DRUG INTERACTIONS

Avoid use of live vaccines in patients treated with SKYRIZI. 

U.S. FDA APPROVED  DRUGS DURING 2019

Sr.No-9

ADVERSE REACTIONS

Most common adverse reactions (= 1%) are upper respiratory infections, headache, fatigue, injection site reactions, and tinea infections. (

WARNINGS AND PRECAUTIONS

Infections:

SKYRIZI may increase the risk of infection. Instruct patients to seek medical advice if signs or symptoms of clinically important infection occur. If such an infection develops, do not administer SKYRIZI until the infection resolves. 

• Tuberculosis (TB):

Evaluate for TB prior to initiating treatment with SKYRIZI.

 PATIENT COUNSELING INFORMATION

Advise the patient and/or caregiver to read the FDA-approved patient labeling (Medication Guide and Instructions for Use) before starting SKYRIZI therapy and to reread the Medication Guide each time the prescription is renewed.

Advise patients of the potential benefits and risks of SKYRIZI. Infections Inform patients that SKYRIZI 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 SKYRIZI, 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 SKYRIZI 

Instruct patients or caregivers in the technique of needle and syringe disposal 

Manufactured by:

AbbVie Inc. North Chicago, IL 60064, USA US License Number 1889 © 2019 AbbVie Inc. 20059380 04/2019

 CLINICAL PHARMACOLOGY

1.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.

2. Pharmacodynamics

No formal pharmacodynamics studies have been conducted with risankizumab-rzaa.

3 Pharmacokinetics

Risankizumab-rzaa plasma concentrations increased dose-proportionally from 90 to 180 mg and from 18 to 300 mg (0.6 to 1.2 and 0.12 to 2.0 times the approved recommended following subcutaneous administration in subjects with plaque psoriasis and healthy volunteers, respectively.

Steady-state concentrations were achieved by Week 16 following subcutaneous administration of risankizumab-rzaa at Weeks 0, 4, and every 12 weeks thereafter. At the 150 mg dose, the estimated steady-state peak concentration (Cmax) and trough concentration (Ctrough) were approximately 12 mcg/mL and 2 mcg/mL, respectively.

Absorption

The absolute bioavailability of risankizumab-rzaa was estimated to be 89% following subcutaneous injection. Cmax was reached by 3-14 days.

Distribution

The estimated steady-state volume of distribution (inter-subject CV%) was 11.2 L (34%) in subjects with plaque psoriasis.

Elimination

The estimated systemic clearance (inter-subject CV%) was 0.31 L/day (24%) and terminal elimination half-life was approximately 28 days in subjects with plaque psoriasis.

Metabolism

The metabolic pathway of risankizumab-rzaa has not been characterized. As a humanized IgG1 monoclonal antibody, risankizumab-rzaa is expected to be degraded into small peptides and amino acids via catabolic pathways in a manner similar to endogenous IgG.

Specific Populations

No clinically significant differences in the pharmacokinetics of risankizumab-rzaa were observed based on age (=18 years). No specific studies have been conducted to determine the effect of renal or hepatic impairment on the pharmacokinetics of risankizumab-rzaa.

Body Weight

Risankizumab-rzaa clearance and volume of distribution increase and plasma concentrations decrease as body weight increases; however, no dose adjustment is recommended based on body weight.

Drug Interaction Studies

Cytochrome P450 Substrates No clinically significant changes in exposure of caffeine (CYP1A2 substrate), warfarin (CYP2C9 substrate), omeprazole (CYP2C19 substrate), metoprolol (CYP2D6 substrate), or midazolam (CYP3A substrate) were observed when used concomitantly with risankizumab-rzaa 150 mg administered subcutaneously at Weeks 0, 4, 8 and 12 (more frequent than the approved recommended dosing frequency) in subjects with plaque psoriasis.

 USE IN SPECIFIC POPULATIONS

1. Pregnancy Risk Summary

Limited available data with SKYRIZI use in pregnant women are insufficient to evaluate a drug associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcome.

Human Reference IgG is known to cross the placental barrier; therefore, SKYRIZI may be transmitted from the mother to the developing fetus.

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.

.2. Lactation 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 SKYRIZI and any potential adverse effects on the breastfed infant from SKYRIZI or from the underlying maternal condition.

3. Pediatric Use

The safety and efficacy of SKYRIZI in pediatric patients less than 18 years of age have not yet been established.

4.Geriatric Use

Of the 2234 subjects with plaque psoriasis exposed to SKYRIZI, 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 SKYRIZI. However, the number of subjects aged 65 years and older was not sufficient to determine whether they respond differently from younger subjects.

 OVERDOSAGE

In the event of overdosage, monitor the patient for any signs or symptoms of adverse reactions and administer appropriate symptomatic treatment immediately.