Skyrizi

Antipsoriatic Monoclonal Antibodies and Others

Keep the product in the original carton to protect from light until time of use.
Do not shake the carton, vials, prefilled pen, or prefilled syringe(s).
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. The solution may contain a few translucent white particles.
Do not use if solution contains large particles or is cloudy or discolored; solution has been frozen; prefilled pen or syringe has been dropped or damaged; carton perforations are broken.[64073]

For Crohn's disease (Intravenous induction regimen):
Only administer intravenously by infusion, infusion must be administered by a qualified health care professional using aseptic technique.
Dilute prior to IV infusion administration. Withdraw 10 mL of risankizumab solution from the vial and inject into an intravenous infusion bag or glass bottle containing 5% Dextrose Injection (600 mg/10 mL in 100 mL, or 250 mL, or 500 mL) for a final concentration of approximately 1.2 mg/mL to 6 mg/mL.
Discard any remaining solution in the vial.
Do not shake the vial or diluted solution in the infusion bag or glass bottle.
Allow the diluted risankizumab solution in the infusion bag or glass bottle to warm to room temperature (if stored refrigerated) prior to the start of the intravenous infusion.
Infuse IV over a period of at least 1 hour. Complete the IV infusion within 8 hours of dilution.
Do not administer risankizumab IV infusion in the same intravenous line with other medicinal products.
Storage of Prepared Infusion: If not used immediately, store the diluted infusion solution refrigerated and protected from light for up to 20 hours between 2 and 8 degrees C (36 and 46 degrees F). Subsequently, the diluted solution can be stored (protected from direct and indirect sunlight) for 8 hours at room temperature at up to 25 degrees C (77 degrees F) after dilution (cumulative time after preparation including the storage and the infusion period). Do not freeze.

For plaque psoriasis and psoriatic arthritis:
Only an individual trained in subcutaneous drug delivery should administer the injection. An adult who is properly trained in injection technique may self-inject using the prefilled pen or syringe(s), if the prescriber deems the action appropriate. However, the first injection needs to be under the supervision of a qualified health care professional.
Refer to the "Instructions for Use" to find more detailed instructions on preparation and administration.
Prior to administration, remove from the refrigerator and allow the prefilled pen or syringe(s) (in the carton) to reach room temperature out of direct sunlight. Approximate time to reach room temperature is 30 to 90 minutes for the prefilled pen and 15 to 30 minutes for the prefilled syringe(s). Do not use other methods to speed the warming process.
Wash and dry hands.
Select an injection site and wipe with an alcohol swab in a circular motion. Injection sites include right or left thigh, abdomen at least 2 inches from the navel. Do not inject into skin that is tender, bruised, red, hard, or affected by psoriasis. Do not inject into a scar or stretch mark.
For the 75 mg and 150 mg prefilled syringe(s):
Gather either one 150 mg or two 75 mg prefilled syringes.
Remove the needle cover from the prefilled syringe. If using the 75 mg prefilled syringes, only remove the needle cover from 1 of the syringes.
With 1 hand, gently pinch the cleaned injection site. Use the other hand to insert the needle at a 45-degree angle using a quick short movement.
Slowly push the plunger rod in until all the solution is injected and the syringe is empty.
Pull the needle out of the skin at the same angle. Release the plunger rod and allow the prefilled syringe to move up until the entire needle is covered by the needle guard. The needle guard will not activate unless all the liquid has been injected.
Apply a cotton ball or gauze pad over the injection site for 10 seconds. Do not rub the injection site.
To obtain the full dose when using the 75 mg prefilled syringes, repeat the process using the second 75 mg prefilled syringe immediately after the first injection. Select and cleanse an alternative injection site that is at least 1 inch away from the first site; do not inject into the same site as the first syringe.
For the 150 mg prefilled pen:
Gather one 150 mg prefilled pen.
Hold the pen with the fingers on the gray hand grips, so that the dark gray cap is pointing up. Pull the dark gray cap straight off.
Turn the pen, while the fingers are on the gray hand grips, so that the white needle sleeve points toward the injection site, and you can see the green activator button.
With the other hand, pinch the skin at the injection site to make a raised area.
Place the white needle sleeve straight (90-degree angle) against the raised injection site. Push and keep pressing the pen down against the injection site. The pen will only activate if the white needle sleeve is pressed down against the injection site before the green activator button is pressed.
Press the green activator button and hold the pen down against the injection site for 15 seconds. The first loud click means the injection has started. A second click will sound once the injection is complete and the yellow indicator has filled the inspection window. The injection process takes up to 15 seconds.
Slowly pull the pen straight out from the skin. The white needle sleeve will cover the needle tip and make another click.
Apply a cotton ball or gauze pad over the injection site for 10 seconds. Do not rub the injection site.
Prefilled pens and syringes are single-use only; the drug solution does not contain preservatives. Immediately discard pen or syringe and any unused product in a proper sharps disposal container. [64073]
 
For Crohn's disease (maintenance dosing after induction regimen is complete)
Subcutaneous Maintenance Dosing Regimen:
Subcutaneous administration is intended for use under the guidance and supervision of a health care professional.
Patients may self-inject subcutaneous risankizumab using the on-body injector with prefilled cartridge after training in subcutaneous injection technique. Provide proper training to patients and/or caregivers on the subcutaneous injection technique.
Refer to the "Instructions for Use" to find more detailed instructions on preparation and administration.
Before using the on-body injector with prefilled cartridge, remove the carton from the refrigerator and allow to reach room temperature out of direct sunlight (45 to 90 minutes) without removing the prefilled cartridge or on-body injector from the carton.
Use the on-body injector to administer the prefilled cartridge subcutaneously on thigh or abdomen.
Do not inject into areas where the skin is tender, bruised, erythematous, indurated or affected by any lesions.
Missed dose: If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time.

anaphylactoid reactions / Rapid / Incidence not known
hepatotoxicity / Delayed / Incidence not known

antibody formation / Delayed / 3.4-24.0
elevated hepatic enzymes / Delayed / 1.1-5.4
anemia / Delayed / 0-4.9
osteomyelitis / Delayed / 0-0.4
atopic dermatitis / Delayed / Incidence not known
hematoma / Early / Incidence not known
hyperlipidemia / Delayed / Incidence not known
hypercholesterolemia / Delayed / Incidence not known

infection / Delayed / 22.1-36.6
influenza / Delayed / 10.6-10.6
pharyngitis / Delayed / 10.6-10.6
nasal congestion / Early / 10.6-10.6
arthralgia / Delayed / 0-9.2
abdominal pain / Early / 0-8.5
headache / Early / 3.5-6.6
injection site reaction / Rapid / 0.7-5.6
fever / Early / 2.6-4.9
back pain / Delayed / 0-4.2
arthropathy / Delayed / 0-3.5
fatigue / Early / 0-2.5
asthenia / Delayed / 0-2.5
folliculitis / Delayed / 0.1-1.0
urticaria / Rapid / 0.1-1.0
rash / Early / 0.7-0.7
sinusitis / Delayed / Incidence not known
rhinitis / Early / Incidence not known
pruritus / Rapid / Incidence not known
ecchymosis / Delayed / Incidence not known

Skyrizi

Rx

Subcutaneous IgG1 monoclonal antibody that inhibits interleukin-23 (IL-23)
Used for moderate to severe plaque psoriasis and active psoriatic arthritis in adults; also used for adults with moderate to severely active Crohn's disease (CD)
May increase risk of infection and may cause hypersensitivity reactions; evaluate all patients for active or latent tuberculosis infection before starting therapy

150 mg subcutaneously at weeks 0 and 4, then 150 mg subcutaneously every 12 weeks.

150 mg subcutaneously at weeks 0 and 4, then 150 mg subcutaneously every 12 weeks. Risankizumab can be administered as monotherapy or in combination with non-biologic disease-modifying antirheumatic drugs (DMARDs).

600 mg IV infusion over at least 1 hour at week 0, week 4, and week 8. Obtain hepatic enzymes and bilirubin levels prior to initiating treatment. Follow with maintenance treatment subcutaneously.

180 mg or 360 mg subcutaneously at week 12, and every 8 weeks after that. Use the lowest effective dosage to maintain therapeutic response.

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

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

Bacillus Calmette-Guerin Vaccine, BCG: (Major) Avoid administration of live vaccines to risankizumab recipients. Before initiation of risankizumab 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 risankizumab therapy.
Intranasal Influenza Vaccine: (Major) Avoid administration of live vaccines to risankizumab recipients. Before initiation of risankizumab 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 risankizumab therapy.
Live Vaccines: (Major) Avoid administration of live vaccines to risankizumab recipients. Before initiation of risankizumab 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 risankizumab therapy.
Measles Virus; Mumps Virus; Rubella Virus; Varicella Virus Vaccine, Live: (Major) Avoid administration of live vaccines to risankizumab recipients. Before initiation of risankizumab 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 risankizumab therapy.
Measles/Mumps/Rubella Vaccines, MMR: (Major) Avoid administration of live vaccines to risankizumab recipients. Before initiation of risankizumab 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 risankizumab therapy.
Rotavirus Vaccine: (Major) Avoid administration of live vaccines to risankizumab recipients. Before initiation of risankizumab 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 risankizumab therapy.
Smallpox and Monkeypox Vaccine, Live, Nonreplicating: (Major) Avoid administration of live vaccines to risankizumab recipients. Before initiation of risankizumab 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 risankizumab therapy.
Smallpox Vaccine, Vaccinia Vaccine: (Major) Avoid administration of live vaccines to risankizumab recipients. Before initiation of risankizumab 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 risankizumab therapy.
Typhoid Vaccine: (Major) Avoid administration of live vaccines to risankizumab recipients. Before initiation of risankizumab 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 risankizumab therapy.
Varicella-Zoster Virus Vaccine, Live: (Major) Avoid administration of live vaccines to risankizumab recipients. Before initiation of risankizumab 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 risankizumab therapy.
Yellow Fever Vaccine, Live: (Major) Avoid administration of live vaccines to risankizumab recipients. Before initiation of risankizumab 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 risankizumab therapy.

Risankizumab/Skyrizi Subcutaneous Inj Sol: 0.83mL, 1mL, 1.2mL, 2.4mL, 75mg, 150mg, 180mg, 360mg
Skyrizi Intravenous Inj Sol: 10mL, 600mg

Psoriasis and Psoriatic Arthritis: 150 mg/dose subcutaneously at Week 0, Week 4, and every 12 weeks after that.
Crohn's disease: 600 mg single IV induction dose for Crohn's disease at week 0, 4, and 8; then 360 mg/dose subcutaneously at week 12 and for maintenance every 8 weeks after that.

Psoriasis and Psoriatic Arthritis: 150 mg/dose subcutaneously at Week 0, Week 4, and every 12 weeks after that.
Crohn's disease: 600 mg single IV induction dose for Crohn's disease at week 0, 4, and 8; then 360 mg/dose subcutaneously at week 12 and for maintenance every 8 weeks after that.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Risankizumab is a humanized immunoglobulin G1 (IgG1) 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 its receptor, risankizumab prevents the release of proinflammatory cytokines and chemokines.[64073]

Risankizumab is administered via subcutaneous injection. Once in systemic circulation, the steady-state volume of distribution is 11.2 L in subjects with plaque psoriasis, and 7.68 L in subjects with Crohn's disease. Although a metabolic pathway has not been characterized, risankizumab is expected to be degraded to small peptides and amino acids via catabolic pathways in the same manner as endogenous human immunoglobulin G (IgG). The drug exhibits a systemic clearance of 0.31 L/day and 0.30 L/day and terminal elimination half-life was approximately 28 days and 21 days in subjects with plaque psoriasis and Crohn's disease, respectively.[64073]
 
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: None

Increases in risankizumab plasma concentrations were proportional following administration of single doses from 200 mg to 1800 mg (0.3 to 3 times the recommended dose) intravenously infused (up to 3 hour infusion time). In subjects with Crohn's disease treated with 600 mg intravenous induction dose at Weeks 0, 4, and 8, followed by 360 mg subcutaneous maintenance dose at Week 12 and every 8 weeks thereafter, the median Cmax and Cmin are estimated to be 156 mcg/mL and 38.8 mcg/mL, respectively, during Weeks 8 to 12; and the steady state median Cmax and Cmin are estimated to be 28 mcg/mL and 8.13 mcg/mL, respectively, during Weeks 40 to 48.

The absolute bioavailability of risankizumab is estimated to be 74% to 89%, with peak serum concentrations (Cmax) being reached 3 to 14 days post-dose. The drug exhibits linear pharmacokinetics with exposures increasing proportionally over a dose range from 18 mg (0.05-times the lowest recommended dose) to 300 mg (2.4-times the highest recommended dose). In individuals with psoriatic indications, risankizumab 150 mg administered on weeks 0 and 4 followed by every 12 weeks produces steady-state peak and trough concentrations of 12 mcg/mL and 2 mcg/mL, respectively. In subjects with Crohn's disease treated with 600 mg IV induction dose at Weeks 0, 4, and 8, followed by 180 mg or 360 mg subcutaneous maintenance dose at Week 12 and every 8 weeks thereafter, the median Cmax and Cmin are estimated to be 156 mcg/mL and 38.8 mcg/mL, respectively, during Weeks 8 to 12. The steady state median Cmax and Cmin are estimated to be 14 mcg/mL and 4.1 mcg/mL, respectively, for 180 mg and 28 mcg/mL and 8.1 mcg/mL, respectively, for 360 mg during Weeks 40 to 48.[64073]

Data regarding the use of risankizumab during pregnancy are insufficient to determine the drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Human immunoglobulin G (IgG) does cross the placental barrier; therefore, risankizumab may be transferred from mother to fetus. In animal studies involving pregnant cynomolgus monkeys, no adverse effects on neonatal growth or development were observed following maternal doses of 5 and 50 mg/kg (2- and 20-times maximum recommended human dose) administered from gestation day 20 to parturition. However, a dose-dependent increase in fetal loss was noted in the risankizumab-treated groups (32% and 43% for the 5 mg/kg and 50 mg/kg groups, respectively) compared with the vehicle control group (19%). The clinical significance of these findings for humans is unknown. There is a pregnancy exposure registry that monitors outcomes in women who become pregnant while receiving risankizumab; patients are encouraged to enroll by calling 1-877-302-2161.[64073]

There are no data on the presence of risankizumab in human milk, the effects on breastfed infants, or the effects on milk production; however, maternal immunoglobulin G (IgG) is known to be present in human milk. Consider the benefits of breast-feeding along with the mother's clinical need for risankizumab.[64073]