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  • CLASSES

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

    DEA CLASS

    Rx

    DESCRIPTION

    Humanized IgG4 monoclonal antibody that selectively targets the interleukin-17A (IL-17A) cytokine, inhibiting its action
    Approved for moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy
    Also approved for psoriatic arthritis (PsA) in adults

    COMMON BRAND NAMES

    TALTZ

    HOW SUPPLIED

    TALTZ Subcutaneous Inj Sol: 1mL, 80mg

    DOSAGE & INDICATIONS

    For the treatment of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.
    Subcutaneous dosage
    Adults

    160 mg subcutaneously at week 0 (administered as two 80-mg injections) followed by 80 mg subcutaneously at weeks 2, 4, 6, 8, 10, and 12, then 80 mg subcutaneously every 4 weeks.

    For the treatment of active psoriatic arthritis (PsA).
    Subcutaneous dosage
    Adults

    160 mg subcutaneously at week 0 (administered as two 80-mg injections) followed by 80 mg subcutaneously every 4 weeks. If patients also have coexistent moderate-to-severe plaque psoriasis, use the dosing regimen for plaque psoriasis. May be administered alone or in combination with a conventional disease-modifying antirheumatic drug (DMARD).

    MAXIMUM DOSAGE

    Adults

    160 mg/dose subcutaneously initially, then 80 mg/dose subcutaneously for maintenance therapy.

    Geriatric

    160 mg/dose subcutaneously initially, then 80 mg/dose subcutaneously for maintenance therapy.

    Adolescents

    Safety and efficacy have not been established.

    Children

    Safety and efficacy have not been established.

    Infants

    Not indicated.

    Neonates

    Not indicated.

    DOSING CONSIDERATIONS

    Hepatic Impairment

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

    Renal Impairment

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

    ADMINISTRATION

    Injectable Administration

    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.

    Subcutaneous Administration

    Ixekizumab is available as a prefilled syringe and as an autoinjector. Each device contains 80 mg ixekizumab.
    Patients may use the prefilled syringe or autoinjector after proper training.
    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 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 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 regular scheduled time.
     
     
    Preparation for use of the prefilled syringe or autoinjector:
    Remove prefilled syringe or autoinjector from refrigerator and allow 30 minutes to reach room temperature. DO NOT use any methods to speed the heating 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 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.
     
    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 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.
     
    Prefilled syringe:
    If you have vision problems, do not use 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.

    STORAGE

    TALTZ :
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Discard unused portion. Do not store for later use.
    - Do not freeze
    - Do not use if product has been frozen
    - Protect from light
    - Refrigerated product should reach room temperature before administration
    - Store between 36 to 46 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    Risk of serious hypersensitivity reactions or anaphylaxis

    Ixekizumab is contraindicated in patients with a previous serious hypersensitivity reaction, such as anaphylaxis, to ixekizumab or to any of the product excipients. Ixekizumab is associated with a risk of serious hypersensitivity reactions or anaphylaxis; angioedema and urticaria occurred in the ixekizumab group in clinical trials. In addition, anaphylaxis, including cases resulting in hospitalization, has been reported during postmarketing use. If an anaphylactic or other clinically significant hypersensitivity reaction occurs, institute appropriate therapy and immediately discontinue ixekizumab. Patients should not inject additional doses if a serious hypersensitivity reaction occurs.

    Immunosuppression, infection

    Ixekizumab may increase the risk of infection and may increase the risk for reactivation of latent infections, due to its effects on the immune system. In clinical trials, a higher rate of infections was reported with ixekizumab compared to placebo. Serious bacterial, fungal, and viral infections may occur. Do not initiate ixekizumab until any clinically important active infection in a patient resolves or is adequately treated. In clinical trials, a higher rate of infections was reported with ixekizumab compared to placebo. Instruct patients to seek medical advice if signs or symptoms of infection occur while receiving ixekizumab treatment. If a patient develops a serious infection or is not responding to standard therapy while receiving ixekizumab, monitor the patient closely and discontinue ixekizumab therapy until the infection resolves. Patients with a chronic infection or a history of recurrent infections or with underlying conditions that may predispose them to infections (e.g., patients with immunosuppression), or those who have lived in certain infection endemic areas may not be appropriate candidates for ixekizumab therapy. Carefully consider the benefits and risks of therapy before drug initiation.

    Tuberculosis

    Evaluate all patients for tuberculosis before ixekizumab initiation. Ixekizumab should not be administered to patients with active tuberculosis infection. Treatment of latent tuberculosis should be initiated prior to treatment with ixekizumab. Consider antituberculosis therapy before ixekizumab receipt in patients with a history of latent or active tuberculosis without a confirmed adequate treatment course. Monitor patients closely for signs and symptoms of active tuberculosis infection during and after treatment with ixekizumab. Patients who have lived in tuberculosis endemic areas may not be appropriate candidates for ixekizumab therapy. Carefully consider the benefits and risks of therapy before drug initiation.

    Crohn's disease, inflammatory bowel disease, ulcerative colitis

    Use ixekizumab cautiously in patients with inflammatory bowel disease including Crohn's disease and ulcerative colitis. During ixekizumab clinical trials, cases of Crohn's disease and inflammatory bowel disease, including exacerbations, were reported. Monitor patients closely for signs and symptoms of onset or exacerbation of inflammatory bowel disease during ixekizumab treatment.

    Vaccination

    Avoid vaccination of ixekizumab recipients with live virus vaccines. Consider completing all age appropriate immunizations prior to initiating ixekizumab therapy. In addition, no data are available on the response to live or inactive vaccines.

    Pregnancy

    There are no data on the use of ixekizumab during pregnancy and drug-related fetal risks are not known. 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 12 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.

    Breast-feeding

    There are no 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. 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.

    Children, infants

    The safety and efficacy of ixekizumab in children and adolescents less than 18 years of age have not been established. The drug is not indicated for use in infants.

    ADVERSE REACTIONS

    Severe

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

    Moderate

    neutropenia / Delayed / 11.0-11.0
    antibody formation / Delayed / 8.0-10.0
    ocular infection / Delayed / 0-1.3
    conjunctivitis / Delayed / 0-1.3
    candidiasis / Delayed / 0-1.0
    inflammatory bowel disease / Delayed / 0.1-0.2
    thrombocytopenia / Delayed / Incidence not known

    Mild

    infection / Delayed / 27.0-27.0
    injection site reaction / Rapid / 14.0-14.0
    nausea / Early / 2.0-2.0
    influenza / Delayed / 1.3-1.3
    rhinitis / Early / 0-1.0
    urticaria / Rapid / 0-0.1
    pharyngitis / Delayed / Incidence not known

    DRUG INTERACTIONS

    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.
    Baricitinib: (Major) Do not use baricitinib in combination with potent immunosuppressants such as ixekizumab. A risk of added immunosuppression exists when baricitinib is coadministered with potent immunosuppressives. Combined use of multiple-dose baricitinib with potent immunosuppressives has not been studied in patients with rheumatoid arthritis.
    Cyclosporine: (Moderate) 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 ixekizumab administration. Clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as cyclosporine. If ixekizumab is initiated or discontinued in a patient taking cyclosporine, monitor cyclosporine concentrations; cyclosporine dose adjustments may be needed.
    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.
    Rubella 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.
    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) Do not use tofacitinib in combination with biologic immunosuppressives, such as ixekizumab, because of the possibility of increased immunosuppression and increased infection risk. Tofacitinib may be used as monotherapy or concomitantly with methotrexate or other nonbiologic DMARDs. Most patients taking tofacitinib who developed serious infections were taking concomitant immunosuppressives such as methotrexate or corticosteroids.
    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.
    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.
    Warfarin: (Moderate) 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 ixekizumab administration. Clinically relevant drug interactions may occur with CYP450 substrates that have a narrow therapeutic index such as warfarin. If ixekizumab is initiated or discontinued in a patient taking warfarin, monitor the INR; warfarin dose adjustments may be needed.
    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.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no data on the use of ixekizumab during pregnancy and drug-related fetal risks are not known. 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 12 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 are no 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. 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.

    MECHANISM OF ACTION

    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.

    PHARMACOKINETICS

    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.
     
    Affected cytochrome P450 (CYP450) isoenzymes and drug transporters:
    The formation of CYP450 enzymes can be altered by increased levels of certain cytokines and can be increased during chronic inflammation. Theoretically, ixekizumab, an antagonist of interleukin 17A (IL-17A), could normalize the formation of CYP450 enzymes. Drug interaction studies have not been performed.

    Subcutaneous Route

    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.