Risankizumab-rzaa (Monograph)

Brand name: Skyrizi
Drug class: Immunomodulatory Agents

Medically reviewed by Drugs.com on Jan 10, 2025. Written by ASHP.

Introduction

Inhibitor of interleukin-23 (IL-23); a recombinant humanized IgG₁ monoclonal antibody that binds specifically to the p19 subunit of IL-23.

Uses for Risankizumab-rzaa

Plaque Psoriasis

Management of moderate to severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.

Guidelines generally support use of IL-23 inhibitors as monotherapy for moderate to severe psoriasis.

Recommendations for use and selection of psoriasis therapies vary based on patient age, disease characteristics (e.g., severity, location, presence of psoriatic arthritis), and comorbidities (e.g., inflammatory bowel disease).

Psoriatic Arthritis

Used for the management of active psoriatic arthritis in adults. May be used alone or in combination with nonbiologic disease-modifying antirheumatic drugs (DMARDs).

The American College of Rheumatology and the National Psoriasis Foundation issued a joint guideline for the treatment of psoriatic arthritis in 2018. Risankizumab is not included in these guidelines; however, current evidence suggests that the drug may provide an additional therapeutic option for patients in whom standard therapies are inadequate.

Recommendations for use and selection of disease-modifying therapies in psoriatic arthritis vary based on the presence of certain disease characteristics (e.g., psoriatic spondylitis/axial disease, enthesitis) and comorbidities (e.g., inflammatory bowel disease, diabetes).

Crohn Disease

Treatment of moderately to severely active Crohn disease in adults.

Risankizumab was approved after publication of recent disease state guidelines; however, some experts hypothesize that risankizumab may provide a unique therapeutic option in select patients because of its greater selectivity for IL-23.

Ulcerative Colitis

Treatment of moderately to severely active ulcerative colitis in adults.

Risankizumab-rzaa Dosage and Administration

General

Pretreatment Screening

Obtain liver enzymes and bilirubin levels prior to initiation of risankizumab therapy for Crohn disease and ulcerative colitis.
Evaluate patients for tuberculosis prior to initiation of risankizumab therapy.
Administer all age-appropriate vaccines recommended by current immunization guidelines prior to initiation of risankizumab therapy.

Patient Monitoring

Monitor patients for signs and symptoms of active tuberculosis during and after risankizumab therapy.
Monitor liver enzymes and bilirubin levels for up to at least 12 weeks during induction therapy for Crohn disease and ulcerative colitis. Monitor thereafter according to routine patient management.

Administration

Administer by sub-Q injection for treatment of plaque psoriasis and psoriatic arthritis. For treatment of Crohn disease and ulcerative colitis, administer induction dosage by IV infusion and maintenance dosage by sub-Q injection.

Sub-Q Administration

Available as single-use prefilled syringes (containing 90 mg/mL or 150 mg/mL), injection pens (containing 150 mg/mL), and prefilled cartridges with an on-body injector (containing 180 mg/1.2 mL or 360 mg/2.4 mL). Should appear as a clear to slightly opalescent, colorless to yellow or slightly yellow (depending on concentration) solution; may contain a few translucent to white particles but should not contain large particulates.

Allow prefilled syringe or injection pen to sit at room temperature inside the carton out of direct sunlight for 15–30 minutes (prefilled syringe) or 30–90 minutes (injection pen) prior to administration. Allow prefilled cartridge with on-body injector to sit at room temperature inside the carton out of direct sunlight for 45–90 minutes prior to administration.

Do not shake the injection.

Administer by sub-Q injection into the upper outer arm, anterior thigh, or abdomen; do not make abdominal injections within 2 inches of the navel. Use thigh or abdomen for self-administration; may use upper arm if administered by a caregiver or clinician. For the on-body injector, initiate injection within 5 minutes after inserting the prefilled cartridge. Do not make injections into areas where the skin is tender, bruised, erythematous, indurated, or affected by psoriasis.

When using multiple syringes to provide a total dose, sequentially inject the full contents of each syringe at different anatomic sites.

Prefilled pens and syringes are intended for use under the supervision of a clinician, but may be self-administered if the clinician determines that the patient and/or their caregiver is competent to prepare and safely administer the drug after appropriate training. Prefilled cartridges with on-body injector are intended for use under the guidance and supervision of a healthcare professional.

If a dose is missed, administer as soon as possible; thereafter, resume dosing at the regularly scheduled time.

IV Infusion

Available as a 600 mg/10 mL injection that must be further diluted prior to IV infusion.

To prepare, determine the dose and number of risankizumab-rzaa vials necessary based on indication for use (Table 1). Subsequently, withdraw 10 mL (600 mg) of solution and inject into an infusion bag or glass bottle containing 5% dextrose or 0.9% sodium chloride (see Table 1) for a final concentration of approximately 1.2–6 mg/mL. Discard any remaining solution in the vial. Allow the diluted solution to warm to room temperature prior to infusion if stored refrigerated. Infuse over a period of at least 1 hour for the 600 mg dose; infuse over at least 2 hours for the 1200 mg dose. Do not administer in the same IV line with other medicinal products. Do not shake the vial or diluted solution in the infusion bag or glass bottle.

Table 1. Total Volume of Diluent Required for IV Risankizumab-rzaa Induction Dose.1
Indication	IV Risankizumab Induction Dose	Number of Risankizumab 600 mg/10 mL Vials	Total Volume of 5% Dextrose or 0.9% Sodium Chloride
Crohn disease	600 mg	1	100 mL, 250 mL, or 500 mL
Ulcerative colitis	1200 mg	2	250 mL or 500 mL

If not used immediately, store diluted solution at 2–8°C and protect from light for up to 20 hours. Immediately after preparation or removal from refrigeration, the diluted solution can be stored at room temperature up to 25°C and protected from sunlight for 4 hours (cumulative time from start of dilution to start of infusion). Exposure to indoor light is acceptable during room temperature storage and administration.

If a dose is missed, administer as soon as possible; thereafter, resume dosing at the regularly scheduled time.

Dosage

Adults

Plaque Psoriasis

Sub-Q

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

If a dose is missed, administer the missed dose as soon as possible and resume dosing at the regularly scheduled interval.

Psoriatic Arthritis

Sub-Q

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

If a dose is missed, administer the missed dose as soon as possible and resume dosing at the regularly scheduled interval.

Crohn Disease

IV Infusion

Induction therapy: 600 mg over at least 1 hour at 0, 4, and 8 weeks.

Sub-Q

Maintenance therapy: 180 mg or 360 mg at week 12, and every 8 weeks thereafter. Use lowest effective dosage to maintain therapeutic response.

Ulcerative Colitis

IV infusion

Induction therapy: 1200 mg over at least 2 hours at weeks 0, 4, and 8.

Sub-Q

Maintenance therapy: 180 mg or 360 mg at week 12, and every 8 weeks thereafter. Use lowest effective dosage to maintain therapeutic response.

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.

Renal Impairment

No specific dosage recommendations at this time.

Geriatric Use

No specific dosage recommendations at this time.

Cautions for Risankizumab-rzaa

Contraindications

History of serious hypersensitivity reactions to risankizumab or any excipients in the formulation.

Warnings/Precautions

Hypersensitivity Reactions

Serious hypersensitivity reactions, including anaphylaxis, reported.

If a serious hypersensitivity reaction occurs, immediately discontinue the drug and initiate appropriate therapy.

Infections

May increase risk of infection. In clinical trials in patients with psoriasis, upper respiratory tract infections and tinea infections occurred more frequently with risankizumab-rzaa than with placebo.

Do not initiate risankizumab in patients with any clinically important active infection until infection resolves or is adequately treated. Consider risks and benefits before initiating therapy in patients with chronic infection or history of recurrent infection.

If clinically important infection develops or does not respond to standard therapy, monitor patient closely and discontinue risankizumab until infection resolves.

Tuberculosis

Evaluate patients for tuberculosis prior to initiation of risankizumab. Do not administer to patients with active tuberculosis. Consider antimycobacterial therapy prior to initiating risankizumab therapy in individuals with a history of latent or active tuberculosis in whom an adequate course of antimycobacterial treatment cannot be confirmed. Closely monitor patients for active tuberculosis during and after risankizumab treatment.

Hepatotoxicity in Treatment of Inflammatory Bowel Disease

Evaluate liver enzymes and bilirubin at baseline and for up to at least 12 weeks during induction and maintenance treatment of Crohn disease and ulcerative colitis. Monitor thereafter according to routine management. Consider alternate treatment in patients with evidence of liver cirrhosis. Interrupt treatment if drug-induced liver injury is suspected, until cause of liver enzyme elevation is confirmed. Instruct patients to seek medical attention if they experience symptoms of hepatic dysfunction.

Administration of Vaccines

Administer all age-appropriate vaccines recommended by current immunization guidelines prior to initiating risankizumab.

Avoid live vaccines during therapy.

Immunogenicity

Antibodies to risankizumab-rzaa, including neutralizing antibodies, reported. High anti-drug antibody titers (detected in approximately 1% of patients receiving risankizumab-rzaa) associated with decreased drug concentrations and decreased efficacy. In clinical studies in psoriatic arthritis, anti-drug antibodies also associated with higher frequency of hypersensitivity and injection-site reactions.

Specific Populations

Pregnancy

Data regarding use in pregnant women are inadequate to establish risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Potential for fetal exposure since human IgG crosses the placenta. Consider delaying administration of live vaccines for a minimum of 5 months to infants exposed to risankizumab in utero.

Dose-dependent increase in fetal/infant loss observed in pre- and post-natal developmental study in cynomolgus monkeys; no malformations and no adverse effects on growth and development, immunologic development, or neurobehavioral development observed. Clinical relevance unknown.

Pregnancy registry at 877-302-2161 or [Web].

Lactation

Not known whether risankizumab distributes into human milk, affects milk production, or affects breast-fed infants. Maternal IgG is present in breast milk.

Because risankizumab is a large protein molecule, absorption by a breast-fed infant is unlikely since the drug will probably be destroyed in the infant's GI tract. Effects of local GI and limited systemic exposure in the breast-fed infant unknown.

Consider benefits of breast-feeding and importance of the drug to the woman; also consider any potential adverse effects on the breast-fed infant from the drug or underlying maternal condition.

Pediatric Use

Safety and efficacy not established in pediatric patients.

Geriatric Use

Clinical trials of patients for each approved indication did not include sufficient numbers of patients ≥65 years of age to determine whether they respond differently than younger adults. No clinically meaningful differences in pharmacokinetics in geriatric versus younger patients with Crohn disease.

Hepatic Impairment

Pharmacokinetic data in patients with hepatic impairment not available.

Renal Impairment

Pharmacokinetic data in patients with renal impairment not available.

Common Adverse Effects

Adverse reactions (≥1%) in patients with plaque psoriasis and psoriatic arthritis: upper respiratory infection, headache, fatigue, injection site reaction, tinea infection.

Adverse reactions (>3%) in patients receiving induction treatment for Crohn disease: upper respiratory infection, headache, arthralgia.

Adverse reactions (>3%) in patients receiving maintenance treatment for Crohn disease: arthralgia, injection site reaction, abdominal pain, anemia, pyrexia, back pain, arthropathy, urinary tract infection.

Adverse reactions (≥3%) in patients receiving induction treatment for ulcerative colitis: arthralgia.

Adverse reactions (≥3%) in patients receiving maintenance treatment for ulcerative colitis: arthralgia, pyrexia, injection site reactions, rash.

Drug Interactions

Vaccines

Avoid live vaccines. No data available regarding response to live or inactivated vaccines in patients receiving risankizumab.

Specific Drugs

Drug	Interaction
Caffeine	No clinically important effect on AUC of caffeine (CYP1A2 substrate)
Metoprolol	No clinically important effect on AUC of metoprolol (CYP2D6 substrate)
Midazolam	No clinically important effect on AUC of midazolam (CYP3A4 substrate)
Omeprazole	No clinically important effect on AUC of omeprazole (CYP2C19 substrate)
Warfarin	No clinically important effect on AUC of warfarin (CYP2C9 substrate)

Risankizumab-rzaa Pharmacokinetics

Absorption

Bioavailability

Absolute bioavailability is approximately 74-89% following sub-Q administration.

Peak concentration achieved within 3–14 days following a single sub-Q dose; steady-state concentrations attained by week 16 when administered at weeks 0 and 4 and every 12 weeks thereafter.

Concentrations are dose proportional over sub-Q dose range of 18–360 mg and over the IV infusion dose range of 200-1800 mg in healthy individuals.

Special Populations

Plasma concentrations are lower in patients with higher body weight.

Distribution

Extent

Not known whether distributed into human milk.

Elimination

Metabolism

Metabolic pathway not characterized. Expected to be degraded into small peptides and amino acids via catabolic pathways in similar manner as endogenous IgG.

Half-life

28 days in patients with plaque psoriasis.

21 days in patients with Crohn disease.

Special Populations

Age does not substantially alter clearance. Drug exposure comparable in patients ≥65 years of age and younger adults with Crohn disease.

Pharmacokinetics not formally studied in renal or hepatic impairment.

Pharmacokinetics generally similar in patients with ulcerative colitis or Crohn disease.

Stability

Storage

Parenteral

Injection, for Sub-Q Use

2–8°C; do not freeze. Store in original carton to protect from light until use.

Injection, for IV Infusion

2–8°C; do not freeze. Store in original carton to protect from light until use.

Actions

Binds with specificity to the p19 subunit of IL-23, a naturally occurring cytokine that stimulates production of proinflammatory cytokines, including interleukin-17 (IL-17) and interleukin-22 (IL-22). IL-17 and IL-22 contribute to chronic inflammation in patients with psoriasis.
Disrupts IL-23-mediated signaling and inhibits release of proinflammatory cytokines and chemokines.

Advice to Patients

Instruct patient and/or caregiver regarding proper storage, dosage, and administration of risankizumab, including the use of aseptic technique, and proper disposal of needles and syringes or injection pens if it is determined that the patient and/or caregiver is competent to safely administer the drug.
Counsel patients on possible increased susceptibility to infections. Advise patients to promptly inform clinician if any signs or symptoms of infection (e.g., fever, sweats, or chills; muscle aches; cough, shortness of breath, or blood in the phlegm; weight loss; warm, red, or painful sores on the body; diarrhea or stomach pain; burning upon urination or increased urination) occur.
Advise patients to inform their clinician if they have an active tuberculosis infection or have latent tuberculosis because treatment may be required before initiating risankizumab therapy.
Advise patients with Crohn disease and ulcerative colitis regarding the need for liver enzyme and bilirubin monitoring. Instruct patients to seek immediate medical attention if they experience unexplained rash, nausea, vomiting, stomach pain, tiredness, loss of appetite, yellowing of the skin and eyes, and/or dark urine.
Advise patients to review vaccination status with their clinician and receive all appropriate vaccinations prior to initiation of risankizumab. Advise patients that they should not receive live vaccines during or immediately before or after risankizumab therapy. Instruct patients to inform clinicians that they are receiving risankizumab prior to receiving any vaccine.
Advise patients to inform clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs, as well as any concomitant illnesses (e.g., active infection) or any history of tuberculosis or other infections.
Advise women to inform clinicians if they are or plan to become pregnant or plan to breast-feed. Encourage pregnant women to enroll in a pregnancy registry if exposed to risankizumab.
Advise women who took risankizumab during pregnancy to wait at least 5 months to have live vaccines administered to their infant.
Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Risankizumab is available from specialty pharmacies. For information on access and options for insured and uninsured patients, visit [Web].

Risankizumab-rzaa
Routes	Dosage Forms	Strengths	Brand Names	Manufacturer
Parenteral	Injection, for subcutaneous use	90 mg/mL	Skyrizi (available as single-dose prefilled syringes)
		150 mg/mL	Skyrizi (available as single-dose prefilled syringes and injection pens)	AbbVie
		180 mg/1.2 mL	Skyrizi (available as prefilled cartridges with on-body injector)
		360 mg/2.4 mL	Skyrizi (available as prefilled cartridges with on-body injector)
	Injection, for IV use	600 mg/10 mL (60 mg/mL)	Skyrizi (available as single-dose vials)