Brodalumab is an injectable human IgG2 monoclonal antibody that binds to interleukin-17 receptor A (IL-17RA), and prevents IL-17 cytokines from activating the receptor. Brodalumab is used to treat adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy (UV light treatment) and have failed to respond, or have stopped responding to other systemic therapies. Suicidal ideation and behavior, including completed suicides, have occurred in patients treated with the drug during clinical trials. Patients with a history of suicidality or depression had an increased incidence risk for these events during treatment. A causal association between treatment with the drug and increased risk of suicidal ideation and behavior has not been established. Because of the observed risk of suicidal ideation and behavior, the labeling includes a Boxed Warning and the drug is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS), the SILIQ REMS Program. The FDA approved brodalumab in February 2017.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
NOTE: Brodalumab is only available through a restricted program called the SILIQ Risk Evaluation and Mitigation Strategy (REMS) Program. This REMS program was established because of the drugs association with suicidal ideation and behavior. Health care professionals who wish to prescribe brodalumab and pharmacies that dispense brodalumab must be certified in the SILIQ REMS Program. Patients receiving brodalumab must sign a Patient-Prescriber Agreement Form. For information regarding the SILIQ REMS program, visit the SILIQ REMS website or telephone the call center at 855-511-6135.
Route-Specific Administration
Injectable Administration
-Prior to administration, removed prefilled syringe from refrigerator and slowly allow the solution to reach room temperature (approximately 30 minutes). Do not use other methods to speed the warming process. Do not remove the gray needle cap from the prefilled syringe while allowing it to reach room temperature.
-Once brought to room temperature, do not place the prefilled syringe back into the refrigerator. If needed, the prefilled syringe may be stored at room temperature for up to 14 days. Any prefilled syringe that has been stored at room temperature for more than 14 days MUST be discarded.
-DO NOT shake the prefilled syringe.
-DO NOT use the prefilled syringe if it has been dropped on a hard surface. Use a new syringe and call 1-800-321-4576.
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit. The solution should be clear to slightly opalescent, colorless to slightly yellow, and may contain a few small translucent or white particles. Do not use if discolored, cloudy, or if foreign particulate matter is present.
Subcutaneous Administration
-Only an individual trained in subcutaneous drug delivery should administer the injection. A patient who is properly trained in injection technique may self-inject using the prefilled syringe, if the prescriber deems the action appropriate. However, the first injection needs to be under the supervision of a qualified healthcare professional.
-Remove the prefilled syringe from the refrigerated packaging by lifting on the syringe barrel; do not grab the plunger rod or the gray needle cap.
-Clean injection site with alcohol wipe and allow site to dry. Potential injection sites include the front part of the middle thigh, the abdominal region, and the outer area of the upper arm. DO NOT administer where skin is tender, bruised, red, hard, thick, scaly, or affected by psoriasis.
-After the prefilled syringe has reached room temperature, pull the gray needle cap straight off and away from your body. Discard needle cap in a sharps container.
-With one hand, pinch injection site to create a firm surface that is approximately 2 inches wide.
-With the other hand, insert needle into the skin at a 45 to 90 degree angle. Do not place finger on the plunger rod while inserting the needle.
-Using slow and constant pressure, push the plunger rod all the way down until it reaches the bottom. Instruct patients to inject the full contents of the prefilled syringe (1.5 mL).
-When done, release your thumb, and gently lift the syringe to pull the needle out of the skin.
-Inspect the syringe. The entire dose was not administered if there is still solution in the syringe barrel. Instruct the patient to call their health care provider if this occurs.
-Discard the syringe in a sharps container.
During clinical trials, an infection occurred in 25.4% of patients receiving brodalumab and 23.4% of patients in the placebo group; the incidence of serious infections was 0.5% for brodalumab and 0.2% for placebo. The majority of these infections did not require treatment discontinuation and consisted of upper respiratory tract infections, pharyngitis, naso-pharyngitis, bronchitis, influenza (1.3%), and urinary tract infections. Fungal infections were observed in 1.8% to 2.4% of drug recipients during clinical trials. These fungal infections were primarily non-serious mucosal and skin candida and tinea infections (i.e., cruris, pedis, versicolor); however, 1 patient developed cryptococcal meningitis which required brodalumab treatment discontinuation. Instruct patients to seek medical attention if signs or symptoms of an infection occur. If a patient develops a serious infection or is not responding to standard therapy for an infection, discontinue brodalumab until the infection resolves and monitor the patient closely.
Suicidal ideation and behavior, including completed suicides, have occurred in patients treated with brodalumab. Across the clinical development program for plaque psoriasis, 4,464 subjects were exposed to at least 1 dose of brodalumab. Of those 4,464 drug recipients, 34 subjects displayed suicidal ideation and behavior (0.37 per 100 subject-years), 6 attempted suicide, and 4 completed suicide. Of note, 8 of the 10 subjects who attempted or completed suicide had a previous history of depression or suicidal ideation and behavior. As a result of this data, brodalumab is only available through a restricted program called the SILIQ REMS Program. Health care providers and pharmacies must be registered in this program in order to prescribe and dispense brodalumab; patients must sign a Prescriber-Patient Agreement Form before receiving brodalumab. Advise patients and caregivers to seek medical attention for manifestations of suicidal ideation, new onset or worsening depression, anxiety, or other mood changes or emotional lability. If such events occur, re-evaluate the risk and benefits of continuing therapy and consider referral to a mental health professional, as appropriate.
During the 12-week randomized treatment period, neutropenia occurred in 0.7% of patients receiving brodalumab, with most cases of neutropenia being transient. In patients with a normal absolute neutrophil count (ANC) at baseline, 6.8% of brodalumab recipients experienced a reduction in ANC, compared to 3.3% for ustekinumab and 3.6% for placebo. Further, more subjects in the brodalumab group (0.5%) developed Grade 3 or higher neutropenia (less than 1000 cells/mm3) than in the ustekinumab or placebo group (0.2% for both). From treatment week 0 to the end of the trial, the exposure-adjusted rate of treatment-emergent neutropenia for brodalumab was 0.4 per 100 subject-years (0.1 per 100 subject-years for Grade 3 or higher neutropenia). No serious infections were associated with cases of neutropenia during clinical trials.
The development of immunogenicity (antibody formation) may occur with the use of brodalumab. During the 52-week treatment period approximately 3% of patients developed antibodies to brodalumab. Of those subjects who developed antibodies to the drug, none were classified as neutralizing (i.e., associated with reduced drug concentration and loss of efficacy). However, the assay used to detect neutralizing antibodies had limitations in the presence of brodalumab; therefore, the incidence of neutralizing antibody development may be underestimated. Further, 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, timing of sample collection, concomitant medications, and underlying disease. Therefore, the incidence of antibody formation to brodalumab cannot be directly compared to other products.
During the clinical development program for plaque psoriasis, which excluded subjects with active Crohn's disease, 1 patient developed Crohn's disease during treatment with brodalumab. In other trials, exacerbation of Crohn's disease was observed with use of the drug. Other gastrointestinal adverse events experienced by recipients of brodalumab during 12-week clinical trials included diarrhea (2.2%), oropharyngeal pain (2.1%), and nausea (1.9%).
During the 12-week clinical trials, arthralgia and myalgia were reported by 4.7% and 1.7% of brodalumab drug recipients, respectively. In addition, 1.5% of patients experienced an injection site reaction (i.e., bruising, bleeding, pain, erythema, pruritus).
Headache (4.3%) and fatigue (2.6%) were among the most frequently reported adverse events during brodalumab 12-week clinical trials.
Use of brodalumab is contraindicated in patients with Crohn's disease because the drug may cause worsening of the disease. Clinical trials excluded patients with active Crohn's disease; however, one study subject developed Crohn's disease while receiving brodalumab. In other trials, treatment with brodalumab was associated with an exacerbation of Crohn's disease. Discontinue brodalumab therapy in any drug recipient who develops signs of Crohn's disease.
Due to its effect on the immune system, brodalumab may increase the risk of developing an infection or reactivating a latent infection. Consider the risks and benefits before prescribing the drug to patients with chronic infections, history of recurrent infections, underlying conditions that may predispose them to infection (e.g., immunosuppression), or who live in certain infection endemic areas; these patients may not be appropriate candidates for brodalumab therapy. During 12-weak clinical trials, 25% of drug recipients developed an infection. Although most infections did not required discontinuation of therapy, treatment with brodalumab was associated with higher rates of serious infections (0.5%) and fungal infection (2.4%, including 1 case of cryptococcal meningitis) than were observed in subjects receiving placebo (0.2% and 0.9%, respectively). Instruct patients to seek medical attention if signs or symptoms of an infection occur. If a patient develops a serious infection or is not responding to standard therapy for an infection, discontinue brodalumab until the infection resolves and monitor the patient closely.
Avoid vaccination of brodalumab recipients with live virus vaccines. No data are available on the ability of live or inactive vaccines to elicit an immune response in patients being treated with brodalumab. Consider completing all age appropriate immunizations prior to initiating brodalumab therapy.
Evaluate all patients for tuberculosis before initiating brodalumab therapy; the drug must not be administered to patients with active tuberculosis infection. For patients with latent tuberculosis, treatment against the tuberculosis infection must be initiated prior to administering brodalumab. Use of antituberculosis therapy before brodalumab administration should also be considered for patients with a history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed. Monitor patients closely for signs and symptoms of active tuberculosis infection during and after treatment with brodalumab. Patients who have lived in tuberculosis endemic areas may not be appropriate candidates for use of the drug. Carefully consider the benefits and risks of therapy before drug initiation.
During clinical trials, brodalumab was associated with suicidal ideation and behavior, including 4 completed suicides. As a result, the drug is only available through a restricted program called the SILIQ REMS Program. Health care providers and pharmacies must be registered in this program in order to prescribe and dispense brodalumab; patients must sign a Prescriber-Patient Agreement Form before receiving brodalumab. Further analysis of study data showed increased incidence of suicidal ideation and behavior among drug recipients with a history of suicidality or depression as compared to recipients without such a history. Thus, a careful assessment of the risks and benefits of treatment is advised when considering use of brodalumab in patients with a history of depression or psychosis. Advise patients and caregivers to seek medical attention for manifestations of suicidal ideation, new onset or worsening depression, anxiety, or other mood changes. If such events occur, re-evaluate the risk and benefits of continuing therapy and consider referral to a mental health professional, as appropriate.
Safety and efficacy of brodalumab in pediatric patients (i.e., neonates, infants, children, adolescents) have not be established.
There are no data on the use of brodalumab during pregnancy and drug-related fetal risks are not known. Human IgG does cross the placental barrier; therefore, brodalumab may be transmitted from mother to fetus. No effects on neonatal development were observed when monkeys were administered the drug at dose up to 26-times the maximum recommended human dose (MRHD).
There are no data on the presence of brodalumab in human milk, the effects on breast-fed infants, or the effects on milk production. Consider the benefits of breast-feeding along with the mother's clinical need for brodalumab, and any potential adverse effects on the breast-fed infant from brodalumab or the underlying maternal condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.
Before starting brodalumab, 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 brodalumab, 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.
For the treatment of moderate to severe plaque psoriasis in persons who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies:
Subcutaneous dosage:
Adults: 210 mg subcutaneously at weeks 0, 1, and 2, then 210 mg subcutaneously every 2 weeks. Consider discontinuing therapy if an inadequate response has not been achieved after 12 to 16 weeks of treatment. Continued treatment beyond 16 weeks in persons who have not achieved an adequate response is not likely to result in clinical success.
Maximum Dosage Limits:
-Adults
210 mg/dose subcutaneously; maintenance therapy every 2 weeks.
-Geriatric
210 mg/dose subcutaneously; maintenance therapy every 2 weeks.
-Adolescents
Safety and efficacy have not been established.
-Children
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
Bacillus Calmette-Guerin Vaccine, BCG: (Major) Avoid administration of live vaccines to brodalumab recipients. Before initiation of brodalumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. No data are available on the response to live or inactive vaccines in patients receiving brodalumab therapy.
Canakinumab: (Major) Avoid the concomitant use of canakinumab with other interleukin inhibitors, such as brodalumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Carbamazepine: (Moderate) If brodalumab 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 brodalumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as carbamazepine.
Chikungunya Vaccine, Live: (Major) Avoid administration of live vaccines to brodalumab recipients. Before initiation of brodalumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. No data are available on the response to live or inactive vaccines in patients receiving brodalumab therapy.
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.
Cyclosporine: (Moderate) If brodalumab 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 brodalumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as cyclosporine.
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.
Erdafitinib: (Major) Avoid coadministration of erdafitinib and brodalumab due to the risk of increased plasma concentrations of erdafitinib. If concomitant use is unavoidable, closely monitor for erdafitinib-related adverse reactions and consider dose modifications as clinically appropriate. If brodalumab is discontinued, the dose of erdafitinib may be increased in the absence of drug-related toxicity. Erdafitinib is a CYP2C9 substrate and brodalumab is a moderate CYP2C9 inhibitor.
Ethosuximide: (Moderate) If brodalumab 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 brodalumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as ethosuximide.
Fosphenytoin: (Moderate) If brodalumab 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 brodalumab 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) Avoid administration of live vaccines to brodalumab recipients. Before initiation of brodalumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. No data are available on the response to live or inactive vaccines in patients receiving brodalumab therapy.
Live Vaccines: (Major) Avoid administration of live vaccines to brodalumab recipients. Before initiation of brodalumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. No data are available on the response to live or inactive vaccines in patients receiving brodalumab therapy.
Macitentan: (Major) Avoid coadministration of macitentan with brodalumab due to the potential for increases in macitentan exposure and adverse effects. Macitentan is a CYP3A4 and CYP2C9 substrate and brodalumab 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) Avoid administration of live vaccines to brodalumab recipients. Before initiation of brodalumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. No data are available on the response to live or inactive vaccines in patients receiving brodalumab therapy.
Measles/Mumps/Rubella Vaccines, MMR: (Major) Avoid administration of live vaccines to brodalumab recipients. Before initiation of brodalumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. No data are available on the response to live or inactive vaccines in patients receiving brodalumab therapy.
Phenytoin: (Moderate) If brodalumab 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 brodalumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as phenytoin.
Rotavirus Vaccine: (Major) Avoid administration of live vaccines to brodalumab recipients. Before initiation of brodalumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. No data are available on the response to live or inactive vaccines in patients receiving brodalumab therapy.
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) Avoid administration of live vaccines to brodalumab recipients. Before initiation of brodalumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. No data are available on the response to live or inactive vaccines in patients receiving brodalumab therapy.
Smallpox Vaccine, Vaccinia Vaccine: (Major) Avoid administration of live vaccines to brodalumab recipients. Before initiation of brodalumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. No data are available on the response to live or inactive vaccines in patients receiving brodalumab therapy.
Tacrolimus: (Moderate) If brodalumab 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 brodalumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as tacrolimus.
Theophylline, Aminophylline: (Moderate) If brodalumab 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 brodalumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as aminophylline. (Moderate) If brodalumab 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 brodalumab administration. In theory, clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as theophylline.
Typhoid Vaccine: (Major) Avoid administration of live vaccines to brodalumab recipients. Before initiation of brodalumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. No data are available on the response to live or inactive vaccines in patients receiving brodalumab therapy.
Upadacitinib: (Major) Do not use upadacitinib in combination with biologic immunosuppressives, such as brodalumab, 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. Most patients taking upadacitinib who developed serious infections were taking concomitant immunosuppressives such as methotrexate or corticosteroids.
Varicella-Zoster Virus Vaccine, Live: (Major) Avoid administration of live vaccines to brodalumab recipients. Before initiation of brodalumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. No data are available on the response to live or inactive vaccines in patients receiving brodalumab therapy.
Warfarin: (Moderate) Closely monitor the INR if coadministration of warfarin with brodalumab is necessary due to the potential for decreased warfarin efficacy; adjust the dose of warfarin as necessary. Inhibition of IL-17 signaling by brodalumab may restore CYP450 activities to higher levels leading to increased metabolism of drugs that are CYP450 substrates as compared to metabolism prior to treatment. Therefore, CYP450 substrates with a narrow therapeutic indie, such as warfarin, may have fluctuations in drug levels and therapeutic effect when brodalumab therapy is started or discontinued. This effect on CYP450 enzyme activity may persist for several weeks after stopping brodalumab.
Yellow Fever Vaccine, Live: (Major) Avoid administration of live vaccines to brodalumab recipients. Before initiation of brodalumab therapy, consider completion of all age appropriate vaccinations per current immunization guidelines. No data are available on the response to live or inactive vaccines in patients receiving brodalumab therapy.
Brodalumab is a human IgG2 monoclonal antibody that selectively binds to human interleukin-17 receptor A (IL-17RA). Human IL-17RA is a protein expressed on cell surfaces and is a required component of receptor complexes utilized by multiple IL-17 family cytokines. By binding to IL-17RA, brodalumab inhibits the receptors interaction with cytokines IL-17A, IL-17F, IL-17C, IL-17A/F heterodimer, and IL-25; thereby preventing IL-17 cytokine-induced release of proinflammatory cytokines and chemokines.
Brodalumab is administered subcutaneously.
The mean volume of distribution following a single subcutaneous dose in patients with plaque psoriasis was 8.9 +/- 9.4 L. Although the metabolic pathway has not been characterized, brodalumab is expected to be degraded to small peptides and amino acids via catabolic pathways in the same manner as endogenous human IgG. The drug exhibits nonlinear elimination, with clearance increasing as the dose decreases; the mean total clearance after a single 210 mg subcutaneous dose is 3 +/- 3.5 L/day.
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters:
The formation of CYP450 enzymes can be altered by increased concentrations of certain cytokines during chronic inflammation. Theoretically, brodalumab, could normalize the formation of CYP450 enzymes.
-Route-Specific Pharmacokinetics
Subcutaneous Route
Brodalumab bioavailability is approximately 55% following subcutaneous administration in patients with plaque psoriasis. After a single 210 mg dose, peak serum concentrations (Cmax) of 13.4 +/- 7.3 mcg/mL are reached approximately 3 days post dose. Mean exposure (AUC) after a single dose is 111 +/- 64 mcg x day/mL. Steady-state is achieved by week 4, with mean Cmax and AUC of 20.6 +/- 14.6 mcg/mL and 227 +/- 167 mcg x day/mL, respectively. The drug exhibits nonlinear pharmacokinetics with exposures increasing in a greater than dose-proportional manner over a dose range from 140 mg (0.67-times recommended dose) to 350 mg (1.67-times recommended dose).
-Special Populations
Obesity
Trough concentrations (Cmin) of brodalumab are lower in subjects with higher body weight.