 mg/kg once weekly prior to and during the mating period.
In the event of overdosage, it is recommended that the patient be monitored for any signs or symptoms of adverse reactions and appropriate symptomatic treatment be instituted. Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdose management recommendations.
COSENTYX is contraindicated in patients with a previous serious hypersensitivity reaction to secukinumab or to any of the excipients in COSENTYX. Cases of anaphylaxis and angioedema have been reported during treatment with COSENTYX [see Warnings and Precautions (5.2)].
Secukinumab is a human IgG1 monoclonal antibody that selectively binds to the interleukin-17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Secukinumab inhibits the release of proinflammatory cytokines and chemokines.
Elevated levels of IL-17A are found in psoriatic plaques and in HS lesions. Treatment with COSENTYX may reduce epidermal neutrophils and IL-17A levels in psoriatic plaques. Serum levels of total IL-17A (free and secukinumab-bound IL-17A) measured at Week 4 and Week 12 were increased following secukinumab treatment. These pharmacodynamic activities are based on small exploratory trials. The relationship between these pharmacodynamic activities and the mechanism(s) by which secukinumab exerts its clinical effects is unknown.
Increased numbers of IL-17A producing lymphocytes and innate immune cells and increased levels of IL-17A have been found in the blood of patients with PsA and AS. Increased numbers of IL-17A producing lymphocytes have also been found in patients with nr-axSpA.
Healthy individuals who received a single 150 mg dose of COSENTYX 2 weeks prior to vaccination with a non-U.S.approved group C meningococcal polysaccharide conjugate vaccine and a non-U.S.-approved inactivated seasonal influenza vaccine had similar antibody responses compared to individuals who did not receive COSENTYX prior to vaccination. The clinical effectiveness of meningococcal and influenza vaccines has not been assessed in patients undergoing treatment with COSENTYX [see Warnings and Precautions (5.7)].
Pharmacokinetics Following Subcutaneous Administration
The observed pharmacokinetics (PK) of secukinumab administered subcutaneously in patients with PsO, PsA, AS and nraxSpA were similar. The secukinumab PK is also similar in pediatric patients with ERA and PsO for the same weight tiered dosing regimen.
The mean steady-state trough concentration of secukinumab was approximately 26% lower in HS subjects than that of PsO subjects.
Following a single subcutaneous dose of either 150 mg or 300 mg (administered as two injections of 150 mg) of COSENTYX in PsO subjects, secukinumab reached peak mean (± SD) serum concentrations (Cmax) of 13.7 ± 4.8 mcg/mL and 27.3 ± 9.5 mcg/mL, respectively, by approximately 6 days post dose.
Following multiple subcutaneous doses of COSENTYX (administered as one or two injections of 150 mg), the mean (± SD) serum trough concentrations of secukinumab ranged from 22.8 ± 10.2 mcg/mL (150 mg) to 45.4 ± 21.2 mcg/mL (300 mg) at Week 12. At the 300 mg dose at Week 4 and Week 12, the mean trough concentrations resulted from the Sensoready pen were approximately 30% higher than those from the prefilled syringe. Following multiple subcutaneous doses of 300 mg administered via the 300 mg/2 mL UnoReady pen, the mean serum trough concentrations of secukinumab were generally consistent with those in the previous Sensoready pen study used to deliver 300 mg.
Steady-state concentrations of secukinumab were achieved by Week 24 following the every 4-week COSENTYX dosing regimens. The mean (± SD) steady-state trough concentrations ranged from 16.7 ± 8.2 mcg/mL (150 mg) to 34.4 ± 16.6 mcg/mL (300 mg administered as two injections of 150 mg).
In healthy subjects and subjects with PsO, secukinumab bioavailability ranged from 55% to 77% following subcutaneous COSENTYX dose of 150 mg or 300 mg (administered as two injections of 150 mg).
Following subcutaneous administrations of 300 mg of COSENTYX at Weeks 0, 1, 2, 3, and 4 and then every 2 weeks thereafter, steady-state concentrations of secukinumab were achieved by Week 24 in both HS trials. The mean (± SD) steady-state trough concentrations were 55.7 ± 28.9 mcg/mL and 50.5 ± 28.2 mcg/mL in HS Trial 1 and HS Trial 2, respectively.
The mean volume of distribution during the terminal phase (Vz) following a single intravenous administration ranged from 7.10 to 8.60 L in PsO subjects.
Secukinumab concentrations in interstitial fluid in lesional and non-lesional skin of PsO subjects ranged from 27% to 40% of those in serum at 1 and 2 weeks after a single subcutaneous dose of COSENTYX 300 mg (administered as two injections of 150 mg).
Metabolism
The metabolic pathway of secukinumab has not been characterized. As a human IgG1κ monoclonal antibody secukinumab is expected to be degraded into small peptides and amino acids via catabolic pathways in the same manner as endogenous IgG.
Excretion
The mean systemic clearance (CL) ranged from 0.14 L/day to 0.22 L/day and the mean half-life ranged from 22 to 31 days in PsO subjects following intravenous and subcutaneous administration across all PsO trials.
In a population PK analysis, the mean systemic CL in subjects with HS was 0.26 L/day. The mean elimination half-life, as estimated from population PK analysis, was 23 days in HS subjects.
Secukinumab exhibited dose-proportional PK in subjects with PsO over a dose range from 25 mg (approximately 0.083 times the recommended dose) to 300 mg following subcutaneous administrations.
Secukinumab clearance and volume of distribution increase as body weight increases.
Patients with Hepatic or Renal Impairment
No formal trial of the effect of hepatic or renal impairment on the PK of secukinumab was conducted.
Geriatric Patients
Population PK analysis indicated that the clearance of secukinumab was not significantly influenced by age in adult subjects with PsO, PsA and AS. Subjects who are 65 years or older had apparent clearance of secukinumab similar to subjects less than 65 years old.
Pediatric Patients
In a pool of the two pediatric trials, subjects with moderate to severe PsO (6 years of age and older) were administered subcutaneous COSENTYX at the recommended pediatric dosing regimen. At Week 24, secukinumab steady state mean ± SD serum trough concentrations were 32.6 ± 10.8 mcg/mL (n = 8), 19.8 ± 6.96 mcg/mL (n = 24), and 27.3 ± 10.1 mcg/mL (n = 36), in subjects who weighed less than 25 kg and received 75 mg of subcutaneous COSENTYX, subjects who weighed at least 25 kg and less than 50 kg and received 75 mg of subcutaneous COSENTYX, and subjects who weighed at least 50 kg and received 150 mg of subcutaneous COSENTYX, respectively.
In a pediatric trial, JPsA and ERA patients (2 to less than 18 years of age) were administered subcutaneous COSENTYX at the recommended pediatric dosing regimen. At Week 24, patients who weighed at least 15 kg and less than 50 kg, and patients who weighed at least 50 kg had a mean ± SD steady-state trough concentration of 25.2 ± 5.45 mcg/mL (n = 10) and 27.9 ± 9.57 mcg/mL (n = 19), respectively.
Cytochrome P450 Substrates
In adult subjects with PsO, midazolam (CYP3A4 substrate) PK was similar when administered alone, or when administered following either a single or five weekly subcutaneous administrations of 300 mg of COSENTYX [see Drug Interactions (7)].
Pharmacokinetics Following Intravenous Administration
Following an intravenous administration of 1.75 mg/kg maintenance dose every four weeks, with or without a loading dose of 6 mg/kg at Day 0, the secukinumab concentrations [steady state trough secukinumab concentrations (Cmin,ss), mean secukinumab concentrations (Cavg,ss), and maximum secukinumab concentrations (Cmax,ss)] are estimated to be within the range of the steady state concentrations following subcutaneous administration of 150 mg and 300 mg doses of COSENTYX administered every four weeks.
The observed incidence of anti-drug antibodies is highly dependent on the sensitivity and specificity of the assay. Differences in assay methods preclude meaningful comparisons of the incidence of anti-drug antibodies (ADA) in the trials described below with the incidence of ADA in other trials, including those of COSENTYX (secukinumab).
The immunogenicity of COSENTYX was evaluated using an electrochemiluminescence-based bridging immunoassay.
Less than 1% of subjects treated with COSENTYX developed antibodies to secukinumab in up to 52 weeks of treatment. However, this assay has limitations in detecting anti-secukinumab antibodies in the presence of secukinumab; therefore, the incidence of antibody development might not have been reliably determined.
In up to 52 weeks of treatment in controlled trials in patients with PsO, PsA, AS, nr-axSpA, HS, pediatric PsO, JPsA and ERA [see Clinical Studies (14)], the incidence of anti-secukinumab antibodies (referred as ADA) formation was less than 1% (25 of 6268 total of subjects treated with COSENTYX). Of the subjects treated with COSENTYX who developed ADA, approximately 8% developed neutralizing antibodies. Because of the low occurrence of ADA, the effect of these antibodies on pharmacokinetics, pharmacodynamics, safety, or effectiveness of COSENTYX is unknown.
Advise the patient to read the FDA-approved patient labeling (Medication Guide and Instructions for Use).
Inform patients that COSENTYX may lower the ability of their immune system to fight infections and that serious infections, including opportunistic infections, may occur with the use of COSENTYX. Instruct patients of the importance of communicating any history of infections to the doctor and contacting their doctor if they develop any symptoms of infection [see Warnings and Precautions (5.1, 5.3)].
Advise patients to seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions [see Warnings and Precautions (5.2)].
Inform patients that skin reactions resembling eczema may occur with the use of COSENTYX. Instruct patients to seek medical advice if they develop signs or symptoms of eczema [see Warnings and Precautions (5.5)].
Advise latex-sensitive patients that the removal caps of the COSENTYX 150 mg/mL Sensoready pen and the COSENTYX 1 mL and 0.5 mL prefilled syringes contain natural rubber latex, which may cause an allergic reaction in latex-sensitive individuals [see Warnings and Precautions (5.6)].
Advise patients that vaccination with live vaccines is not recommended during COSENTYX treatment. Instruct patients to inform the healthcare practitioner that they are taking COSENTYX prior to a potential vaccination [see Warnings and Precautions (5.7)].
If a patient or caregiver is to subcutaneously administer COSENTYX using the UnoReady pen, Sensoready pen, or the prefilled syringe, instruct him/her in injection techniques and assess their ability to inject subcutaneously to ensure the proper administration of COSENTYX [see Dosage and Administration (2.2, 2.9), Medication Guide, and Instructions for Use].
For pediatric patients, inform patients and caregivers that pediatric patients should not self-administer COSENTYX.
Instruct patients or caregivers in the technique of proper syringe and needle disposal and advise them not to reuse these items. Instruct patients to inject the full amount of COSENTYX according to the directions provided in the Medication Guide and Instructions for Use.
Instruct patients to store COSENTYX in a refrigerator at 2°C to 8°C (36ºF to 46ºF) and to discard expired or unused COSENTYX.
Inform patients that if removed from refrigeration, COSENTYX 150 mg/mL Sensoready pens, 150 mg/mL and 75 mg/0.5 mL prefilled syringes may be stored for up to 4 days at room temperature not to exceed 86°F (30°C). Instruct patients to discard if kept outside of the refrigerator over 4 days [see How Supplied/Storage and Handling (16)].
