SOTYKTU Film-coated tablet Ref.[50886] Active ingredients: Deucravacitinib

Infections

Deucravacitinib may increase the risk of infections (see section 4.8).

Treatment with deucravacitinib should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated (see section 4.3). Caution should be exercised when considering the use of deucravacitinib in patients with a chronic infection or a history of recurrent infection.

Patients treated with deucravacitinib should be instructed to seek medical advice if signs or symptoms suggestive of an infection occur. If a patient develops a clinically important infection or is not responding to standard therapy, the patient should be monitored carefully and deucravacitinib should not be given until the infection resolves.

Pre-treatment evaluation for tuberculosis

Prior to initiating treatment with deucravacitinib, patients should be evaluated for tuberculosis (TB) infection. Deucravacitinib should not be given to patients with active TB (see section 4.3). Treatment of latent TB should be initiated prior to administering deucravacitinib. Anti-TB therapy should be considered prior to initiation of deucravacitinib in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed. Patients receiving deucravacitinib should be monitored for signs and symptoms of active TB.

Malignancies

Malignancies, including lymphomas and non-melanoma skin cancer (NMSC), were observed in clinical studies with deucravacitinib.

It is not known whether tyrosine kinase 2 (TYK2) inhibition may be associated with the adverse reactions of Janus Kinase (JAK) inhibition. In a large randomised active controlled study of a JAK inhibitor in rheumatoid arthritis (RA) patients 50 years and older with at least one additional cardiovascular risk factor, a higher rate of malignancies, particularly lung cancer, lymphoma and NMSC, was observed with a JAK inhibitor compared to tumour necrosis factor (TNF) inhibitors.

Limited clinical data are available to assess the potential relationship of exposure to deucravacitinib and the development of malignancies. Long-term safety evaluations are ongoing. The risks and benefits of deucravacitinib treatment should be considered prior to initiating patients.

Major adverse cardiovascular events (MACE), deep venous thrombosis (DVT) and pulmonary embolism (PE)

It is not known whether TYK2 inhibition may be associated with the adverse reactions of JAK inhibition. In a large randomised active-controlled study of a JAK inhibitor in RA patients 50 years and older with at least one additional cardiovascular risk factor, a higher rate of MACE, defined as cardiovascular death, non-fatal myocardial infarction and non-fatal stroke, and a dose dependent higher rate of venous thromboembolism including DVT and PE were observed with a JAK inhibitor compared to TNF inhibitors.

An increased risk of MACE, DVT and PE was not observed in clinical trials with deucravacitinib. Long-term safety evaluations for deucravacitinib are ongoing. The risks and benefits of deucravacitinib treatment should be considered prior to initiating patients.

Immunisations

Prior to initiating therapy with deucravacitinib, consider completion of all age-appropriate immunisations according to current immunisation guidelines. Use of live vaccines in patients being treated with deucravacitinib should be avoided. The response to live or non-live vaccines has not been evaluated.

Excipients

Lactose

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

Sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per tablet, that is to say essentially ‘sodium-free’.

Clinical studies indicate that deucravacitinib does not have clinically relevant drug interactions upon coadministration with the following other medicinal products and therefore no dose adjustments are needed.

Effect of deucravacitinib on other medicinal products

Deucravacitinib does not meaningfully impact plasma exposures of rosuvastatin (BCRP and OATP substrate), methotrexate (substrate of BCRP and renal transporters), mycophenolate mofetil (MMF) (CES1 and CES2 substrate), or oral contraceptives (norethindrone acetate and ethinyl estradiol).

Effect of other medicinal products on deucravacitinib

Medicinal products that are inhibitors or inducers of CYP enzymes or transporters such as cyclosporine (dual P-gp/breast cancer resistance protein [BCRP] inhibitor), fluvoxamine (strong CYP 1A2 inhibitor), ritonavir (moderate CYP 1A2 inducer), diflunisal (UGT 1A9 inhibitor), pyrimethamine (OCT1 inhibitor), famotidine (H2 receptor antagonist) or rabeprazole (proton pump inhibitor) do not meaningfully affect plasma deucravacitinib exposures (see section 5.2).

Pregnancy

There is a limited amount of data on the use of deucravacitinib in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity (see section 5.3). As a precautionary measure, it is preferable to avoid the use of deucravacitinib during pregnancy.

Breast-feeding

It is unknown whether deucravacitinib/metabolites are excreted in human milk. Available data in animals have shown excretion of deucravacitinib in milk (see section 5.3).

A risk to the newborns/infants by breast-feeding cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from deucravacitinib therapy taking into account the benefit of breast feeding for the child and the benefit of therapy for the woman.

Fertility

The effect of deucravacitinib on human fertility has not been evaluated. Animal studies do not indicate direct or indirect harmful effects with respect to fertility (see section 5.3).

Deucravacitinib has no or negligible influence on the ability to drive and use machines.

Summary of the safety profile

The most commonly reported adverse reaction is upper respiratory infections (18.9%), most frequently nasopharyngitis. The longer-term safety profile of deucravacitinib was similar and consistent with previous experience.

Tabulated list of adverse reactions

The following list of adverse reactions for deucravacitinib is from clinical trials in plaque psoriasis (Table 1). These reactions are presented by MedDRA System Organ Class and by frequency.

Frequencies are defined as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1,000 to <1/100); rare (≥1/10,000 to <1/1,000); very rare (<1/10,000); not known (cannot be estimated from the available data).

Table 1. List of adverse reactions:

^a Upper respiratory infections include nasopharyngitis, upper respiratory tract infection, viral upper respiratory tract infection, pharyngitis, sinusitis, acute sinusitis, rhinitis, tonsillitis, peritonsillar abscess, laryngitis, tracheitis, and rhinotracheitis.
^b Herpes simplex infections include oral herpes, herpes simplex, genital herpes, and herpes viral infection.
^c Oral ulcers include aphthous ulcer, mouth ulceration, tongue ulceration, and stomatitis.
^d Acneiform rash includes acne, dermatitis acneiform, rash, rosacea, pustule, rash pustular, and papule.

Description of selected adverse reactions

Infections

In POETYK PSO-1 and POETYK PSO-2 (see section 5.1), infections occurred in 29.1% of patients in the deucravacitinib group (116.0 events per 100 person-years) compared to 21.5% of patients in the placebo group (83.7 events per 100 person-years) during the first 16 weeks. The majority of infections were non-serious and mild to moderate in severity and did not lead to discontinuation of deucravacitinib. The incidence of serious infections in the deucravacitinib group was 0.6% (2.0 events per 100 person-years) and in the placebo group was 0.5% (1.6 events per 100 person-years).

The rate of infections in the deucravacitinib group did not increase through week 52 (95.4 events per 100 person-years). The rate of serious infections in the deucravacitinib group did not increase through week 52 (1.7 events per 100 person-years).

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.

Not applicable.