TALTZ

Antipsoriatic Monoclonal Antibodies and Others
Interleukin-17A (IL-17A) Inhibitors

Administer by subcutaneous injection only.
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, and colorless to slightly yellow.

Ixekizumab is available as a prefilled syringe and as an autoinjector. Each device contains 80 mg ixekizumab.
The product is intended for use under the guidance and supervision of a physician
Adults may self-inject or caregivers may give subcutaneous injections after proper training.
Caregivers may give injections of the 80 mg dose to pediatric patients weighing more than 50 kg using the autoinjector or prefilled syringe after training and demonstration of proper subcutaneous injection technique.
Pediatric doses of 20 mg or 40 mg must be prepared and administered by a qualified healthcare professional.
Each 160 mg dose is administered as 2 subcutaneous injections of 80 mg.
Administration sites for patient administration include upper arms, thighs, and any quadrant of the abdomen. Healthcare professionals may inject in the upper, outer arm.
Do not administer where the skin is tender, bruised, erythematous, indurated or affected by psoriasis.
Rotate sites of injection with each dose. Injections should be administered at a different location than was used for the previous injection.
Wash hands with soap and water before drug administration. Clean injection site with an alcohol wipe and let dry.
Ixekizumab does not contain preservatives; therefore, discard any unused product remaining in the prefilled syringe or autoinjector. Discard the single-dose autoinjector or syringe after use in a proper puncture-resistant container.
Missed doses: If a dose or administration time is missed, administer the missed dose as soon as possible. Thereafter, resume dosing at the regularly scheduled time.[60658]
 
Preparation for the use of the 80 mg/mL prefilled syringe or autoinjector:
Remove prefilled syringe or autoinjector from the refrigerator and allow 30 minutes to reach room temperature. DO NOT use any methods to speed the warming process, such as a microwave, hot water, or sunlight.
Inspect syringe or autoinjector for particulate matter and discoloration prior to administration. The autoinjector contains glass parts; do not use the autoinjector if it is dropped on a hard surface.
Storage of unopened prefilled-syringes and autoinjectors: Protect from light and store refrigerated at 2 to 8 degrees C (36 to 46 degrees F) until time of use. Do not freeze and do not use the injection if it has been frozen. Do not shake.
If needed, a prefilled-syringe or autoinjector may be stored at room temperature up to 30 degrees C (86 degrees F) for up to 5 days in the original carton to protect from light. Once the product has been stored at room temperature, do not return to the refrigerator and discard, if unused, within 5 days.
Record the date when first removed from the refrigerator in the spaces provided on the carton.
For the 2 or 3 autoinjector pack, remove a single autoinjector at the time, leaving the remaining autoinjector(s) in the original carton in the refrigerator. Ensure the unrefrigerated autoinjector is protected from light.[60658]
 
Preparation of the 20 mg and 40 mg pediatric doses using the 80 mg/mL prefilled syringe:
Must be prepared and administered by a qualified healthcare professional.
Gather the following supplies:
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. DO NOT add any other medication to the vial.
Using the 0.5 mL or 1 mL disposable syringe and sterile needle, withdraw the prescribed dose from the vial (i.e., 0.25 mL for 20 mg dose; 0.5 mL for 40 mg dose).
Remove the needle from the syringe and replace it with a 27-gauge needle prior to administration to the patient.
Storage of prepared 20 mg or 40 mg pediatric dose: If necessary, the prepared dose may be stored at room temperature for up to 4 hours from first puncturing the sterile vial.[60658]
 
Autoinjector:
If you have vision or hearing problems, do not use autoinjector without help from a caregiver.
Make sure the lock ring is in the lock position, and leave the base cap on until you are ready to inject. Do not touch the needle.
Twist off the base cap in the direction of the arrows and throw it in the trash. Do not put the cap back on once it has been removed from the autoinjector.
Place the clear base flat and firmly against your skin at the injection site. Turn the lock ring to the unlock position.
Press the green injection button. There will be a loud click. Keep holding the clear base firmly against your skin. You will hear a 2nd click in about 10 seconds to indicate the injection is complete. You will see the gray plunger at the top of the clear base.
Remove the autoinjector from your skin.[60658]
 
Prefilled syringe:
If you have vision problems, do not use the prefilled syringe without help from a caregiver.
Pull the needle cap off and throw it away. Do not put the cap back on once it has been removed from the autoinjector. Do not touch the needle.
Gently pinch and hold a fold of skin where you will inject.
Insert the needle at a 45-degree angle. Then let go of your skin before you push the plunger. Make sure to keep the needle in place.
Slowly push the thumb pad to push the plunger all the way in until all the medicine is injected. You should see the green plunger rod show through the syringe body when the injection is complete.
Remove the needle from the skin.[60658]

angioedema / Rapid / 0-0.1
anaphylactoid reactions / Rapid / Incidence not known

antibody formation / Delayed / 1.5-22.0
neutropenia / Delayed / 11.0-11.0
conjunctivitis / Delayed / 0-2.6
ocular infection / Delayed / 0-1.3
candidiasis / Delayed / 0-1.0
inflammatory bowel disease / Delayed / 0.1-1.0
thrombocytopenia / Delayed / Incidence not known

infection / Delayed / 27.0-27.0
injection site reaction / Rapid / 14.0-14.0
nausea / Early / 2.0-2.0
urticaria / Rapid / 0-1.7
influenza / Delayed / 0-1.7
rhinitis / Early / 0-1.0
pharyngitis / Delayed / Incidence not known

TALTZ

Rx

Subcutaneous humanized IgG4 monoclonal antibody that selectively targets interleukin-17A (IL-17A)
Used to treat moderate to severe plaque psoriasis in patients 6 years and older, used in adults for psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis
As with other interleukin inhibitors, may increase risk of infection

160 mg subcutaneously at week 0, then 80 mg subcutaneously at weeks 2, 4, 6, 8, 10, and 12, and then 80 mg subcutaneously every 4 weeks. May increase the maintenance dose to 80 mg subcutaneously every 2 weeks if an inadequate primary response may be due to insufficient drug exposure (e.g., known subtherapeutic drug concentrations, obesity, relapse during treatment); however, consider the increased risk for infection and adverse reactions.

160 mg subcutaneously at week 0, then 80 mg subcutaneously every 4 weeks.[60658]

80 mg subcutaneously at week 0, then 40 mg subcutaneously every 4 weeks.

40 mg subcutaneously at week 0, then 20 mg subcutaneously every 4 weeks.

160 mg subcutaneously at week 0, then 80 mg subcutaneously every 4 weeks. May be administered alone or in combination with a conventional disease-modifying antirheumatic drug (DMARD).

160 mg subcutaneously at week 0, then 80 mg subcutaneously at weeks 2, 4, 6, 8, 10, and 12, and then 80 mg subcutaneously every 4 weeks. May be administered alone or in combination with a conventional disease-modifying antirheumatic drug (DMARD).

160 mg subcutaneously at week 0 (administered as two 80-mg injections) followed by 80 mg subcutaneously every 4 weeks. May be administered with conventional disease modifying antirheumatic drugs (DMARDs), corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), or analgesics.[60658]

80 mg subcutaneously every 4 weeks. May be administered with conventional disease modifying antirheumatic drugs (DMARDs), corticosteroids, nonsteroidal anti-inflammatory drugs (NSAIDs), or analgesics.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears no dosage adjustments are needed.

Abatacept: (Major) Concomitant use of abatacept with other biologic agents, such as ixekizumab, 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 ixekizumab.
Bacillus Calmette-Guerin Vaccine, BCG: (Major) Do not administer live vaccines to ixekizumab recipients. Before initiation of ixekizumab 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 Ixekizumab therapy.
Canakinumab: (Major) Avoid the concomitant use of canakinumab with other interleukin inhibitors, such as ixekizumab; coadministration has not been studied and may result in additive immunosuppression and increased risk of infection.
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.
Intranasal Influenza Vaccine: (Major) Do not administer live vaccines to ixekizumab recipients. Before initiation of ixekizumab 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 Ixekizumab therapy.
Live Vaccines: (Major) Do not administer live vaccines to ixekizumab recipients. Before initiation of ixekizumab 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 Ixekizumab therapy.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) Do not administer live vaccines to ixekizumab recipients. Before initiation of ixekizumab 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 Ixekizumab therapy.
Measles/Mumps/Rubella Vaccines, MMR: (Major) Do not administer live vaccines to ixekizumab recipients. Before initiation of ixekizumab 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 Ixekizumab therapy.
Rotavirus Vaccine: (Major) Do not administer live vaccines to ixekizumab recipients. Before initiation of ixekizumab 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 Ixekizumab 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.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Major) Do not administer live vaccines to ixekizumab recipients. Before initiation of ixekizumab 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 Ixekizumab therapy.
Smallpox Vaccine, Vaccinia Vaccine: (Major) Do not administer live vaccines to ixekizumab recipients. Before initiation of ixekizumab 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 Ixekizumab therapy.
Tofacitinib: (Major) Concomitant use of tofacitinib with biologic immunosuppressants, such as ixekizumab, 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 ixekizumab recipients. Before initiation of ixekizumab 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 Ixekizumab therapy.
Upadacitinib: (Major) Do not use upadacitinib in combination with biologic immunosuppressives, such as ixekizumab, 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) Do not administer live vaccines to ixekizumab recipients. Before initiation of ixekizumab 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 Ixekizumab therapy.
Yellow Fever Vaccine, Live: (Major) Do not administer live vaccines to ixekizumab recipients. Before initiation of ixekizumab 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 Ixekizumab therapy.

TALTZ Subcutaneous Inj Sol: 1mL, 80mg

160 mg/dose subcutaneously initially, then 80 mg/dose subcutaneously for maintenance therapy for psoriasis, psoriatic arthritis, and ankylosing spondyloarthritis; for non-radiographic axial spondyloarthritis 80 mg/dose subcutaneously.

160 mg/dose subcutaneously initially, then 80 mg/dose subcutaneously for maintenance therapy for psoriasis, psoriatic arthritis, and ankylosing spondyloarthritis; for non-radiographic axial spondyloarthritis 80 mg/dose subcutaneously.

more than 50 kg: 160 mg/dose subcutaneously initially, then 80 mg/dose subcutaneously for maintenance therapy of plaque psoriasis; safety and efficacy have not been established for psoriatic arthritis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis.
25 to 50 kg: 80 mg/dose subcutaneously initially, then 40 mg/dose subcutaneously for maintenance therapy of plaque psoriasis; safety and efficacy have not been established for psoriatic arthritis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis.
less than 25 kg: 40 mg/dose subcutaneously initially, then 20 mg/dose subcutaneously for maintenance therapy of plaque psoriasis; safety and efficacy have not been established for psoriatic arthritis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis.

6 years or older and more than 50 kg: 160 mg/dose subcutaneously initially, then 80 mg/dose subcutaneously for maintenance therapy of plaque psoriasis; safety and efficacy have not been established for psoriatic arthritis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis.
6 years or older and 25 to 50 kg: 80 mg/dose subcutaneously initially, then 40 mg/dose subcutaneously for maintenance therapy of plaque psoriasis; safety and efficacy have not been established for psoriatic arthritis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis.
6 years or older and less than 25 kg: 40 mg/dose subcutaneously initially, then 20 mg/dose subcutaneously for maintenance therapy of plaque psoriasis; safety and efficacy have not been established for psoriatic arthritis, ankylosing spondylitis, or non-radiographic axial spondyloarthritis.
1 to 5 years: Safety and efficacy have not been established.

Not indicated.

Not indicated.

Ixekizumab is a human IgG4 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. Treatment with ixekizumab inhibits the release of proinflammatory cytokines and chemokines.

Ixekizumab is administered subcutaneously. The mean volume of distribution in patients with plaque psoriasis is 7.11 L (29%). Although the metabolic pathway is not fully elucidated, ixekizumab is expected to be degraded to small peptides and amino acids via catabolic pathways in the same manner as endogenous human IgG. Mean systemic clearance is 0.39 L/day, and the mean half-life is 13 days. Ixekizumab exhibits dose-proportional pharmacokinetics in patients with plaque psoriasis over a dose range from 5 mg (not recommended) to 160 mg following subcutaneous administration. The pharmacokinetics of ixekizumab was similar in adult patients with plaque psoriasis, psoriatic arthritis, ankylosing spondylitis, and non-radiographic axial spondyloarthritis.
 
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: CYP2D6
Data from drug interaction studies found no clinical significant changes in the exposure of caffeine (CYP1A2 substrate), warfarin (CYP2C9 substrate), omeprazole (CYP2C19 substrate), or midazolam (CYP3A substrate) when used concurrently with ixekizumab as a single 160 mg dose or multiple doses of 80 mg every 2 weeks. The potential effect of ixekizumab on CYP2D6 activity cannot be ruled out due to high variability in exposure (approximately +/- 2-fold) of dextromethorphan and its CYP2D6 metabolite dextrorphan.

Ixekizumab bioavailability ranges from 60% to 81% following subcutaneous administration in patients with plaque psoriasis. Administration via injection in the thigh achieved higher bioavailability compared to that seen with other injection sites including the arm and abdomen. The peak mean (+/- SD) serum concentration of ixekizumab after a subcutaneous doses of 160 mg is 16.2 +/- 6.6 mcg/mL and is reached in approximately 4 days. Following multiple subcutaneous doses of 160 mg ixekizumab, the mean (+/- SD) serum trough concentration at week 8 is 9.3 +/- 5.3 mcg/mL. Steady-state concentrations are achieved by week 10 after switching from the 80 mg every 2 weeks regimen to the 80 mg every 4 weeks dosing regimen at week 12 at which the mean (+/- SD) steady state trough concentration is 3.5 +/- 2.5 mcg/mL.

Available data regarding the use of ixekizumab during pregnancy are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriages, or other adverse maternal or fetal outcomes. Human IgG does cross the placental barrier; therefore, ixekizumab may be transmitted from mother to fetus. No effects on neonatal development were observed when monkeys were given ixekizumab at dose exposures up to 19-times the maximum recommended human dose (MRHD). When dosing was continued until parturition, neonatal deaths, attributed to early delivery, trauma, or congenital defect, were observed at 1.9-times the MRHD. The clinical significance of these findings is unknown. There is a pregnancy exposure registry that monitors outcomes in pregnant patients exposed to ixekizumab; pregnant patients are encouraged to enroll themselves by calling 1-800-284-1695.

There are no available data on the presence of ixekizumab in human milk, the effects on breast-fed infants, 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 it will also be present in human milk. Consider the benefits of breast-feeding along with the mother's clinical need for ixekizumab and any potential adverse effects on the breast-fed infant from ixekizumab 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.