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TALTZ (ixekizumab) injection

Ixekizumab is a humanized immunoglobulin G subclass 4 (IgG4) monoclonal antibody (mAb) with neutralizing activity against IL-17A. Ixekizumab is produced by recombinant DNA technology in a recombinant mammalian cell line and purified using standard technology for bioprocessing. Ixekizumab is comprised of two identical light chain polypeptides of 219 amino acids each and two identical heavy chain polypeptides of 445 amino acids each, and has a molecular weight of 146,158 Daltons for the protein backbone of the molecule.

TALTZ injection is a sterile, preservative free, clear and colorless to slightly yellow solution, for subcutaneous use available as 80 mg of ixekizumab in a 1 mL single-dose prefilled autoinjector or a single-dose prefilled syringe. The prefilled autoinjector and prefilled syringe each contain a 1 mL glass syringe with a fixed 27 gauge ½ inch needle. The TALTZ 80 mg prefilled autoinjector and prefilled syringe are manufactured to deliver 80 mg of ixekizumab.

Each mL is composed of ixekizumab (80 mg); Polysorbate 80, USP (0.3 mg); Sucrose, USP (80 mg); and Water for Injection, USP. Sodium Hydroxide, USP-NF, may have been added to adjust pH. The TALTZ solution has a pH of 5.2 – 6.2.

INDICATIONS AND USAGE

Plaque Psoriasis: TALTZ® is indicated for the treatment of patients 6 years of age and older with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

Psoriatic Arthritis: TALTZ is indicated for the treatment of adult patients with active psoriatic arthritis.

Ankylosing Spondylitis: TALTZ is indicated for the treatment of adult patients with active ankylosing spondylitis.

Non-radiographic Axial Spondyloarthritis: TALTZ is indicated for the treatment of adult patients with active non-radiographic axial spondyloarthritis (nraxSpA) with objective signs of inflammation.

Mechanism of Action

Ixekizumab is a humanized IgG4 monoclonal antibody that selectively binds with the interleukin 17A (IL-17A) cytokine and inhibits its interaction with the IL-17 receptor. IL-17A is a naturally occurring cytokine that is involved in normal inflammatory and immune responses. Ixekizumab inhibits the release of proinflammatory cytokines and chemokines.

DOSAGE AND ADMINISTRATION

Testing and Procedures Prior to Treatment Initiation

Evaluate patients for tuberculosis (TB) infection. TALTZ initiation is not recommended in patients with active TB infection. Initiate treatment of latent TB prior to initiation of TALTZ.

Complete all age-appropriate vaccinations as recommended by current immunization guidelines prior to initiating treatment with TALTZ.

Adult Plaque Psoriasis: TALTZ is administered by subcutaneous injection. The recommended dosage is 160 mg (two 80 mg injections) at Week 0, followed by 80 mg at Weeks 2, 4, 6, 8, 10, and 12, then 80 mg every 4 weeks.

Pediatric Plaque Psoriasis: TALTZ is administered by subcutaneous injection every 4 weeks (Q4W). The recommended dosage in pediatric patients from 6 to less than 18 years of age with moderate-to-severe plaque psoriasis is based on the following weight categories.

Greater than 50 kg: Starting Dose (Week 0), 160 mg (two 80 mg injections). Dose every 4 weeks (Q4W) Thereafter, 80 mg.
25 to 50 kg: Starting Dose (Week 0), 80 mg. Dose every 4 weeks (Q4W) Thereafter, 40 mg.
Less than 25 kg: Starting Dose (Week 0), 40 mg. Dose every 4 weeks (Q4W) Thereafter, 20 mg.

Psoriatic Arthritis: The recommended dosage is 160 mg by subcutaneous injection (two 80 mg injections) at Week 0, followed by 80 mg every 4 weeks.

For psoriatic arthritis patients with coexistent moderate-to-severe plaque psoriasis, use the dosing regimen for adult plaque psoriasis.

TALTZ may be administered alone or in combination with a conventional disease-modifying antirheumatic drug (cDMARD) (e.g., methotrexate).

Ankylosing Spondylitis: The recommended dosage is 160 mg by subcutaneous injection (two 80 mg injections) at Week 0, followed by 80 mg every 4 weeks.

Non-radiographic Axial Spondyloarthritis: The recommended dosage is 80 mg by subcutaneous injection every 4 weeks.

Important Administration Instructions

TALTZ is intended for use under the guidance and supervision of a physician. Adult patients may self-inject or caregivers may give injections of TALTZ 80 mg after training in subcutaneous injection technique using the autoinjector or prefilled syringe. Caregivers may give injections of TALTZ 80 mg to pediatric patients weighing more than 50 kg using the autoinjector or prefilled syringe after training and demonstration of proper subcutaneous injection technique.

The TALTZ “Instructions for Use” contains more detailed instructions on the preparation and administrati on of TALTZ.

Before injection, remove TALTZ autoinjector or TALTZ prefilled syringe from the refrigerator and allow TALTZ to reach room temperature (30 minutes) without removing the needle cap. Inspect TALTZ visually for particulate matter and discoloration prior to administration. TALTZ is a clear and colorless to slightly yellow solution. Do not use if the liquid contains visible particles, is discolored or cloudy (other than clear and colorless to slightly yellow).

Administer each injection at a different anatomic location (such as upper arms, thighs or any quadrant of abdomen) than the previous injection, and not into areas where the skin is tender, bruised, erythematous, indurated or affected by psoriasis. Administration of TALTZ in the upper, outer arm may be performed by a caregiver or healthcare provider.

TALTZ does not contain preservatives, therefore discard any unused product.

If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.

Pediatric Patients Weighing 50 kg or Less

TALTZ doses of 20 mg or 40 mg must be prepared and administered by a qualified healthcare professional. Use only the commercial TALTZ 80 mg/1 mL prefilled syringe when preparing the prescribed 20 mg and 40 mg pediatric dose [see Instructions for Use].

Gather the following necessary supplies for preparation:

0.5 mL or 1 mL disposable syringe
Sterile needle for withdrawal
27-gauge sterile needle for administration
Sterile, clear glass vial.

Expel the entire contents of the prefilled syringe into the sterile vial. DO NOT shake or swirl the vial. No other medications should be added to solutions containing TALTZ.

Using the 0.5 mL or 1 mL disposable syringe and sterile needle, withdraw the prescribed dose from the vial (0.25 mL for 20 mg; 0.5 mL for 40 mg).

Remove the needle from the syringe and replace it with a 27-gauge needle prior to administering TALTZ to the patient.

Storage: If necessary, the prepared TALTZ may be stored at room temperature for up to 4 hours from first puncturing the sterile vial.

CONTRAINDICATIONS

TALTZ is contraindicated in patients with a previous serious hypersensitivity reaction, such as anaphylaxis, to ixekizumab or to any of the excipients.

WARNINGS AND PRECAUTIONS

Infections: TALTZ may increase the risk of infection. In clinical trials in adult patients with plaque psoriasis, the TALTZ group had a higher rate of infections than the placebo group (27% vs. 23%). Upper respiratory tract infections, oral candidiasis, conjunctivitis and tinea infections occurred more frequently in the TALTZ group than in the placebo group. A similar increase in risk of infection was seen in placebo-controlled trials in patients with pediatric psoriasis, psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis.

Instruct patients treated with TALTZ to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a serious infection or is not responding to standard therapy, monitor the patient closely and discontinue TALTZ until the infection resolves.

Pre-treatment Evaluation for Tuberculosis: Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with TALTZ. Do not administer to patients with active TB infection. Initiate treatment of latent TB prior to administering TALTZ. Consider anti-TB therapy prior to initiating TALTZ in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving TALTZ should be monitored closely for signs and symptoms of active TB during and after treatment.

Hypersensitivity: Serious hypersensitivity reactions, including angioedema and urticaria (each ≤0.1%), occurred in the TALTZ group in clinical trials. Anaphylaxis, including cases leading to hospitalization, has been reported in post marketing use with TALTZ. If a serious hypersensitivity reaction occurs, discontinue TALTZ immediately and initiate appropriate therapy.

Inflammatory Bowel Disease: Patients treated with TALTZ may be at increased risk of inflammatory bowel disease. In clinical trials, Crohn’s disease and ulcerative colitis, including exacerbations, occurred at a greater frequency in the TALTZ group than the placebo control group. During TALTZ treatment, monitor for onset or exacerbation of inflammatory bowel disease and if IBD occurs, discontinue TALTZ and initiate appropriate medical management.

Immunizations: Prior to initiating therapy with TALTZ, consider completion of all age-appropriate immunizations according to current immunization guidelines. Avoid use of live vaccines in patients treated with TALTZ. No data are available on the response to live vaccines.

USE IN SPECIFIC POPULATIONS

Pregnancy: Available data from the published literature and the pharmacovigilance database with TALTZ use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage or other adverse maternal or fetal outcomes.

Human IgG is known to cross the placental barrier; therefore, TALTZ may be transmitted from the mother to the developing fetus. An embryofetal development study conducted in pregnant monkeys during organogenesis at doses up to 19 times the maximum recommended human dose (MRHD) revealed no evidence of harm to the developing fetus.

When dosing was continued until parturition, neonatal deaths were observed at 1.9 times the MRHD. The clinical significance of these nonclinical findings is unknown.

Lactation: There are no available data on the presence of ixekizumab in human milk, the effects on the breastfed infant, or the effects on milk production. Ixekizumab was detected in the milk of lactating cynomolgus monkeys. When a drug is present in animal milk, it is likely that the drug will be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for TALTZ and any potential adverse effects on the breastfed infant from TALTZ or from the underlying maternal condition.

Pediatric Use: The safety and effectiveness of TALTZ have been established in pediatric subjects aged 6 years to less than 18 years with moderate-to-severe plaque psoriasis. The safety and effectiveness of TALTZ in other pediatric indications and for pediatric subjects less than 6 years of age have not been established.

Geriatric Use: Of the 4204 adult psoriasis subjects exposed to TALTZ, a total of 301 were 65 years or older, and 36 subjects were 75 years or older. Although no differences in safety or efficacy were observed between older and younger subjects, the number of subjects aged 65 and over is not sufficient to determine whether they respond differently from younger subjects

TALTZ (ixekizumab) injection

TALTZ (ixekizumab) injection