TREMFYA Solution for injection Ref.[8930] Active ingredients: Guselkumab

Traceability

In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.

Infections

Tremfya may increase the risk of infection. Treatment with Tremfya should not be initiated in patients with any clinically important active infection until the infection resolves or is adequately treated.

Patients treated with Tremfya should be instructed to seek medical advice if signs or symptoms of clinically important chronic or acute infection occur. If a patient develops a clinically important or serious infection or is not responding to standard therapy, the patient should be monitored closely and Tremfya should be discontinued until the infection resolves.

Pre-treatment evaluation for tuberculosis

Prior to initiating treatment with Tremfya, patients should be evaluated for tuberculosis (TB) infection. Patients receiving Tremfya should be monitored for signs and symptoms of active TB during and after treatment. Anti-TB therapy should be considered prior to initiating Tremfya in patients with a past history of latent or active TB in whom an adequate course of treatment cannot be confirmed.

Hypersensitivity

Serious hypersensitivity reactions have been reported in the post-marketing setting. Some cases occurred several days after treatment with guselkumab, including cases with urticaria and dyspnoea. If a serious hypersensitivity reaction occurs, administration of Tremfya should be discontinued immediately and appropriate therapy initiated.

Immunisations

Prior to initiating therapy with Tremfya, completion of all appropriate immunisations should be considered according to current immunisation guidelines. Live vaccines should not be used concurrently in patients treated with Tremfya. No data are available on the response to live or inactive vaccines.

Before live viral or live bacterial vaccination, treatment with Tremfya should be withheld for at least 12 weeks after the last dose and can be resumed at least 2 weeks after vaccination. Prescribers should consult the Summary of Product Characteristics of the specific vaccine for additional information and guidance on concomitant use of immunosuppressive agents post-vaccination.

Interactions with CYP450 substrates

In a Phase 1 study in subjects with moderate to severe plaque psoriasis, changes in systemic exposures (C_max and AUC_inf) of midazolam, S-warfarin, omeprazole, dextromethorphan, and caffeine after a single dose of guselkumab were not clinically relevant, indicating that drug interactions between guselkumab and substrates of various CYP enzymes (CYP3A4, CYP2C9, CYP2C19, CYP2D6, and CYP1A2) are unlikely. There is no need for dose adjustment when co-administering guselkumab and CYP450 substrates.

Concomitant immunosuppressive therapy or phototherapy

The safety and efficacy of Tremfya in combination with immunosuppressants, including biologics, or phototherapy have not been evaluated.

Women of childbearing potential

Women of childbearing potential should use effective methods of contraception during treatment and for at least 12 weeks after treatment.

Pregnancy

There are no data from the use of guselkumab in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonic/foetal development, parturition or postnatal development (see section 5.3). As a precautionary measure, it is preferable to avoid the use of Tremfya in pregnancy.

Breast-feeding

It is unknown whether guselkumab is excreted in human milk. Human IgGs are known to be excreted in breast milk during the first few days after birth, and decrease to low concentrations soon afterwards; consequently, a risk to the breast-fed infant during this period cannot be excluded. A decision should be made whether to discontinue, or abstain from initiating treatment with Tremfya, taking into account the benefit of breast-feeding to the child and the benefit of Tremfya therapy to the woman. See section 5.3 for information on the excretion of guselkumab in animal (cynomolgus monkey) milk.

Fertility

The effect of guselkumab 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).

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

Summary of the safety profile

The most common adverse drug reaction (ADR) was upper respiratory infection.

Tabulated list of adverse reactions

Table 1 provides a list of adverse reactions from psoriasis clinical studies as well as from post-marketing experience. The adverse reactions are classified by MedDRA System Organ Class and frequency, using the following convention: 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:

Infections and infestations

Very common: Upper respiratory infections

Common: Gastroenteritis

Common: Herpes simplex infections

Common: Tinea infections

Immune system disorders

Uncommon: Hypersensitivity

Nervous system disorders

Common: Headache

Gastrointestinal disorders

Common: Diarrhoea

Skin and subcutaneous tissue disorders

Common: Urticaria

Uncommon: Rash

Musculoskeletal and connective tissue disorders

Common: Arthralgia

General disorders and administration site conditions

Common: Injection site erythema

Uncommon: Injection site pain

Description of selected adverse reactions

Gastroenteritis

In two phase III clinical studies through the placebo-controlled period, gastroenteritis occurred more frequently in the Tremfya-treated group (1.1%) than in the placebo group (0.7%). Through Week 156, 4.9% of all Tremfya-treated patients reported gastroenteritis. Adverse reactions of gastroenteritis were non-serious and did not lead to discontinuation of Tremfya through Week 156.

Injection site reactions

In two phase III clinical studies through Week 48, 0.7% of Tremfya injections and 0.3% of placebo injections were associated with injection site reactions. Through Week 156, 0.5% of Tremfya injections were associated with injection site reactions. Adverse reactions of injection site erythema and injection site pain were generally mild to moderate in severity; none were serious, and none led to discontinuation of Tremfya.

Immunogenicity

The immunogenicity of Tremfya was evaluated using a sensitive and drug-tolerant immunoassay. In pooled phase II and phase III analyses, fewer than 6% of patients treated with Tremfya developed antidrug antibodies in up to 52 weeks of treatment. Of the patients who developed antidrug antibodies, approximately 7% had antibodies that were classified as neutralizing, which equates to 0.4% of all patients treated with Tremfya. In pooled phase III analyses, approximately 9% of patients treated with Tremfya developed antidrug antibodies in up to 156 weeks of treatment. Antidrug antibodies were not associated with lower efficacy or development of injection-site reactions.

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.

In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.