Secukinumab is a human IgG1 monoclonal antibody that selectively binds to the interleukin-17A (IL-17A) cytokine, inhibiting its interaction with the IL-17A receptor. Maintenance dosing is given once monthly. Secukinumab is useful in a variety of inflammatory disorders. Elevated concentrations of IL-17A are found in psoriatic plaques; secukinumab is approved to treat moderate to severe plaque psoriasis in patients 6 years and older who are candidates for systemic therapy or phototherapy. The drug is also indicated for treatment of adults with moderate to severe hidradenitis suppurativa, patients 2 years and older with active psoriatic arthritis (PsA), adults with ankylosing spondylitis (AS), adults with non-radiographic axial spondyloarthritis with objective signs of inflammation, and active enthesitis-related arthritis (ERA) in pediatric patients 4 years and older. In patients with PsA, the drug improves clinical signs and symptoms, inhibits the radiographic progression of structural joint damage, and improves physical function. In AS, clinical signs and symptoms and quality of life are improved with use of secukinumab. The ideal therapy for individual patients with plaque psoriasis, PsA, or AS is determined by treat to target strategies and severity of disease. While TNF-blockers are often first-line biologic treatments, the IL-inhibiting biologics may be considered when the patient has severe disease and either has contraindications/adverse reactions to TNF-blocking biologics or inadequate response. Similar to other interleukin inhibitors and biologic therapies, secukinumab use may increase the risk for serious infection and may cause hypersensitivity reactions. Use caution when considering secukinumab use in patients with active Crohn's disease due to the potential for inflammatory bowel disease activation.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. The solution should be free of visible particles, clear to slightly opalescent, and colorless to slightly yellow.
Intravenous Administration
-A 125 mg/5 mL injection solution in a single-dose vial is available for intravenous administration.
-The injection solution must be further diluted prior to use and administered by a health care professional in a health care setting.
-Use aseptic technique during preparation, dilution, and administration of the dose.
Prepare for Infusion Dilution:
-Using the patient's actual body weight, calculate the total volume of solution (in mL) required for the dose.
--Loading dose (6 mg/kg): Multiply patient's body weight (in kg) by 0.24 mL/kg.
-Maintenance dose (1.75 mg/kg): Multiply patient's body weight (in kg) by 0.07 mL/kg.
-Based on the total volume needed, remove the required number of vials (each vial contains 5 mL of solution) from the refrigerator and allow the vials to sit at room temperature of 20 to 25 degrees C (68 to 77 degrees F) for approximately 20 minutes.
Dilution:
-Select a volume of 0.9% Sodium Chloride Injection based on the dose and patient's body weight.
--Loading dose (6 mg/kg): Use a 100 mL infusion bag.
-Maintenance dose (1.75 mg/kg) and weight more than 52 kg: Use a 100 mL infusion bag.
-Maintenance dose (1.75 mg/kg) and weight 52 kg or less: Use a 50 mL infusion bag (if a 50 mL infusion bag is not available, aseptically remove and discard 50 mL from a 100 mL bag).
-From the infusion bag, withdraw and discard a volume of 0.9% Sodium Chloride Injection that is equal to the calculated volume of secukinumab solution required for the patient's dose.
-From the vial(s), withdraw the calculated volume of secukinumab solution and slowly add to the infusion bag. Discard any unused product that remains in the vial(s).
-Gently invert the bag to mix and to prevent foaming. Do not shake.
-Administer as soon as possible.
-Discard any unused solution left in an open vial after infusion preparation because the vial does not contain preservatives.
-Storage: If not used immediately, the diluted infusion solution may be stored at room temperature of 20 to 25 degrees C (68 to 77 degrees F) for no more than 4.5 hours from the start of preparation (piercing the first vial) to completion of the infusion. Alternatively, the diluted solution may be refrigerated at 2 to 8 degrees C (36 to 46 degrees F) for no more than 24 hours from the start of preparation (piercing the first vial) to completion of infusion. This time includes refrigeration of the diluted solution and the time needed to warm the infusion to room temperature. Protect from light during storage under refrigeration.
Intravenous infusion:
-Use only an infusion set with an in-line, sterile, non-pyrogenic, low protein-binding filter (pore size 0.2 micrometer).
-Administer the infusion IV over 30 minutes at a flow rate of 3.3 mL/minute for a 100 mL bag or 1.7 mL/minute for a 50 mL bag.
-After the infusion is complete, flush the line with at least 50 mL of 0.9% Sodium Chloride Injection to ensure the entire dose is administered.
-Do not infuse concomitantly in the same IV line with other medications. No physical or biochemical compatibility studies have been conducted.
Subcutaneous Administration
-Formulations for subcutaneous use include a prefilled syringe (75 mg/0.5 mL, 150 mg/mL, and 300 mg/2 mL), UnoReady pen (300 mg/2 mL), and Sensoready pen (150 mg/mL). All formulations are single-dose. Patients requiring a 300 mg dose may receive either a single 300 mg subcutaneous injection or two 150 mg subcutaneous injections.
-The prefilled syringe or pen injection may be self-administered by the adult patient after proper training. Self-administration is not recommended for pediatric patients; a properly trained adult caregiver should prepare and inject the pediatric patient.
-Review the manufacturer provided "Instructions for Use" for the specific device used to administer the dose.
Preparation for use of the prefilled syringes, Sensoready pen, or UnoReady pen:
-Prior to administration, remove the product from the refrigerator and allow time to reach room temperature (i.e., 15 to 30 minutes for Sensoready pen, 75 mg/0.5 mL or 150 mg/mL prefilled syringe; 30 to 45 minutes for UnoReady pen or the 300 mg/2 mL prefilled syringe). Do not remove the needle cap. Do not shake.
-Storage: If necessary, the Sensoready pen and the 75 mg/0.5 mL and 150 mg/mL prefilled syringe(s) may be stored for up to 4 days at room temperature not to exceed 30 degrees C (86 degrees F). Discard if the pen or syringe(s) have been kept out of the refrigerator and not used in over 4 days. Within the 4 days window, if unused and not stored above 30 degrees C (86 degrees F), the pen or syringe(s) may be returned to the refrigerator only 1 time and must be stored at 2 to 8 degrees C (36 to 46 degrees F) until used or expired. Write the date removed from and returned to the refrigerator in the space provided on the carton. The 300 mg/2 mL prefilled syringe and the UnoReady pen do not supply information for extended storage once removed from refrigeration.
Subcutaneous Injection:
-Do not shake the injection syringe or pen.
-Injections should be administered at a different location than was used for the previous injection.
-Select an injection site. Administration sites for self-administration include upper arms, thighs, and any quadrant of the abdomen. Caregivers and health care professionals may inject in the upper, outer arm. Do not administer into areas where the skin is tender, bruised, erythematous, indurated, or affected by scars, stretch marks, or psoriasis.
-Clean the injection site with an alcohol wipe and allow the site to dry.
-Remove the caps of the injection device as directed right before injection. The removable caps of the 75 mg/0.5 mL and 150 mg/mL prefilled syringes and the Sensoready pen contain natural rubber latex. Persons with a hypersensitivity to latex should not handle the caps of these injections.
--Prefilled syringe: Gently pinch the skin at the injection site. With the other hand insert the needle into the site skin at a 45-degree angle. Push the needle all the way in to ensure delivery of the full dose once injected. Inject as directed. Keep the plunger fully depressed and carefully pull the needle straight out from the injection site once complete.
-UnoReady and Sensoready pens: Apply the pen to the skin before injection at a 90-degree angle to the injection site and follow the pen-specific injection instructions provided by the manufacturer to complete the injection. Once the indicator window has stopped moving, the pen can be removed from the skin.
-Remove the device from the skin as directed. For the prefilled-syringe, slowly release the plunger once removed from the skin to allow the syringe guard to automatically cover the exposed needle.
-Once injection is complete, promptly dispose of used syringes, needles, or pens in an FDA-approved sharps container.
Hypersensitivity and dermatologic reactions can occur with secukinumab administration. During clinical trials, urticaria was reported in 0.6% and 1.2% of patients receiving the 300 mg and 150 mg dose, respectively. Case of anaphylaxis were also noted in secukinumab treated patients. During postmarketing use, cases of pyoderma gangrenosum and severe rash or eczematous eruptions (i.e., atopic dermatitis-like eruptions, dyshidrotic eczema, erythroderma) have been reported; some resulting in hospitalization. The onset of these eczematous eruptions was variable, ranging from days to months after the first secukinumab dose. If anaphylactoid reactions or other serious allergic reactions occur, discontinue secukinumab administration and institute appropriate therapy. However, in some patients, eczematous eruptions have been successfully treated while continuing to receive secukinumab.
Secukinumab administration may increase the risk of infection; serious, sometimes fatal infections have been reported. During placebo-controlled clinical trials in plaque psoriasis, infections were reported in 28.7% of patients treated with secukinumab compared to 18.9% of patients in the placebo group. Serious infections occurred in 0.14% of patients in the secukinumab group compared to 0.3% in the placebo group. During the entire treatment period studied (up to 52 weeks for most patients), infections were reported in 47.5% and serious infections in 1.2% of secukinumab patients treated for plaque psoriasis. In the open-label extension (median follow-up of 3.9 years), 74% of secukinumab recipients reported an infection and 4.5% developed a serious infection (including sepsis n = 5). Study data found the incidence of Candida infections, herpes infections, staphylococcal skin infections, and infections requiring treatment increased as secukinumab serum concentration increased. In pediatric trials, 1 case of methicillin-resistant Staphylococcus aureus (MRSA) toxic shock syndrome (TSS) was reported in a secukinumab-treated patient. Infections reported in more than 1% of adult patients in the trials for moderate to severe plaque psoriasis, and reported at incidences greater than with placebo, included naso-pharyngitis (11.4% for 300 mg dose and 12.3% for 150 mg dose), upper respiratory tract infection (2.5% for 300 mg dose and 3.2% for 150 mg dose), rhinitis (1.4% for 150 mg and 300 mg doses), oral ulceration (reported as oral herpes, 1.3% for 300 mg dose and 0.1% for 150 mg dose), and pharyngitis (1.2% for 300 mg dose and 1% for 150 mg dose). Rhinorrhea also was reported during clinical trials at incidences higher than with placebo (1.2% for 300 mg dose and 0.3% for 150 mg dose). Sinusitis, tinea pedis, ocular infection (reported as conjunctivitis), tonsillitis, oral candidiasis, impetigo, otitis media, and otitis externa were reported in less than 1% of patients during placebo-controlled secukinumab clinical trials. During a 16-week placebo-controlled clinical trial in patients with hidradenitis suppurativa, a higher incidence of fungal infections were observed in patients receiving 300 mg every 2 weeks (5.3%) than in those receiving 300 mg every 4 weeks (4.2%) or the placebo (2.8%). Additionally, with longer exposure, the rate of fungal infections remained higher for the every 2 week dosing regimen (14.7 per 100 patient-years) than for the every 4 week dosing regimen (10.1 per 100 patient-years). Most of the cases were not serious and resolved with antifungal treatment. In placebo-controlled clinical trials in psoriatic arthritis, infections were reported in 29% of secukinumab patients vs. 26% of placebo patients. A similar risk of infection was reported in placebo-controlled trials in patients with ankylosing spondylitis with infection reported in 31% of secukinumab patients vs. 18% of placebo patients. A higher incidence of infection was observed among non-radiographic axial spondyloarthritis patients who received a secukinumab regimen with a loading dosage compared to those without a loading dosage at an incidence of 92 per 100 patient-years versus 72 per 100 patient-years, respectively. Reported infections included naso-pharyngitis, upper respiratory tract infection, and urinary tract infection. Instruct patients to seek medical advice if signs or symptoms of infection develop. If a patient develops a serious infection, discontinue secukinumab until the infection resolves.
Gastrointestinal (GI) events have been reported with the use of secukinumab. During clinical trials of plaque psoriasis, diarrhea was reported in 4.1% and 2.6% of patients receiving the 300 mg and 150 mg dose, respectively. Inflammatory bowel disease was reported in less than 1% of patients. A higher incidence of GI disorders, including gastritis, lower abdominal pain, colitis, diarrhea, and hematochezia, was observed among non-radiographic axial spondyloarthritis patients who received a secukinumab regimen with a loading dosage regimen compared to those without a loading dosage regimen at an incidence of 27 per 100 patient-years versus 22 per 100 patient-years. Cases of Crohn's disease exacerbations and inflammatory bowel disease, some serious and leading to treatment discontinuation, were reported during secukinumab clinical trials. In patients treated for plaque psoriasis (n = 3,430), 3 cases (0.11 per 100 patient-years) of exacerbation of Crohn's disease, 2 cases (0.08 per 100 patient-years) of exacerbation of ulcerative colitis, and 2 cases (0.08 per 100 patient-years) of new-onset ulcerative colitis were reported. No cases were reported in patients receiving placebo (n = 793). There were 3 cases of inflammatory bowel disease in patients in psoriatic arthritis clinical trials (1 received placebo). Among 571 patients treated for ankylosing spondylitis, 5 cases of Crohn's disease (0.7 per 100 patient-years) and 3 cases of ulcerative colitis (0.4 per 100 patient-years) were reported. New-onset disease was reported in 1 of the Crohn's cases and in 2 of the ulcerative colitis cases. In an open-labeled hidradenitis suppurativa trial, 5 (0.7%) inflammatory bowel disease reactions were reported, all of which were serious and led to withdrawal of the trial drug. Additionally, all 5 reactions occurred in patients receiving 300 mg every 2 weeks; there were no cases in patients treated with 300 mg every 4 weeks. In an exploratory study involving patients (n = 59) with active Crohn's disease, there was an observed trend towards increased disease activity and adverse events in the secukinumab group compared to the placebo group.
During secukinumab clinical trials, elevated hepatic enzymes were reported in less than 1% of patients.
Neutropenia was reported in less than 1% of adults during secukinumab clinical trials. Most cases were transient and reversible, and no serious infections were associated with the cases of neutropenia. In the adult psoriasis trial open-label extension (median follow-up of 3.9 years), neutropenia was reported in 1% of secukinumab recipients. Some cases of serious infections were associated with the neutropenia; however, a causal relationship has not been established. In the pediatric safety pool, Grade 2 neutropenia (defined as 1,000 to 1,499 cells/mm3) was observed in 11% of patients who received at least 1 secukinumab dose during the treatment period. In the pediatric plaque psoriasis trial, Grade 2 neutropenia was reported in 4% of patients treated with secukinumab for up to 12 weeks. No serious infections were associated with cases of neutropenia in pediatric patients.
The development of immunogenicity (antibody formation) may occur with the use of secukinumab. During clinical trials of up to 52 weeks of treatment, less than 1% of patients developed antibodies to secukinumab. Of the patients who developed antibodies to secukinumab, approximately 50% had neutralizing antibodies; however, neutralizing antibodies were not associated with loss of efficacy. The assay used to detect secukinumab antibodies, an electrochemiluminescence-based bridging immunoassay, has limitations in detecting anti-secukinumab antibodies in the presence of secukinumab; therefore, the incidence of antibody development may not have been reliably determined. Furthermore, the detection of antibodies is dependent on the sensitivity and specificity of the assay, and the incidence of positive antibodies may be influenced by assay methodology, sample handling, the timing of sample collection, concomitant medications, and underlying disease. Therefore, the incidence of antibody formation to secukinumab cannot be directly compared to other products.
Secukinumab therapy may increase the risk of infection. In clinical trials, a higher rate of infections was reported with secukinumab compared to placebo. Additionally, serious and some fatal infections have been reported during postmarketing use of the drug. Use caution when administering secukinumab to patients with a chronic infection or a history of recurrent infection. If a patient develops a serious infection while receiving secukinumab, monitor the patient closely and discontinue therapy until the infection resolves.
Secukinumab should not be administered to patients with active tuberculosis infection. Evaluate patients for tuberculosis infection prior to treatment with secukinumab. Treatment of latent tuberculosis should be initiated prior to treatment with secukinumab, and antituberculosis therapy should be considered prior to initiating treatment with secukinumab in patients with a history of latent or active tuberculosis in whom an adequate treatment course cannot be confirmed. Monitor patients closely for signs and symptoms of active tuberculosis infection during and after treatment with secukinumab.
Use secukinumab cautiously in patients with inflammatory bowel disease (IBD) including active Crohn's disease or a history of ulcerative colitis. During secukinumab clinical trials, exacerbations of IBD, in some cases serious and leading to treatment discontinuation, were reported. In adults with hidradenitis suppurativa, the incidence of IBD was higher in patients who received secukinumab 300 mg every 2 weeks than in those who received 300 mg every 4 weeks. Cases of new onset IBD also were reported in clinical trials. Trends towards greater disease activity and increased adverse events were reported in a small study of patients with active Crohn's disease receiving secukinumab. Monitor patients closely for signs and symptoms of IBD during secukinumab treatment.
Complete all age appropriate vaccinations as recommended by current immunization guidelines prior to initiating secukinumab therapy. Avoid vaccination of secukinumab recipients with live virus vaccines, as patients treated with secukinumab may not elicit an immune response sufficient to prevent disease.
Secukinumab is contraindicated in patients with a history of hypersensitivity to secukinumab or to any of the excipients in the formulation. The removable caps of the 75 mg/0.5 mL and 150 mg/mL prefilled syringes and the Sensoready pen contain natural rubber latex. The safe use of these products has not been studied in patients with latex hypersensitivity. Using the 75 mg/0.5 mL or 150 mg/mL prefilled syringes or the Sensoready pen in latex-sensitive patients may result in an allergic reaction.
There are no adequate or well-controlled studies of secukinumab in pregnant women. A study in pregnant cynomolgus monkeys given weekly secukinumab doses up to 30 times the maximum recommended human dose found no evidence of malformations or embryo-fetal toxicity. Secukinumab should only be used during pregnancy if the benefit justifies the potential risk to the fetus.
It is not known whether secukinumab is excreted in human milk or absorbed systemically after ingestion. Use caution when administering secukinumab to a nursing woman. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Before starting secukinumab, test potential drug recipients for hepatitis B (surface antigen and core antibody), hepatitis C (IgG), and HIV serum status (HIV-1 and HIV-2 antibodies and HIV-1 antigen). Consider ongoing screening (e.g., annually) in people who are at increased risk for HIV, hepatitis B, or hepatitis C infection. Retest for HIV infection in any person who displays symptoms or other conditions that may suggest HIV seroconversion or infection. In patients found to be infected with HIV, consider involving relevant specialists to ensure HIV viral load is suppressed on antiretroviral therapy. Similarily, retest for viral hepatitis in any person who develops unexplained elevations in hepatic enzymes. It is recommended to consult a hepatologist when using a biological therapy in patients who are infected with hepatitis B or C, whether newly diagnosed or chronically infected.
Patients who undergo surgery while taking a biologic therapy, such as secukinumab, may be at greater risk for postoperative infections. In patients undergoing elective surgery, balance the risk of postoperative infection against the risk of developing a severe or unstable disease by stopping the biologic therapy. When possible, it is advised to stop the biologic therapy 3- to 5-times the half-live or the length of the treatment cycle (whichever is longer) between the last dose and the planned surgery. Restart the biologic therapy postoperatively if there is no evidence of infection and wound healing is satisfactory.
Treatment with secukinumab has been associated with cases of serious rash, including atopic dermatitis-like eruptions, dyshidrotic eczema, and erythroderma; some cases requiring hospitalization. The onset of the these eczematous eruptions was variable, ranging from days to months after the first secukinumab dose. In some patients, the reactions were successfully treated while continuing to receive secukinumab; however, treatment may need to be discontinued to resolve the eczematous eruption.
General Dosing Information
-Evaluate patients for active or latent tuberculosis (TB) infection prior to secukinumab initiation. Do not initiate in patients with active TB infection. Initiate treatment of latent TB before starting secukinumab.
-Complete all age-appropriate vaccinations according to current immunization guidelines before initiating treatment with secukinumab.
For the treatment of moderate to severe plaque psoriasis in persons who are candidates for systemic therapy or phototherapy:
Subcutaneous dosage:
Adults: 300 mg subcutaneously at Weeks 0, 1, 2, 3, and 4, then 300 mg subcutaneously every 4 weeks. A dose of 150 mg may be acceptable for some.
Children and Adolescents 6 to 17 years weighing 50 kg or more: 150 mg subcutaneously at Weeks 0, 1, 2, 3, and 4, then 150 mg subcutaneously every 4 weeks.
Children and Adolescents 6 to 17 years weighing less than 50 kg: 75 mg subcutaneously at Weeks 0, 1, 2, 3, and 4, then 75 mg subcutaneously every 4 weeks.
For the treatment of active psoriatic arthritis:
NOTE: May be administered with or without methotrexate.
-for the treatment of active psoriatic arthritis without coexistent moderate to severe plaque psoriasis:
Subcutaneous dosage:
Adults: 150 mg subcutaneously every 4 weeks, or may initiate with a loading dose of 150 mg subcutaneously at Weeks 0, 1, 2, 3, and 4, then 150 mg subcutaneously every 4 weeks. Consider increasing the dose to 300 mg subcutaneously every 4 weeks if active disease persists.
Children and Adolescents 2 to 17 years weighing 50 kg or more: 150 mg subcutaneously at Weeks 0, 1, 2, 3, and 4, then 150 mg subcutaneously every 4 weeks.
Children and Adolescents 2 to 17 years weighing 15 to 49 kg: 75 mg subcutaneously at Weeks 0, 1, 2, 3, and 4, then 75 mg subcutaneously every 4 weeks.
Intravenous dosage:
Adults: 1.75 mg/kg IV infusion every 4 weeks, or may initiate with a loading dose of 6 mg/kg IV infusion at Week 0, then 1.75 mg/kg IV infusion every 4 weeks for maintenance. Total doses exceeding 300 mg per infusion are not recommended for the 1.75 mg/kg maintenance dose.
-for the treatment of active psoriatic arthritis with coexistent moderate to severe plaque psoriasis:
Subcutaneous dosage:
Adults: 300 mg subcutaneously at Weeks 0, 1, 2, 3, and 4, then 300 mg subcutaneously every 4 weeks. A dose of 150 mg may be acceptable for some.
Children and Adolescents 2 to 17 years weighing 50 kg or more: 150 mg subcutaneously at Weeks 0, 1, 2, 3, and 4, then 150 mg subcutaneously every 4 weeks.
Children and Adolescents 2 to 17 years weighing 15 to 49 kg: 75 mg subcutaneously at Weeks 0, 1, 2, 3, and 4, then 75 mg subcutaneously every 4 weeks.
Intravenous dosage:
Adults: 1.75 mg/kg IV infusion every 4 weeks, or may initiate with a loading dose of 6 mg/kg IV infusion at Week 0, then 1.75 mg/kg IV infusion every 4 weeks for maintenance. Total doses exceeding 300 mg per infusion are not recommended for the 1.75 mg/kg maintenance dose.
For the treatment of active ankylosing spondylitis:
Subcutaneous dosage:
Adults: 150 mg subcutaneously every 4 weeks, or may initiate with a loading dose of 150 mg subcutaneously at Weeks 0, 1, 2, 3, and 4, then 150 mg subcutaneously every 4 weeks. Consider increasing the dose to 300 mg subcutaneously every 4 weeks if active disease persists. In clinical studies, patients were allowed to continue any of the following medications: sulfasalazine, weekly methotrexate, prednisone or prednisone equivalent (up to 10 mg/day), and any non-steroidal anti-inflammatory medications (NSAIDs).
Intravenous dosage:
Adults: 1.75 mg/kg IV infusion every 4 weeks, or may initiate with a loading dose of 6 mg/kg IV infusion at Week 0, then 1.75 mg/kg IV infusion every 4 weeks for maintenance. Total doses exceeding 300 mg per IV infusion are not recommended for the 1.75 mg/kg maintenance dose.
For the treatment of active, non-radiographic axial spondyloarthritis with objective signs of inflammation:
Subcutaneous dosage:
Adults: 150 mg subcutaneously every 4 weeks, or may initiate with a loading dose of 150 mg subcutaneously at Weeks 0, 1, 2, 3, and 4, then 150 mg subcutaneously every 4 weeks. In a clinical trial, patients with active non-radiographical axial spondyloarthritis were allowed to receive concomitant therapy with non-steroidal anti-inflammatory drugs (NSAIDs) and disease-modifying antirheumatic drugs (DMARDs).
Intravenous dosage:
Adults: 1.75 mg/kg IV infusion every 4 weeks, or may initiate with a loading dose of 6 mg/kg IV infusion at Week 0, then 1.75 mg/kg IV infusion every 4 weeks for maintenance. Total doses exceeding 300 mg per IV infusion are not recommended for the 1.75 mg/kg maintenance dose.
For the treatment of juvenile enthesitis-related arthritis:
Subcutaneous dosage:
Children and Adolescents 4 to 17 years weighing 50 kg or more: 150 mg subcutaneously at Weeks 0, 1, 2, 3, and 4. Then give 150 mg subcutaneously every 4 weeks thereafter.
Children and Adolescents 4 to 17 years weighing 15 to 49 kg: 75 mg subcutaneously at Weeks 0, 1, 2, 3, and 4. Then give 75 mg subcutaneously every 4 weeks thereafter.
For the treatment of moderate to severe hidradenitis suppurativa:
Subcutaneous dosage:
Adults: 300 mg subcutaneously at Weeks 0, 1, 2, 3, and 4, then 300 mg subcutaneously every 4 weeks. Consider increasing the dose to 300 mg subcutaneously every 2 weeks if the response to treatment is inadequate.
Maximum Dosage Limits:
-Adults
300 mg per dose subcutaneously; 6 mg/kg IV for loading dose and 1.75 mg/kg/dose (not to exceed 300 mg) IV for maintenance.
-Geriatric
300 mg per dose subcutaneously; 6 mg/kg IV for loading dose and 1.75 mg/kg/dose (not to exceed 300 mg) IV for maintenance.
-Adolescents
weighing 50 kg or more: 150 mg per dose subcutaneously; safety and efficacy have not been established for IV.
weighing less than 50 kg: 75 mg per dose subcutaneously; safety and efficacy have not been established for IV.
-Children
2 to 12 years weighing 50 kg or more: 150 mg per dose subcutaneously; safety and efficacy have not been established for IV.
2 to 12 years weighing 15 to 49 kg: 75 mg per dose subcutaneously; safety and efficacy have not been established for IV.
1 year or weighing less than 15 kg: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.
*non-FDA-approved indication
Abatacept: (Major) Concomitant use of abatacept with biological DMARDs, such as secukinumab, is not recommended because of the possibility of additive immunosuppression and increased risk of infection. There is insufficient experience to assess the safety and efficacy of abatacept administered concurrently with secukinumab.
Alfentanil: (Moderate) If secukinumab is initiated or discontinued in a patient taking alfentanil, monitor for altered patient response to alfentanil; alfentanil dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during secukinumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as alfentanil.
Bacillus Calmette-Guerin Vaccine, BCG: (Major) Do not administer live vaccines to secukinumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving secukinumab. Before initiation of secukinumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Secukinumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased. Similar antibody responses were seen when healthy individuals who received a single 150 mg dose of secukinumab 2 weeks before vaccination with a non-US approved group C meningococcal polysaccharide conjugate vaccine and a non-US approved inactivated seasonal influenza vaccine. The efficacy of meningococcal and influenza vaccines has not been evaluated in patients undergoing treatment with secukinumab.
Baricitinib: (Major) Concomitant use of baricitinib with biologic DMARDs, such as secukinumab, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Baricitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Canakinumab: (Major) Avoid the concomitant use of canakinumab with other interleukin inhibitors, such as secukinumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Carbamazepine: (Moderate) If secukinumab is initiated or discontinued in a patient taking carbamazepine, monitor carbamazepine concentrations; carbamazepine dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during secukinumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as carbamazepine. These interactions remain theoretical. Results from a drug-drug interaction study in subjects with moderate to severe psoriasis showed no clinically relevant interaction for drugs metabolized by CYP3A4.
Chikungunya Vaccine, Live: (Major) Do not administer live vaccines to secukinumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving secukinumab. Before initiation of secukinumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Secukinumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased. Similar antibody responses were seen when healthy individuals who received a single 150 mg dose of secukinumab 2 weeks before vaccination with a non-US approved group C meningococcal polysaccharide conjugate vaccine and a non-US approved inactivated seasonal influenza vaccine. The efficacy of meningococcal and influenza vaccines has not been evaluated in patients undergoing treatment with secukinumab.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Cisapride: (Moderate) If secukinumab is initiated or discontinued in a patient taking cisapride, monitor for altered patient response to cisapride; cisapride dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during secukinumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as cisapride.
Cyclosporine: (Moderate) If secukinumab is initiated or discontinued in a patient taking cyclosporine, monitor cyclosporine concentrations; cyclosporine dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during secukinumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as cyclosporine. These interactions remain theoretical. Results from a drug-drug interaction study in subjects with moderate to severe psoriasis showed no clinically relevant interaction for drugs metabolized by CYP3A4.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Dextromethorphan; Quinidine: (Moderate) If secukinumab is initiated or discontinued in a patient taking quinidine, monitor for altered patient response to quinidine; quinidine dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during secukinumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as quinidine.
Ethosuximide: (Moderate) If secukinumab is initiated or discontinued in a patient taking ethosuximide, monitor ethosuximide concentrations; ethosuximide dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during secukinumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as ethosuximide. These interactions remain theoretical. Results from a drug-drug interaction study in subjects with moderate to severe psoriasis showed no clinically relevant interaction for drugs metabolized by CYP3A4.
Everolimus: (Moderate) Monitor everolimus whole blood trough concentrations as appropriate if treatment with secukinumab is initiated for a patient on chronic everolimus therapy. The dose of everolimus may need to be increased. Everolimus is a sensitive CYP3A4 substrate. During chronic inflammation, increased levels of certain cytokines can decrease the formation of CYP450 enzymes. Thus, the formation of CYP3A4 could be normalized during secukinumab administration. The addition of secukinumab to everolimus therapy may increase the metabolism of everolimus and decrease everolimus blood concentrations.
Fentanyl: (Moderate) If secukinumab is initiated or discontinued in a patient taking fentanyl, monitor for altered patient response to fentanyl; fentanyl dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during secukinumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as fentanyl.
Fosphenytoin: (Moderate) If secukinumab is initiated or discontinued in a patient taking fosphenytoin, monitor phenytoin concentrations; fosphenytoin dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during secukinumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as fosphenytoin.
Intranasal Influenza Vaccine: (Major) Do not administer live vaccines to secukinumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving secukinumab. Before initiation of secukinumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Secukinumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased. Similar antibody responses were seen when healthy individuals who received a single 150 mg dose of secukinumab 2 weeks before vaccination with a non-US approved group C meningococcal polysaccharide conjugate vaccine and a non-US approved inactivated seasonal influenza vaccine. The efficacy of meningococcal and influenza vaccines has not been evaluated in patients undergoing treatment with secukinumab.
Live Vaccines: (Major) Do not administer live vaccines to secukinumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving secukinumab. Before initiation of secukinumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Secukinumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased. Similar antibody responses were seen when healthy individuals who received a single 150 mg dose of secukinumab 2 weeks before vaccination with a non-US approved group C meningococcal polysaccharide conjugate vaccine and a non-US approved inactivated seasonal influenza vaccine. The efficacy of meningococcal and influenza vaccines has not been evaluated in patients undergoing treatment with secukinumab.
Macitentan: (Major) Avoid coadministration of macitentan with secukinumab due to the potential for increases in macitentan exposure and adverse effects. Macitentan is a CYP3A4 and CYP2C9 substrate and secukinumab is a dual moderate CYP3A4 and CYP2C9 inhibitor. Concomitant use is predicted to increase macitentan exposure approximately 4-fold.
Macitentan; Tadalafil: (Major) Avoid coadministration of macitentan with secukinumab due to the potential for increases in macitentan exposure and adverse effects. Macitentan is a CYP3A4 and CYP2C9 substrate and secukinumab is a dual moderate CYP3A4 and CYP2C9 inhibitor. Concomitant use is predicted to increase macitentan exposure approximately 4-fold.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) Do not administer live vaccines to secukinumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving secukinumab. Before initiation of secukinumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Secukinumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased. Similar antibody responses were seen when healthy individuals who received a single 150 mg dose of secukinumab 2 weeks before vaccination with a non-US approved group C meningococcal polysaccharide conjugate vaccine and a non-US approved inactivated seasonal influenza vaccine. The efficacy of meningococcal and influenza vaccines has not been evaluated in patients undergoing treatment with secukinumab.
Measles/Mumps/Rubella Vaccines, MMR: (Major) Do not administer live vaccines to secukinumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving secukinumab. Before initiation of secukinumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Secukinumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased. Similar antibody responses were seen when healthy individuals who received a single 150 mg dose of secukinumab 2 weeks before vaccination with a non-US approved group C meningococcal polysaccharide conjugate vaccine and a non-US approved inactivated seasonal influenza vaccine. The efficacy of meningococcal and influenza vaccines has not been evaluated in patients undergoing treatment with secukinumab.
Phenytoin: (Moderate) If secukinumab is initiated or discontinued in a patient taking phenytoin, monitor phenytoin concentrations; phenytoin dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during secukinumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as phenytoin.
Pimozide: (Moderate) If secukinumab is initiated or discontinued in a patient taking pimozide, monitor for altered patient response to pimozide; pimozide dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during secukinumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as pimozide.
Quinidine: (Moderate) If secukinumab is initiated or discontinued in a patient taking quinidine, monitor for altered patient response to quinidine; quinidine dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during secukinumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as quinidine.
Rotavirus Vaccine: (Major) Do not administer live vaccines to secukinumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving secukinumab. Before initiation of secukinumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Secukinumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased. Similar antibody responses were seen when healthy individuals who received a single 150 mg dose of secukinumab 2 weeks before vaccination with a non-US approved group C meningococcal polysaccharide conjugate vaccine and a non-US approved inactivated seasonal influenza vaccine. The efficacy of meningococcal and influenza vaccines has not been evaluated in patients undergoing treatment with secukinumab.
Sarilumab: (Major) Avoid using sarilumab with other biological DMARDs, such as secukinumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Major) Do not administer live vaccines to secukinumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving secukinumab. Before initiation of secukinumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Secukinumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased. Similar antibody responses were seen when healthy individuals who received a single 150 mg dose of secukinumab 2 weeks before vaccination with a non-US approved group C meningococcal polysaccharide conjugate vaccine and a non-US approved inactivated seasonal influenza vaccine. The efficacy of meningococcal and influenza vaccines has not been evaluated in patients undergoing treatment with secukinumab.
Smallpox Vaccine, Vaccinia Vaccine: (Major) Do not administer live vaccines to secukinumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving secukinumab. Before initiation of secukinumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Secukinumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased. Similar antibody responses were seen when healthy individuals who received a single 150 mg dose of secukinumab 2 weeks before vaccination with a non-US approved group C meningococcal polysaccharide conjugate vaccine and a non-US approved inactivated seasonal influenza vaccine. The efficacy of meningococcal and influenza vaccines has not been evaluated in patients undergoing treatment with secukinumab.
Tacrolimus: (Moderate) If secukinumab is initiated or discontinued in a patient taking tacrolimus, monitor tacrolimus concentrations; tacrolimus dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during secukinumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as tacrolimus. These interactions remain theoretical. Results from a drug-drug interaction study in subjects with moderate to severe psoriasis showed no clinically relevant interaction for drugs metabolized by CYP3A4.
Theophylline, Aminophylline: (Moderate) If secukinumab is initiated or discontinued in a patient taking aminophylline, monitor theophylline concentrations; aminophylline dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during secukinumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as aminophylline. (Moderate) If secukinumab is initiated or discontinued in a patient taking theophylline, monitor theophylline concentrations; theophylline dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during secukinumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as theophylline.
Thioridazine: (Moderate) Monitor for an altered patient response to thioridazine if coadministration with secukinumab is necessary. Secukinumab therapy may restore CYP450 activities to higher levels than pretreatment, leading to increased metabolism of CYP450 substrates as compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic index may have fluctuations in drug levels and therapeutic effect. Thioridazine is a CYP2D6 substrate and narrow therapeutic index drug.
Tizanidine: (Moderate) If secukinumab is initiated or discontinued in a patient taking tizanidine, monitor for altered patient response to tizanidine; tizanidine dose adjustments may be needed. The formation of CYP450 enzymes may be altered by increased concentrations of cytokines during chronic inflammation. Thus, the formation of CYP450 enzymes could be normalized during secukinumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as tizanidine.
Tocilizumab: (Major) Avoid using tocilizumab with other biological DMARDs, such as secukinumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Tofacitinib: (Major) Concomitant use of tofacitinib with biologic DMARDs, such as secukinumab, is not recommended because of the possibility of additive immunosuppression and increased infection risk. Tofacitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Typhoid Vaccine: (Major) Do not administer live vaccines to secukinumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving secukinumab. Before initiation of secukinumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Secukinumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased. Similar antibody responses were seen when healthy individuals who received a single 150 mg dose of secukinumab 2 weeks before vaccination with a non-US approved group C meningococcal polysaccharide conjugate vaccine and a non-US approved inactivated seasonal influenza vaccine. The efficacy of meningococcal and influenza vaccines has not been evaluated in patients undergoing treatment with secukinumab.
Upadacitinib: (Major) Concomitant use of upadacitinib with biologic DMARDs, such as secukinumab, is not recommended because of the possibility of increased immunosuppression and increased infection risk. Upadacitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs.
Varicella-Zoster Virus Vaccine, Live: (Major) Do not administer live vaccines to secukinumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving secukinumab. Before initiation of secukinumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Secukinumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased. Similar antibody responses were seen when healthy individuals who received a single 150 mg dose of secukinumab 2 weeks before vaccination with a non-US approved group C meningococcal polysaccharide conjugate vaccine and a non-US approved inactivated seasonal influenza vaccine. The efficacy of meningococcal and influenza vaccines has not been evaluated in patients undergoing treatment with secukinumab.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with secukinumab is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. Secukinumab is a moderate CYP3A4/CYP2C9/CYP1A2 inhibitor and warfarin is a CYP3A4/CYP2C9/CYP1A2 substrate.
Yellow Fever Vaccine, Live: (Major) Do not administer live vaccines to secukinumab recipients; no data are available regarding the risk of secondary transmission of infection by live vaccines in patients receiving secukinumab. Before initiation of secukinumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. Secukinumab recipients may receive inactivated vaccines, but the immune response to vaccines or toxoids may be decreased. Similar antibody responses were seen when healthy individuals who received a single 150 mg dose of secukinumab 2 weeks before vaccination with a non-US approved group C meningococcal polysaccharide conjugate vaccine and a non-US approved inactivated seasonal influenza vaccine. The efficacy of meningococcal and influenza vaccines has not been evaluated in patients undergoing treatment with secukinumab.
Secukinumab is a human IgG1 monoclonal antibody that selectively binds to the interleukin-17A (IL-17A) cytokine, inhibiting its interaction with the IL-17 receptor. A naturally occurring cytokine, IL-17A is involved in normal inflammatory and immune responses. IL-17A stimulates keratinocytes to secrete chemokines and other proinflammatory cells. Elevated concentrations of IL-17A are found in psoriatic plaques. Treatment with secukinumab inhibits the release of proinflammatory cytokines and chemokines and may reduce epidermal neutrophils and IL-17A concentrations in psoriatic plaques.
Secukinumab is administered subcutaneously or via intravenous infusion. The mean volume of distribution following a single intravenous dose in patients with plaque psoriasis ranges from 7.1 to 8.6 L. Secukinumab concentrations in the interstitial fluid in lesional and non-lesional skin of patients with plaque psoriasis ranges from 27% to 40% of serum concentrations at 1 and 2 weeks following a 300-mg subcutaneous dose. Although the metabolic pathway is not fully elucidated, secukinumab is expected to be degraded to small peptides and amino acids in the same manner as endogenous human IgG. Mean systemic clearance ranges from 0.14 to 0.22 L/day, and the mean half-life ranges from 22 to 31 days in patients with plaque psoriasis following intravenous and subcutaneous administration. In hidradenitis suppurativa patients, the mean systemic clearance is 0.26 L/day and the mean half-life is 23 days. Secukinumab exhibits dose-proportional pharmacokinetics.
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: None known
The formation of CYP450 enzymes can be altered by increased levels of certain cytokines (e.g., IL-1, IL-6, IL-10, TNF-alpha, IFN) during chronic inflammation. In theory, treatment with secukinumab might cause alteration of the formation of CYP450 enzymes. Upon initiation or discontinuation of secukinumab in patients who are receiving concomitant CYP450 substrates, particularly those with a narrow therapeutic index, consider monitoring for therapeutic effect or drug concentration and consider dosage adjustment as needed. Results from drug-drug interaction studies showed no clinically relevant interactions of secukinumab with drugs metabolized by CYP3A4.
-Route-Specific Pharmacokinetics
Intravenous Route
Secukinumab concentrations (i.e., steady-state trough concentrations, mean concentrations, and maximum concentrations) following intravenous administration of 1.75 mg/kg every 4 weeks, with and without a loading dose of 6 mg/kg at Week 0, are estimated to be within the range of steady-state concentrations observed following subcutaneous 150 mg and 300 mg doses administered every 4 weeks.
Subcutaneous Route
In healthy subjects and patients with plaque psoriasis (PsO), the bioavailability of secukinumab ranges from 55% to 77% following subcutaneous administration of the 150 mg or 300 mg dose (administered as two 150 mg injections). The peak mean (+/- SD) serum concentrations of secukinumab in patients with PsO after subcutaneous doses of 150 mg and 300 mg are 13.7 +/- 4.8 mcg/mL and 27.3 +/- 9.5 mcg/mL, respectively, and are reached in approximately 6 days. Following multiple subcutaneous doses of secukinumab (administered as 1 or 2 injections of 150 mg), the mean (+/- SD) serum trough concentrations at Week 12 are 22.8 +/- 10.2 mcg/mL for the 150 mg dose and 45.4 +/- 21.2 mcg/mL for the 300 mg dose. Evaluations of the 300 mg dose at Week 4 and Week 12 show the mean trough concentrations of the Sensoready pen approximately 30% higher than those from the prefilled syringe. Following multiple subcutaneous doses of 300 mg administered via the UnoReady pen, the mean serum trough concentrations were generally consistent with those observed with the Sensoready pen study used to deliver 300 mg doses. Steady-state concentrations are achieved by Week 24 following every 4 week administration. The mean (+/- SD) steady-state trough concentrations range from 16.7 +/- 8.2 mcg/mL (150 mg) to 34.4 +/- 16.6 mcg/mL (300 mg). Mean steady-state trough concentration are approximately 26% lower in patients with hidradenitis suppurativa (HS) than in those with PsO. Following subcutaneous administration of 300 mg at Weeks 0, 1, 2, 3, 4, and 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.
-Special Populations
Hepatic Impairment
No formal studies of the effect of hepatic impairment on the pharmacokinetics of secukinumab have been conducted.
Renal Impairment
No formal studies of the effect of renal impairment on the pharmacokinetics of secukinumab have been conducted.
Pediatrics
At the recommended dosing regimen, secukinumab mean trough concentrations at steady state were 32.6 mcg/mL in patients weighing less than 25 kg, 19.8 mcg/mL in patients weighing 25 to 49 kg, and 27.3 mcg/mL in patients weighing 50 kg or more during clinical trials for plaque psoriasis. Similarly, mean trough concentrations at steady state were 25.2 mcg/mL and 27.9 mcg/mL in patients weighing 15 to 49 kg and 50 kg or more, respectively, in trials for psoriatic and enthesitis-related arthritis.
Geriatric
The clearance of secukinumab is not significantly influenced by age in adults with plaque psoriasis.
Obesity
The volume of distribution and clearance of secukinumab increase as body weight increases.