Cravacin

A. Approved Indications

• Moderate to Severe Plaque Psoriasis (PsO) in Adults
• Indicated for adults who are candidates for systemic therapy or phototherapy.

B. Clinically Accepted Off-Label Uses

• Psoriatic Arthritis (PsA)
• Under investigation; used in some cases off-label based on TYK2 pathway role in inflammation.
• Systemic Lupus Erythematosus (SLE)
• Investigational use in patients with active SLE; not yet approved but studied in phase 2/3 trials.

A. Adults

• Recommended Dose: 6 mg once daily with or without food.

B. Pediatric Use

• Not approved for use in individuals under 18 years.
• Safety and efficacy in this population have not been established.

C. Elderly

• No dose adjustment needed.
• Monitor for increased risk of infection or liver function abnormalities.

D. Renal Impairment

• Mild to moderate impairment: No dose adjustment required.
• Severe impairment or ESRD: Use with caution; data are limited.

E. Hepatic Impairment

• Mild to moderate impairment (Child-Pugh A or B): No dose adjustment required.
• Severe hepatic impairment (Child-Pugh C): Not recommended due to lack of data.

Route of Administration: Oral

Duration of Use: Long-term use; periodic assessment of effectiveness and safety recommended.

Deucravacitinib is a selective allosteric inhibitor of Tyrosine Kinase 2 (TYK2), a member of the Janus kinase (JAK) family. TYK2 is critical in mediating the signaling of key cytokines involved in inflammatory pathways, including interleukin-23 (IL-23), IL-12, and type I interferons. By selectively binding to the regulatory domain of TYK2, rather than the ATP-binding catalytic domain like other JAK inhibitors, deucravacitinib blocks pro-inflammatory cytokine signaling without inhibiting JAK1, JAK2, or JAK3. This selectivity helps reduce systemic immunosuppression while maintaining efficacy in autoimmune skin diseases.

• Absorption:
• Rapidly absorbed following oral administration.
• Tmax: ~2–3 hours post-dose
• Bioavailability: ~99%
• Distribution:
• Volume of distribution: ~140 L
• Plasma protein binding: ~82–90%
• Metabolism:
• Primarily metabolized by CYP1A2, CYP2B6, and CYP2D6, with minor contributions from other CYP enzymes.
• Also undergoes non-CYP-mediated hydrolysis.
• Elimination:
• Half-life: ~10 hours
• Excretion: ~38% in urine (mainly metabolites), ~30% in feces (unchanged and metabolites)

• Pregnancy:
• Not assigned a specific FDA pregnancy category under the new labeling system.
• Animal studies show fetal harm at high exposures; use only if clearly needed.
• Not recommended during pregnancy unless benefits outweigh risks.
• Lactation:
• Unknown if excreted in human milk.
• Due to potential for serious adverse effects in the nursing infant, consider risks and benefits before prescribing to breastfeeding women.

• Primary Class: Immunomodulator
• Subclass: Selective TYK2 inhibitor
• Target Class: Janus kinase family inhibitor (TYK2-selective, non-JAK1/2/3)

• Known hypersensitivity to deucravacitinib or any inactive ingredients
• Concurrent use with other JAK inhibitors, biologic immunomodulators, or potent immunosuppressants (e.g., cyclosporine)
• Active serious infections (e.g., tuberculosis, sepsis)

• Serious Infections:
• Increased risk of serious bacterial, fungal, and viral infections. Screen for latent TB prior to initiating therapy.
• Malignancy Risk:
• Although TYK2 selectivity reduces JAK-associated risks, long-term data on malignancy are limited.
• Hematologic Abnormalities:
• Monitor CBC periodically during treatment.
• Liver Function Abnormalities:
• Monitor LFTs (ALT/AST) at baseline and during treatment.
• Hypersensitivity Reactions:
• Rare, but include angioedema and anaphylaxis; discontinue if severe reaction occurs.
• Live Vaccines:
• Avoid during and shortly after treatment; immunosuppressive potential may blunt vaccine response.

Common (≥2%):

• Respiratory: Nasopharyngitis, upper respiratory tract infection
• Gastrointestinal: Diarrhea, nausea
• Skin: Rash, acne
• Others: Headache, back pain

Less Common (0.1–2%):

• Folliculitis
• Elevated transaminases (ALT/AST)
• Herpes zoster reactivation (especially in older adults)

Serious or Rare (<0.1%):

• Severe infections (e.g., pneumonia, cellulitis)
• Hypersensitivity reactions
• New or worsening autoimmune conditions (e.g., lupus-like syndromes)
• Opportunistic infections (rare)

• CYP1A2 and CYP2B6 substrates:
• Deucravacitinib is a weak inhibitor; monitor for enhanced effects of sensitive substrates (e.g., theophylline, bupropion).
• Immunosuppressants (e.g., methotrexate, biologics):
• Avoid combination due to additive immunosuppressive effects and increased infection risk.
• Live vaccines:
• Contraindicated due to immunomodulatory effects.
• Alcohol and Food:
• No significant interaction; may be taken with or without food.
• CYP Inhibition/Induction:
• Not a significant inducer or inhibitor of CYP enzymes at therapeutic doses.

• FDA Approval (2022):
• Approved as the first-in-class TYK2 inhibitor for moderate to severe plaque psoriasis.
• AAD/NPF Guidelines (2023):
• Included as a recommended systemic option for patients who are candidates for oral non-biologic agents, particularly when biologics are contraindicated.
• EMA Review (2023–2024):
• EMA has initiated review for possible approval in the European Union.
• Ongoing Trials (2025):
• Investigational use in SLE and psoriatic arthritis ongoing in phase III trials.

• Temperature: Store at 20°C to 25°C (68°F to 77°F)
• Humidity: Protect from excessive moisture
• Light: Store in original container, away from direct light
• Handling Instructions:
• Keep in a tightly closed container
• Do not use past expiration date
• Keep out of reach of children