Deucravacitinib (Monograph)

Brand name: Sotyktu
Drug class: Janus Kinase Inhibitors

Medically reviewed by Drugs.com on May 10, 2024. Written by ASHP.

Introduction

Tyrosine kinase (TYK) 2 inhibitor.

Uses for Deucravacitinib

Plaque Psoriasis

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

Use of deucravacitinib in combination with other potent immunosuppressants not recommended.

Various drugs and drug classes are used to treat psoriasis, including systemic biologic and nonbiologic therapies; deucravacitinib is a nonbiologic option for treatment of this condition.

Recommendations for the 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).

Deucravacitinib Dosage and Administration

General

Pretreatment Screening

Evaluate patients for active and latent tuberculosis infection prior to initiating treatment. If a patient tests positive for tuberculosis, initiate treatment for tuberculosis prior to initiating deucravacitinib.
Consider the risks and benefits prior to initiating deucravacitinib in patients with chronic or recurrent infection or underlying conditions that may predispose them to infection and in those who have been exposed to tuberculosis or who have a history of a serious or opportunistic infection.
Consider viral hepatitis screening prior to initiating deucravacitinib.
Evaluate serum transaminase levels at baseline in patients with known or suspected liver disease.

Patient Monitoring

Closely monitor patients for signs and symptoms of infection during and after treatment with deucravacitinib.
Perform prompt and complete diagnostic testing in patients who develop a new infection during deucravacitinib therapy; initiate appropriate antimicrobial therapy and monitor the patient closely.
Consider monitoring for viral hepatitis reactivation in accordance with clinical guidelines during therapy with deucravacitinib.
Monitor patients for signs and symptoms of active tuberculosis during deucravacitinib therapy.
Periodically evaluate serum triglycerides according to clinical guidelines for hyperlipidemia during therapy.
Evaluate serum transaminase levels during therapy according to routine patient management in patients with known or suspected liver disease.

Other Considerations

Update immunizations, including herpes zoster vaccination, according to current immunization guidelines prior to initiating treatment with deucravacitinib.

Administration

Oral Administration

Administer orally without regard to food.

Swallow tablets intact. Do not crush, cut, or chew.

Dosage

Adults

Plaque Psoriasis

Oral

6 mg once daily.

Special Populations

Hepatic Impairment

Mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment: No dosage adjustment required.

Severe (Child-Pugh class C) hepatic impairment: Use not recommended.

Renal Impairment

No dosage adjustment recommended for patients with mild, moderate, or severe renal impairment, or end-stage renal disease (ESRD) receiving dialysis.

Geriatric Patients

Manufacturer makes no specific dosage recommendations.

Cautions for Deucravacitinib

Contraindications

History of hypersensitivity to deucravacitinib or any ingredient in the formulation.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity reactions, including angioedema, reported. If a clinically important hypersensitivity reaction occurs, discontinue deucravacitinib and initiate appropriate treatment.

Infectious Complications

Possible increased risk of infection. Serious infections, most commonly pneumonia and coronavirus disease 2019 (COVID-19), reported in patients with psoriasis receiving the drug.

Avoid use in patients with an active or serious infection.

Consider risks and benefits prior to initiating deucravacitinib in patients with chronic or recurrent infection or underlying conditions that may predispose them to infection and in those who have been exposed to tuberculosis or who have a history of a serious or opportunistic infection.

Closely monitor patients for signs and symptoms of infection during and after treatment. Perform prompt and complete diagnostic testing in patients who develop a new infection during therapy; initiate appropriate antimicrobial therapy and monitor patient closely.

Interrupt deucravacitinib therapy if a patient develops a serious infection. Do not resume deucravacitinib until infection resolves or is adequately treated.

Herpes virus reactivation (e.g., herpes zoster, herpes simplex) also reported.

Effect of deucravacitinib on chronic viral hepatitis reactivation unknown. Consider viral hepatitis screening and monitoring for reactivation in accordance with clinical guidelines before and during therapy with deucravacitinib. If signs of reactivation occur, consult a hepatitis specialist. Use not recommended in patients with active hepatitis B or hepatitis C.

Active tuberculosis reported. Evaluate patients for latent and active tuberculosis infection prior to initiating deucravacitinib. Avoid use in patients with active tuberculosis. Initiate treatment for latent tuberculosis prior to initiating deucravacitinib. Consider appropriate antimycobacterial therapy prior to initiation of deucravacitinib in patients with a past history of latent or active tuberculosis in whom an adequate course of treatment cannot be confirmed. Monitor patients for signs and symptoms of active tuberculosis during therapy.

Malignancies and Lymphoproliferative Disorders

Malignancies, including lymphomas, reported.

Consider potential benefits and risks prior to initiating or continuing deucravacitinib therapy, particularly in patients with a known malignancy (other than a successfully treated non-melanoma skin cancer) and in those who develop a malignancy while receiving the drug.

Rhabdomyolysis

Cases of rhabdomyolysis resulting in interruption or discontinuance of therapy reported.

Discontinue deucravacitinib in patients who develop markedly elevated creatine phosphokinase (CPK) concentrations or in whom myopathy is diagnosed or suspected. Advise patients to promptly report any unexplained muscle pain, tenderness, or weakness to their clinician, particularly if accompanied by malaise or fever.

Metabolic Effects

Increases in triglyceride levels reported; effects on cardiovascular morbidity and mortality not known.

Periodically evaluate serum triglycerides according to clinical guidelines for hyperlipidemia during therapy. Manage patients according to clinical guidelines.

Hepatic Effects

Serum transaminase elevations ≥3 times the upper limit of normal (ULN) reported.

Evaluate serum transaminase levels at baseline and during therapy according to routine patient management in patients with known or suspected liver disease. If treatment-related increases in liver enzymes occur and drug-induced liver injury is suspected, interrupt deucravacitinib therapy until a diagnosis of liver injury is excluded.

Immunization

Avoid use of live vaccines in patients receiving deucravacitinib. Response to live or non-live vaccines not evaluated in patients receiving the drug.

Consider completion of all age-appropriate immunizations, including prophylactic herpes zoster vaccination, according to current immunization guidelines prior to initiating therapy.

Potential Risks Related to JAK Inhibition

Not known whether TYK2 inhibition may be associated with adverse reactions related to Janus kinase (JAK) inhibition.

Specific Populations

Pregnancy

Available data are insufficient to evaluate a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes.

Report pregnancies to the manufacturer’s adverse event reporting line at 1-800-721-5072.

Lactation

Distributed into milk in rats; not known whether distributed into human milk, affects milk production, or affects the breast-fed infant.

Consider the benefits of breast-feeding and the importance of deucravacitinib to the woman along with 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

An increased incidence of overall serious adverse reactions, including serious infections and discontinuations due to adverse reactions, reported in geriatric patients compared with younger adults.

No overall differences in efficacy observed between geriatric patients and younger adults.

Hepatic Impairment

No dosage adjustment necessary in patients with mild (Child-Pugh class A) or moderate (Child-Pugh class B) hepatic impairment.

Use not recommended in patients with severe (Child-Pugh class C) hepatic impairment.

Renal Impairment

No dosage adjustment necessary in patients with mild, moderate, or severe renal impairment or in patients with ESRD receiving dialysis.

Common Adverse Effects

Adverse effects (reported in ≥1% of patients): Upper respiratory infections, increased CPK concentrations, herpes simplex, mouth ulcers, folliculitis, acne.

Drug Interactions

Metabolized principally by CYP1A2; also metabolized by CYP2B6, CYP2D6, carboxylesterase (CES) 2, and uridine diphosphate-glucuronosyltransferase (UGT) 1A9.

Substrate of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), and organic cation transporter (OCT) 1; not a substrate of organic anion transport protein (OATP), sodium taurocholate cotransporting polypeptide (NTCP), organic anion transporter (OAT) 1, OAT3, OCT2, multidrug and toxin extrusion (MATE) transporter 1, or MATE2-K.

In vitro, does not inhibit CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4. Does not induce CYP1A2, CYP2B6, or CYP3A4. Does not inhibit CES2, UGT1A1, UGT1A4, UGT1A6, UGT1A9, or UGT2B7. Inhibits BCRP and OATP1B3; does not inhibit P-gp, OATP1B1, NTCP, bile salt export pump (BSEP), multidrug resistance protein 2 (MRP2), OAT1, OAT3, OCT1, OCT2, MATE1, or MATE2-K.

Drugs Affecting or Affected by Hepatic Microsomal Enzymes

Clinically important pharmacokinetic interactions unlikely.

Drugs Affecting or Affected by Transport Systems

Clinically important pharmacokinetic interactions unlikely.

Drugs Affecting Gastric Acidity

Clinically important pharmacokinetic interactions unlikely.

Immunosuppressive Agents

Use in combination with other potent immunosuppressants not recommended.

Vaccines

Avoid live vaccines. Response to live or non-live vaccines not evaluated.

Specific Drugs

Drug	Interaction	Comments
Cyclosporine	No clinically important effects on pharmacokinetics of deucravacitinib
Diflunisal	No clinically important effects on pharmacokinetics of deucravacitinib
Famotidine	No clinically important effects on pharmacokinetics of deucravacitinib
Fluvoxamine	No clinically important effects on pharmacokinetics of deucravacitinib
Hormonal contraceptives	No clinically important effects on pharmacokinetics of norethindrone or ethinyl estradiol
Methotrexate	No clinically important effects on pharmacokinetics of methotrexate
Mycophenolate mofetil	No clinically important effects on pharmacokinetics of mycophenolate mofetil
Pyrimethamine	No clinically important effects on pharmacokinetics of deucravacitinib
Rabeprazole	No clinically important effects on pharmacokinetics of deucravacitinib
Ritonavir	No clinically important effects on pharmacokinetics of deucravacitinib
Rosuvastatin	No clinically important effects on pharmacokinetics of rosuvastatin

Deucravacitinib Pharmacokinetics

Absorption

Bioavailability

99%.

Food

No clinically important effects on pharmacokinetics.

Plasma Concentrations

Displays linear pharmacokinetics over oral dosage range of 3–36 mg.

Accumulation <1.4-fold following once-daily dosing in healthy subjects.

Special Populations

Systemic exposure to deucravacitinib is increased by 39% or 28% in patients with moderate or severe renal impairment, and by 34% in patients with ESRD on dialysis, compared to subjects with normal renal function; exposure is not affected in patients with mild renal impairment.

Deucravacitinib exposure is increased by 10%, 40%, and 43% 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, sex, race, and age do not have a clinically meaningful effect on deucravacitinib exposure.

Distribution

Extent

Not known whether deucravacitinib distributes into milk.

Plasma Protein Binding

82–90%.

Elimination

Metabolism

Metabolized by CYP1A2 to form major metabolite BMT-153261; BMT-153261 accounts for approximately 20% of systemic exposure of total drug-related components and has clinical activity similar to parent drug.

Also metabolized by CYP2B6, CYP2D6, CES2, and UGT1A9.

Elimination Route

Following oral administration of radiolabeled deucravacitinib, approximately 13 and 26% of radioactivity recovered as unchanged drug in urine and feces, respectively; BMT-153261 accounted for 6 and 12% of radiolabeled dose in urine and feces, respectively.

Dialysis does not substantially remove deucravacitinib from systemic circulation (5.4% of dose removed per dialysis).

Half-life

10 hours.

Stability

Storage

Oral

Tablets

20–25°C; excursions permitted between 15–30°C.

Actions

Selectively inhibits TYK2, a member of the JAK family of enzymes.
Binds to the regulatory domain of TYK2, stabilizing an inhibitory interaction between the regulatory and the catalytic domains of the enzyme, which results in allosteric inhibition of receptor-mediated activation of TYK2 and its downstream activation of signal transducer and activator of transcription (STAT) proteins.
In patients with psoriasis, reduces psoriasis-associated gene expression in psoriatic skin in a dose-dependent manner, including reductions in IL-23-pathway and type I interferon (IFN) pathway-regulated genes. Reductions in IL-17A, IL-19, and beta-defensin also observed; however, relationship between these pharmacodynamic markers and drug's clinical activity not determined.
Exact mechanism of action in treatment of plaque psoriasis not known.

Advice to Patients

Importance of advising patients to read the FDA-approved patient labeling (medication guide) before initiating therapy and each time prescription is refilled.
Importance of advising patients about potential benefits and risks of deucravacitinib.
Risk of hypersensitivity reactions. Importance of advising patients to discontinue deucravacitinib and seek immediate medical attention if they experience any symptoms of serious hypersensitivity reactions.
Risk of infection. Importance of advising patients that deucravacitinib may lower the ability of their immune system to fight infections and to contact their clinician immediately if they develop any signs or symptoms of infection.
Inform patients that herpes infections, potentially serious, may occur with use of deucravacitinib.
Importance of advising patients that deucravacitinib may increase their risk of developing malignancies, including lymphomas. Importance of informing clinician of a history of any type of cancer.
Risk of rhabdomyolysis. Importance of advising patients to immediately inform their clinician if they develop unexplained muscle pain, tenderness, or weakness, particularly if accompanied by malaise or fever.
Inform patients that deucravacitinib may affect certain lab tests and that blood tests may be required before and during treatment.
Importance of advising patients that vaccination with live vaccines is not recommended during deucravacitinib therapy. Advise patients to inform clinicians that they are receiving the drug prior to any potential vaccination.
Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed. Advise patients to report pregnancies to the manufacturer at 1-800-721-5072.
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.
Importance of informing patients of other important precautionary information. (See Cautions.)

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.