Class: Skin and Mucous Membrane Agents, Miscellaneous
Chemical Name: Immunoglobulin G1, anti-(human interleukin 23 subunit p19) (human-Mus musculus heavy chain), disulfide with human-Mus musculus κ-chain, dimer
Molecular Formula: C6476H9992N1720O2016S44C3H8O
CAS Number: 1612838-76-2
Risankizumab-rzaa, a recombinant DNA-derived humanized immunoglobulin G1 (IgG1) monoclonal antibody, is an antipsoriatic agent.
Uses for Risankizumab-rzaa
Risankizumab-rzaa has the following uses:
Risankizumab-rzaa is an interleukin-23 antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy.
Risankizumab-rzaa Dosage and Administration
Risankizumab-rzaa is available in the following dosage form(s) and strength(s):
Injection: 75 mg/0.83 mL in each single-dose prefilled syringe.
It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:
Dosage and Administration
150 mg (two separate 75 mg injections) administered by subcutaneous injection at Week 0, Week 4 and every 12 weeks thereafter.
For each dose, administer the injections at different anatomic locations (e.g., thighs, abdomen) avoiding skin that is tender, bruised, erythematous, indurated, or affected by psoriasis.
Intended for use under the guidance and supervision of a healthcare professional.
Cautions for Risankizumab-rzaa
Risankizumab-rzaa may increase the risk of infections. In clinical studies, infections occurred in 22.1% of the risankizumab-rzaa group compared to 14.7% of the placebo group through 16 weeks of treatment. Upper respiratory tract infections and tinea infections occurred more frequently in the risankizumab-rzaa group than in the placebo group. Subjects with known chronic or acute infections were not enrolled in clinical studies.
The rate of serious infections for the risankizumab-rzaa group and the placebo group was ≤ 0.4%. Treatment with risankizumab-rzaa should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated.
In patients with a chronic infection or a history of recurrent infection, consider the risks and benefits prior to prescribing risankizumab-rzaa. Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur. If a patient develops such an infection or is not responding to standard therapy, monitor the patient closely and do not administer risankizumab-rzaa until the infection resolves.
Pre-treatment Evaluation for Tuberculosis
Evaluate patients for tuberculosis (TB) infection prior to initiating treatment with risankizumab-rzaa. Across the Phase 3 psoriasis clinical studies, of the 72 subjects with latent TB who were concurrently treated with risankizumab-rzaa and appropriate TB prophylaxis during the studies, none developed active TB during the mean follow-up of 61 weeks on risankizumab-rzaa. Two subjects taking isoniazid for treatment of latent TB discontinued treatment due to liver injury. Of the 31 subjects from the IMMHANCE study with latent TB who did not receive prophylaxis during the study, none developed active TB during the mean follow-up of 55 weeks on risankizumab-rzaa. Consider anti-TB therapy prior to initiating risankizumab-rzaa in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Monitor patients for signs and symptoms of active TB during and after risankizumab-rzaa treatment. Do not administer risankizumab-rzaa to patients with active TB.
Prior to initiating therapy with risankizumab-rzaa, consider completion of all age appropriate immunizations according to current immunization guidelines. Avoid use of live vaccines in patients treated with risankizumab-rzaa. No data are available on the response to live or inactive vaccines.
Risk Summary: Limited available data with risankizumab-rzaa use in pregnant women are insufficient to evaluate a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcome. Human IgG is known to cross the placental barrier; therefore, risankizumab-rzaa may be transmitted from the mother to the developing fetus.
In an enhanced pre- and post-natal developmental toxicity study, pregnant cynomolgus monkeys were administered subcutaneous doses of 5 and 50 mg/kg risankizumab-rzaa once weekly during the period of organogenesis up to parturition. At the 50 mg/kg dose [20 times the maximum recommended human dose (MRHD); 2.5 mg/kg based on administration of a 150 mg dose to a 60 kg individual], increased fetal/infant loss was noted in pregnant monkeys. No risankizumab-rzaa-related effects on functional or immunological development were observed in infant monkeys from birth through 6 months of age. The clinical significance of these findings for humans is unknown.
All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Animal Data: An enhanced pre- and post-natal developmental toxicity study was conducted in cynomolgus monkeys. Pregnant cynomolgus monkeys were administered weekly subcutaneous doses of risankizumab-rzaa of 5 or 50 mg/kg from gestation day 20 to parturition and the cynomolgus monkeys (mother and infants) were monitored for 6 months after delivery. No maternal toxicity was noted in this study. There were no treatment-related effects on growth and development, malformations, developmental immunotoxicology or neurobehavioral development. However, a dose-dependent increase in fetal/infant loss was noted in the risankizumab-rzaa-treated groups (32% and 43% in the 5 mg/kg and 50 mg/kg groups, respectively) compared to the vehicle control group (19%). The increased fetal/infant loss in the 50 mg/kg group was considered to be related to risankizumab-rzaa treatment. The no observed adverse effect level (NOAEL) for maternal toxicity was identified as 50 mg/kg (20 times the MRHD, based on mg/kg comparison) and the NOAEL for developmental toxicity was identified as 5 mg/kg (2 times the MRHD, based on mg/kg comparison). In the infants, mean serum concentrations increased in a dose-dependent manner and were approximately 17-86% of the respective maternal concentrations. Following delivery, most adult female cynomolgus monkeys and all infants from the risankizumab-rzaa-treated groups had measurable serum concentrations of risankizumab-rzaa up to 91 days postpartum. Serum concentrations were below detectable levels at 180 days postpartum.
Risk Summary: There are no data on the presence of risankizumab-rzaa in human milk, the effects on the breastfed infant, or the effects on milk production. Maternal IgG is known to be present in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for risankizumab-rzaa and any potential adverse effects on the breastfed infant from risankizumab-rzaa or from the underlying maternal condition.
The safety and efficacy of risankizumab-rzaa in pediatric patients less than 18 years of age have not yet been established.
Of the 2234 subjects with plaque psoriasis exposed to risankizumab-rzaa, 243 subjects were 65 years or older and 24 subjects were 75 years or older. No overall differences in risankizumab-rzaa exposure, safety or effectiveness were observed between older and younger subjects who received risankizumab-rzaa. However, the number of subjects aged 65 years and older was not sufficient to determine whether they respond differently from younger subjects.
Common Adverse Effects
Most common adverse reactions (≥ 1%) are upper respiratory infections, headache, fatigue, injection site reactions, and tinea infections.
It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:
Avoid use of live vaccines in patients treated with risankizumab-rzaa.
Mechanism of Action
Risankizumab-rzaa is a humanized immunoglobulin G1 (IgG1) monoclonal antibody that selectively binds to the p19 subunit of human interleukin 23 (IL-23) cytokine and inhibits its interaction with the IL-23 receptor. IL-23 is a naturally occurring cytokine that is involved in inflammatory and immune responses.
Risankizumab-rzaa inhibits the release of pro-inflammatory cytokines and chemokines.
Advice to Patients
Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use) before starting risankizumab-rzaa therapy and to reread the Medication Guide each time the prescription is renewed. Advise patients of the potential benefits and risks of risankizumab-rzaa.
Inform patients that risankizumab-rzaa may lower the ability of their immune system to fight infections. Instruct patients of the importance of communicating any history of infections to the healthcare provider and contacting their healthcare provider if they develop any symptoms of an infection.
Instruct patients or caregivers to perform the first self-injected dose under the supervision and guidance of a qualified healthcare professional for training in preparation and administration of risankizumab-rzaa, including choosing anatomical sites for administration, and proper subcutaneous injection technique.
Instruct patients or caregivers to administer two 75 mg single-dose syringes to achieve the 150 mg dose of risankizumab-rzaa.
Instruct patients or caregivers in the technique of needle and syringe disposal.
AHFSfirstRelease™. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.
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.
Injection, for subcutaneous use
75 mg/0.83 mL
Skyrizi (available as single-use prefilled syringes with alcohol swabs)
AHFS Drug Information. © Copyright 2021, Selected Revisions May 13, 2019. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
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