U.S.  APPROVED DRUGS SURING 2022                                        

Serial No 20 

Name-                        SOTYKU

Active Ingredient -   Dcrevacitinib

Pharmacological Classification- To Treat severe plaque psoriasis                                                                                                                                 

                                                                                                                                             Date of Approval-         9/9/2022 

HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use SOTYKTU safely and effectively. See full prescribing information for SOTYKTU. SOTYKTU™ (deucravacitinib) tablets, for oral use

Initial U.S. Approval: 2022

INDICATIONS AND USAGE-

 SOTYKTU is a tyrosine kinase 2 (TYK2) inhibitor indicated for the treatment of adults with moderate-to-severe plaque psoriasis who are candidates for systemic therapy or phototherapy.

 Limitations of Use: Not recommended for use in combination with other potent immunosuppressants.

ADVERSE REACTIONS-

 Most common adverse reactions (= 1%) are upper respiratory infections, blood creatine phosphokinase increased, herpes simplex, mouth ulcers, folliculitis, and acne.

CONTRAINDICATIONS-

 Known hypersensitivity to deucravacitinib or any of the excipients in SOTYKTU. 

WARNINGS AND PRECAUTIONS-

• Hypersensitivity: Hypersensitivity reactions such as angioedema have been reported. Discontinue if a clinically significant hypersensitivity reaction occurs

• Infections: SOTYKTU may increase the risk of infection. Avoid use in patients with active or serious infection. If a serious infection develops, discontinue SOTYKTU until the infection resolves. 

• Tuberculosis: Evaluate for TB prior to initiating treatment with SOTYKTU.

 • Malignancy: Malignancies including lymphomas were observed in clinical trials with SOTYKTU

 • Rhabdomyolysis and elevated CPK.

 • Laboratory Abnormalities: Periodically evaluate serum triglycerides. Evaluate liver enzymes at baseline and thereafter in patients with known or suspected liver disease.

 • Immunizations: Avoid use with live vaccines.

 • Potential Risks Related to JAK Inhibition: It is not known whether TYK2 inhibition may be associated with the observed or potential adverse reactions of JAK inhibition.

Higher rates of all-cause mortality, including sudden cardiovascular death, major adverse cardiovascular events, overall thrombosis, deep venous thrombosis, pulmonary embolism, and malignancies (excluding non-melanoma skin cancer) were observed in patients treated with a JAK inhibitor compared to those treated with TNF blockers in rheumatoid arthritis (RA) patients. SOTYKTU is not approved for use in RA. 

DOSAGE AND ADMINISTRATION-

 • For recommended evaluation prior to SOTYKTU initiation, see Full Prescribing Information.

 • Recommended dosage is 6 mg orally once daily, with or without food. 

DOSAGE FORMS AND STRENGTHS-

 Tablets: 6 mg 

PATIENT COUNSELING INFORMATION-

Advise the patient to read the FDA-approved patient labeling (Medication Guide) before starting SOTYKTU therapy and each time the prescription is renewed, as there may be new information they need to know. Advise patients of the potential benefits and risks of SOTYKTU.

Hypersensitivity Reactions-                                                                                             Advise patients to discontinue SOTYKTU and seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions

Infections-                                                                                                                    Inform patients that SOTYKTU may lower the ability of their immune system to fight infections and to contact their healthcare provider immediately if they develop any signs or symptoms of infection 

Inform patients that herpes infections, including serious, may occur with use of SOTYKTU

 Malignancies including Lymphomas-                                                                            Inform patients that SOTYKTU may increase their risk of developing malignancies including lymphomas. Instruct patients to inform their healthcare provider if they have ever had any type of cancer.

Rhabdomyolysis-                                                                                                           Inform patients that SOTYKTU may increase their risk of developing rhabdomyolysis. Instruct patients to immediately inform their healthcare provider if they develop unexplained muscle pain, tenderness or weakness, particularly if accompanied by malaise or fever

 Laboratory Abnormalities-                                                                                     Inform patients that SOTYKTU may affect certain lab tests, and that blood tests may be required before and during SOTYKTU treatment [see Warnings and Precautions (5.6)]. Immunizations

Advise patients that vaccination with live vaccines is not recommended during SOTYKTU treatment. Medications that interact with the immune system may increase the risk of infection following administration of live vaccines.

Instruct patients to inform the healthcare practitioner that they are taking SOTYKTU prior to a potential vaccination 

Pregnancy Advise patients to report their pregnancy to Bristol-Myers Squibb Company at 1-800-721-5072

Distributed by: Bristol-Myers Squibb Company Princeton, New Jersey 08543 USA

CLINICAL PHARMACOLOGY

1. Mechanism of Action-

Deucravacitinib is an inhibitor of tyrosine kinase 2 (TYK2). TYK2 is a member of the Janus kinase (JAK) family. Deucravacitinib binds to the regulatory domain of TYK2, stabilizing an inhibitory interaction between the regulatory and the catalytic domains of the enzyme.

2. Pharmacodynamics-                                                                                                   In patients with psoriasis, deucravacitinib reduced psoriasis-associated gene expression in psoriatic skin in a dose dependent manner, including reductions in IL-23-pathway and type I IFN pathway regulated genes.

3. Pharmacokinetics- Following oral administration, deucravacitinib plasma Cmax and AUC increased proportionally over a dose range from 3 mg to 36 mg (0.5 to 6 times the approved recommended dosage) in healthy subjects.

Absorption-                                                                                                                         The absolute oral bioavailability of deucravacitinib was 99% and the median Tmax ranged from 2 to 3 hours in healthy subjects.

Food Effect-                                                                                                                    No clinically significant differences in the pharmacokinetics of deucravacitinib were observed following administration of a high-fat, high-calorie meal (951 kcal in total, with approximate distribution of 52% fat, 33% carbohydrate and 15% protein).

Cmax and AUC of deucravacitinib when administered with food were decreased by approximately 24% and 11%, respectively, and Tmax was prolonged by 1 hour.

Cmax and AUC of BMT-153261 when administered with food were decreased by approximately 23% and 10%, respectively, and Tmax was prolonged by 2 hours.

Distribution- The volume of distribution of deucravacitinib at steady state is 140 L. Protein binding of deucravacitinib was 82 to 90% and the blood-to-plasma concentration ratio was 1.26.

Elimination-The terminal half-life of deucravacitinib was 10 hours. The renal clearance of deucravacitinib ranged from 27 to 54 mL/minute.

Metabolism- Deucravacitinib is metabolized by cytochrome P-450 (CYP) 1A2 to form major metabolite BMT153261. Deucravacitinib is also metabolized by CYP2B6, CYP2D6, carboxylesterase (CES) 2, and uridine glucuronyl transferase (UGT) 1A9.

Excretion- After a single dose of radiolabeled deucravacitinib, approximately 13% and 26% of the dose was recovered as unchanged in urine and feces, respectively. Approximately 6% and 12% of the dose was detected as BMT-153261 in urine and feces, respectively.

Specific Populations- Patients with Renal Impairment Deucravacitinib Cmax was 14% lower and 6% higher in patients with mild (eGFR =60 to <90 mL/min/1.73m2 ) and moderate (eGFR =30 to <60 mL/min/1.73m2 ) renal impairment, compared to subjects with normal renal function (eGFR = 90 mL/min/1.73m2 ); no change in Cmax was observed in patients with severe (eGFR <30 mL/min/1.73m2 ) renal impairment, and ESRD (eGFR <15 mL/min/1.73m2 ) on dialysis.

 Dialysis did not substantially clear deucravacitinib from systemic circulation (5.4% of dose cleared per dialysis).

Patients with Hepatic Impairment -Deucravacitinib Cmax was higher by 4%, 10% and 1% in patients with mild (Child-Pugh Class A), moderate (Child-Pugh Class B), and severe (Child-Pugh Class C) hepatic impairment, respectively, compared to subjects with normal hepatic function.

Body Weight, Gender, Race, and Age Body weight, gender, race, and age did not have a clinically meaningful effect on deucravacitinib exposure.

Drug Interaction Studies- Clinical Trials No clinically significant differences in the pharmacokinetics of deucravacitinib were observed when co-administered with the following drugs: Cyclosporine (dual Pgp/BCRP inhibitor), fluvoxamine (CYP1A2 inhibitor), ritonavir (CYP1A2 inducer), diflunisal (UGT 1A9 inhibitor), pyrimethamine (OCT1 inhibitor), famotidine (H2 receptor antagonist), or rabeprazole (proton pump inhibitor).

No clinically significant differences in the pharmacokinetics of the following drugs were observed when co-administered with deucravacitinib: Rosuvastatin, methotrexate, mycophenolate mofetil (MMF) and oral contraceptives (norethindrone acetate and ethinyl estradiol).

USE IN SPECIFIC POPULATIONS

1 Pregnancy Risk Summary

Available data from case reports on SOTYKTU use during pregnancy are insufficient to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. The 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 deucravacitinib in human milk, the effects on the breastfed infant, or the effects on milk production.

Deucravacitinib is present in rat milk. When a drug is present in animal milk, it is likely that the drug will be present in human milk.

 The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for SOTYKTU and any potential adverse effects on the breastfed infant from SOTYKTU or from the underlying maternal condition.

3.Pediatric Use -                                                                                                                 The safety and effectiveness of SOTYKTU in pediatric patients have not been established.

4.Geriatric Use-                                                                                                               Of the 1,519 subjects with plaque psoriasis treated with SOTYKTU.

During the Week 0-16 period, for those subjects (80 subjects = 65 years old, including 12 subjects = 75 years old) who received SOTYKTU without switching treatment arms, there was a higher rate of overall serious adverse reactions, including serious infections, and discontinuations due to adverse reactions compared with younger adults.

No overall differences in effectiveness of SOTYKTU have been observed between patients 65 years of age and older and younger adult patients.

5. Renal Impairment-                                                                                                     No dose adjustment of SOTYKTU is recommended in patients with mild, moderate, or severe renal impairment or in patients with end stage renal disease (ESRD) on dialysis

6.Hepatic Impairment-                                                                                                   No dose adjustment of SOTYKTU is recommended in patients with mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. SOTYKTU is not recommended for use in patients with severe hepatic impairment (Child-Pugh C) .

 OVERDOSAGE-                                                                                                       There is no experience regarding human overdosage with SOTYKTU. In case of overdose, consider contacting the Poison Help line (1-800-222-1222) for additional overdosage management recommendations.

The extent of deucravacitinib elimination by hemodialysis was small (5.4% of dose per dialysis treatment), and thus hemodialysis for treatment of overdose with SOTYKTU is limited.