Tildrakizumab is an interleukin-23 antagonist indicated for the treatment of adults with moderate to severe plaque psoriasis who are candidates for systemic therapy or phototherapy. The drug should only be given subcutaneously by a qualified health professional. Prior to administration, all potential drug recipients must be evaluated for tuberculosis (TB) infections. DO NOT administer tildrakizumab to patients with active TB infection; patients with latent TB should initiate treatment before receiving tildrakizumab.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Injectable Administration
-Prior to administration, remove the carton from refrigerator and let the prefilled syringe (in the carton with the lid closed) sit at room temperature for 30 minutes. Do not use other methods to speed the warming process.
-Once brought to room temperature, do not place back into the refrigerator. If needed, the prefilled syringe may be stored at room temperature for up to 30 days. Any prefilled syringe that has been stored at room temperature for more than 30 days or at temperatures greater than 25 degrees C (77 degrees F) MUST be discarded.
-DO NOT shake the prefilled syringe.
-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. Do not use if the solution is discolored or contains visible particles. Do not use if syringe is damaged.
Subcutaneous Administration
-The injection should only be administered by a qualified healthcare professional.
-Choose an injection site with clear skin and easy access, such as abdomen, thighs, or upper arm. Do not administer within 2 inches of the navel or where the skin is tender, bruised, erythematous, indurated, or affected by psoriasis. Do not inject into scars, stretch marks, or blood vessels.
-Clean injection site with alcohol wipe and allow site to dry.
-While holding the body of the syringe, pull the needle cover straight off (DO NOT twist). Do not pull off the needle cover until ready to inject. Discard the needle cover.
-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 while inserting the needle.
-Using slow and constant pressure, push the blue plunger all the way down until it can go no further. This activates the safety mechanism that will ensure full retraction of the needle after the injection is given.
-Remove the needle from the skin entirely before letting go of the blue plunger. After the blue plunger is released, the safety lock will draw the needle inside the needle guard.
-Discard any unused portion. Discard the used syringe.
Although 23% of tildrakizumab recipients developed an infection during clinical trials, the difference in infection frequency between the treatment group and placebo group (22%) was less than 1%. The majority of these infections were mild to moderate in severity, with 0.3% or less being considered serious infections. The most commonly reported infections (14%) were upper respiratory tract infections, which consisted of pharyngitis, nasopharyngitis, and viral respiratory infections. 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 tildrakizumab until the infection resolves and monitor the patient closely.
An injection site reaction was observed in 3% of patients treated with tildrakizumab during clinical trials. Specific reactions occurring at the injection site included pruritus, pain, erythema, inflammation, edema, swelling, bruising, hematoma, and bleeding.
Diarrhea was reported in 2% of patients receiving tildrakizumab and 1% of patients receiving placebo during clinical trials.
Cases of angioedema and urticaria were reported in tildrakizumab treated patients during clinical trials. If a serious hypersensitivity reaction occurs, discontinue tildrakizumab immediately and initiate appropriate therapy.
The development of immunogenicity (antibody formation) may occur with the use of tildrakizumab. During the 64-week treatment period approximately 6.5% of patients developed antibodies to the tildrakizumab. Of those subjects who developed antibodies to the drug, approximately 40% (2.5% of all tildrakizumab recipients) were classified as neutralizing (i.e., associated with reduced drug concentration and loss of efficacy). However, the detection of antibodies is dependent on the sensitivity and specificity of the assay. In addition, 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 tildrakizumab cannot be directly compared to other products.
Avoid vaccination of tildrakizumab 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 tildrakizumab. Consider completing all age appropriate immunizations prior to initiating tildrakizumab therapy.
Tildrakizumab 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 tildrakizumab therapy. 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 tildrakizumab until the infection resolves and monitor the patient closely.
Evaluate all patients for tuberculosis before initiating tildrakizumab 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 tildrakizumab. Use of antituberculosis therapy before tildrakizumab 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 tildrakizumab. 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.
There are limited data on the use of tildrakizumab during pregnancy and drug-related fetal risks are not known. Human IgG does cross the placental barrier; therefore, tildrakizumab may be transferred from mother to fetus. No effects on neonatal development were observed when pregnant monkeys were administered the drug during organogenesis to near parturition at dose up to 159-times the maximum recommended human dose (MRHD). However, when the dosing was continued until parturition, a small increase in neonatal death was observed with doses at 59-times the MRHD. The clinical significance of this finding is unknown. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to tildrakizumab; information about the registry can be obtained at mothertobaby.org/ongoing-study/ilumya or by calling 1-877-311-8972.
There are no data on the presence of tildrakizumab 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 tildrakizumab. 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 tildrakizumab, 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 tildrakizumab, 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 phytotherapy:
Subcutaneous dosage:
Adults: 100 mg subcutaneously at weeks 0 and 4, then 100 mg subcutaneously every 12 weeks. May increase the dose to 200 mg subcutaneously every 12 weeks if an inadequate primary response may be due to insufficient drug exposure in persons weighing 90 kg or more or with a high disease burden; however, consider the increased risk for infection and adverse reactions.
Maximum Dosage Limits:
-Adults
100 mg/dose subcutaneously; maintenance therapy every 12 weeks.
-Geriatric
100 mg/dose subcutaneously; maintenance therapy every 12 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 tildrakizumab recipients. Before initiation of tildrakizumab 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 tildrakizumab therapy.
Canakinumab: (Major) Avoid the concomitant use of canakinumab with other interleukin inhibitors, such as tildrakizumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
Chikungunya Vaccine, Live: (Major) Avoid administration of live vaccines to tildrakizumab recipients. Before initiation of tildrakizumab 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 tildrakizumab therapy.
Intranasal Influenza Vaccine: (Major) Avoid administration of live vaccines to tildrakizumab recipients. Before initiation of tildrakizumab 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 tildrakizumab therapy.
Live Vaccines: (Major) Avoid administration of live vaccines to tildrakizumab recipients. Before initiation of tildrakizumab 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 tildrakizumab therapy.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) Avoid administration of live vaccines to tildrakizumab recipients. Before initiation of tildrakizumab 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 tildrakizumab therapy.
Measles/Mumps/Rubella Vaccines, MMR: (Major) Avoid administration of live vaccines to tildrakizumab recipients. Before initiation of tildrakizumab 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 tildrakizumab therapy.
Rotavirus Vaccine: (Major) Avoid administration of live vaccines to tildrakizumab recipients. Before initiation of tildrakizumab 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 tildrakizumab therapy.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Major) Avoid administration of live vaccines to tildrakizumab recipients. Before initiation of tildrakizumab 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 tildrakizumab therapy.
Smallpox Vaccine, Vaccinia Vaccine: (Major) Avoid administration of live vaccines to tildrakizumab recipients. Before initiation of tildrakizumab 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 tildrakizumab therapy.
Typhoid Vaccine: (Major) Avoid administration of live vaccines to tildrakizumab recipients. Before initiation of tildrakizumab 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 tildrakizumab therapy.
Varicella-Zoster Virus Vaccine, Live: (Major) Avoid administration of live vaccines to tildrakizumab recipients. Before initiation of tildrakizumab 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 tildrakizumab therapy.
Yellow Fever Vaccine, Live: (Major) Avoid administration of live vaccines to tildrakizumab recipients. Before initiation of tildrakizumab 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 tildrakizumab therapy.
Tildrakizumab is a humanized IgG1/k monoclonal antibody that selectively binds to the p19 subunit of human interleukin-23 (IL-23), thereby inhibiting its interaction with the IL-23 receptor. Human IL-23 is a naturally occurring cytokine involved in inflammatory and immune responses. By blocking IL-23 from binding to it's receptor, tildrakizumab prevents the release of proinflammatory cytokines and chemokines.
Tildrakizumab is administered subcutaneously. Once in systemic circulation, the mean volume of distribution is 10.8 L. Although the metabolic pathway has not been characterized, tildrakizumab 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 a mean systemic clearance of 0.32 L/day and has a half-life of approximately 23 days.
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP2D6
In a drug interaction study, systemic exposure of dextromethorphan (a CYP2D6 substrate) increased by 20% when given concurrently with 200 mg of tildrakizumab (i.e., 2-times the recommended dose). However, administration of tildrakizumab with substrates of CYP1A2, CYP2C9, CYP2C19, and CYP3A4 did not result in any clinically significant changes in the exposure of these substrates.
-Route-Specific Pharmacokinetics
Subcutaneous Route
The absolute bioavailability of subcutaneously administered tildrakizumab is estimated to be between 73% and 80%, with peak serum concentrations (Cmax) being reached approximately 6 days post dose. Steady-state concentrations are achieved by week 16 when tildrakizumab is administered using the recommended dosing schedule (i.e., weeks 0, 4, 12). The drug exhibits linear pharmacokinetics with exposures increasing proportionally over a dose range from 50 mg (0.5-times recommended dose) to 200 mg (2-times recommended dose). The recommended 100 mg dose produces a mean steady-state trough concentration that ranging from 1.22 +/- 0.94 mcg/mL to 1.47 +/- 1.12 mcg/mL, and a geometric mean Cmax of 8.1 mcg/mL.
-Special Populations
Obesity
Concentrations of tildrakizumab are lower in subjects with higher body weight.