Litfulo · 4.3 Contraindications · 1

HOS-100409 · has-adverse-reaction-information · PDF-Seite 8

Summary of the safety profile The most frequently reported adverse reactions are diarrhoea (9.2%), acne (6.2%), upper respiratory tract infections (6.2%), urticaria (4.6%), rash (3.8%), folliculitis (3.1%), and dizziness (2.3%). Tabulated list of adverse reactions A total of 1630 patients were treated with ritlecitinib representing 3751 patient-years of exposure. Three placebo-controlled studies were integrated (130 participants on 50 mg daily and 213 participants on placebo) to evaluate the safety of ritlecitinib in comparison to placebo for up to 24 weeks after treatment initiation. Table 2 lists all adverse reactions observed in alopecia areata placebo-controlled studies presented by system organ class and frequency, using the following categories: 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). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. Table 2. Adverse reactions System organ class Common Uncommon Infections and infestations Herpes zoster Folliculitis Upper respiratory tract infections Nervous system disorders Dizziness Gastrointestinal disorders Diarrhoea Skin and subcutaneous tissue Acne disorders Urticaria Rash Investigations Blood creatine phosphokinase Platelet count decreased increased Lymphocyte count decreased Alanine aminotransferase increased ˃ 3 × ULNa Aspartate aminotransferase increased ˃ 3 × ULNa a. Includes changes detected during laboratory monitoring Description of selected adverse reactions Infections In the placebo-controlled studies, for up to 24 weeks, overall infections have been reported in 31% of patients (80.35 per 100 patient-years) tr

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HOS-100405 · has-contraindication-information · PDF-Seite 4

• Hypersensitivity to the active substance(s) or to any of the excipients listed in section 6.1. • Active serious infections, including tuberculosis (TB) (see section 4.4). • Severe hepatic impairment (see section 4.2). • Pregnancy and breast-feeding (see section 4.6).

HOS-100404 · has-indication-information · PDF-Seite 2

Litfulo is indicated for the treatment of severe alopecia areata in adults and adolescents 12 years of age and older (see section 5.1).

HOS-100407 · has-interaction-information · PDF-Seite 6

Potential for other medicinal products to affect the pharmacokinetics of ritlecitinib The coadministration of multiple 200 mg doses of itraconazole, a strong CYP3A inhibitor, increased the area under curve (AUC)inf of ritlecitinib by approximately 15%. This is not considered clinically significant and, therefore dose adjustment is not required when ritlecitinib is coadministered with CYP3A inhibitors. 6 The coadministration of multiple 600 mg doses of rifampicin, a strong inducer of CYP enzymes, decreased the AUCinf of ritlecitinib by approximately 44%. This is not considered clinically significant and, therefore dose adjustment is not required when ritlecitinib is coadministered with inducers of CYP enzymes. Potential for ritlecitinib to affect the pharmacokinetics of other medicinal products Multiple doses of 200 mg once daily ritlecitinib increased the AUCinf and Cmax of midazolam a CYP3A4 substrate, by approximately 2.7-fold and 1.8-fold, respectively. Ritlecitinib is a moderate inhibitor of CYP3A; caution should be exercised with concomitant use of ritlecitinib with CYP3A substrates (e.g., quinidine, cyclosporine, dihydroergotamine, ergotamine, pimozide) where moderate concentration changes may lead to serious adverse reactions. Dose adjustment recommendations for the CYP3A substrate (e.g., colchicine, everolimus, tacrolimus, sirolimus) should be considered. Multiple doses of 200 mg once daily ritlecitinib increased the AUCinf and Cmax of caffeine, a CYP1A2 substrate, by approximately 2.7-fold and 1.1-fold, respectively. Ritlecitinib is a moderate inhibitor of CYP1A2; caution should be exercised with concomitant use of ritlecitinib with other CYP1A2 substrates (e.g., tizanidine) where moderate concentration changes may lead to serious adverse reactions. Dose adjustment recommendations for the CYP1A2 substrate (e.g., theophylline, pirfenidone) should be considered. The coadministration of a single 400 mg dose of ritlecitinib increased the AUCinf of sumatriptan (an organic cation transporter [OCT]1 substrate) by approximately 1.3 to 1.5-fold relative to sumatriptan dose given alone. The increase in sumatriptan exposure is not considered clinically relevant. Caution should be exercised with concomitant use of ritlecitinib with OCT1 substrates where small concentration changes may lead to serious adverse reactions. Ritlecitinib did not produce clinically significant changes in the exposures of o

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HOS-100408 · has-pregnancy-information · PDF-Seite 7

Women of childbearing potential Ritlecitinib is not recommended in women of childbearing potential not using contraception. Women of childbearing potential have to use effective contraception during treatment and for 1 month following the final dose of Litfulo. Pregnancy There are no or limited data from the use of ritlecitinib in pregnant women. Studies in animals have shown reproductive toxicity (see section 5.3). Ritlecitinib was teratogenic in rats and rabbits at high doses (see section 5.3). Litfulo is contraindicated during pregnancy (see section 4.3). Breast-feeding Available pharmacodynamic/toxicological data in animals have shown excretion of ritlecitinib in milk (see section 5.3). A risk to newborns/infants cannot be excluded. Litfulo is contraindicated during breast-feeding (see section 4.3). 7 Fertility The effect of ritlecitinib on human fertility has not been evaluated. There were no effects on fertility in rats at clinically relevant exposures (see section 5.3).

HOS-100406 · has-warning-information · PDF-Seite 4

Ritlecitinib should only be used if no suitable treatment alternatives are available in patients: - 65 years of age and older; - patients with history of atherosclerotic cardiovascular disease or other cardiovascular risk factors (such as current or past long-time smokers); - patients with malignancy risk factors (e.g., current malignancy or history of malignancy) Serious infections Serious infections have been reported in patients receiving ritlecitinib. The most frequent serious infections have been appendicitis, COVID-19 infection (including pneumonia), and sepsis. Treatment with ritlecitinib must not be initiated in patients with an active, serious infection (see section 4.3). The risks and benefits of treatment should be considered in patients: • with chronic or recurrent infection • who have been exposed to tuberculosis (TB) • with a history of serious or an opportunistic infection • who have resided or traveled in areas of endemic TB or mycoses, or • with underlying conditions that may predispose them to infection Patients should be closely monitored for the development of signs and symptoms of infection during and after treatment with ritlecitinib. Treatment should be interrupted if a patient develops a serious or opportunistic infection. A patient who develops a new infection during treatment with ritlecitinib should undergo prompt and complete diagnostic testing appropriate for an immunocompromised patient, appropriate antimicrobial therapy should be initiated, and the patient should be closely monitored. If interrupted, ritlecitinib may be resumed once the infection is controlled. As there is a higher incidence of infections in elderly and in the diabetic population in general, caution should be exercised when treating the elderly and patients with diabetes, and particular attention paid with respect to occurrence of infections. In patients 65 years of age and older, ritlecitinib should only be used if no suitable treatment alternatives are available (see section 4.2). Tuberculosis Patients should be screened for TB before starting therapy with ritlecitinib. Ritlecitinib must not be given to patients with active TB (see section 4.3). Anti-TB therapy should be started prior to initiating therapy with ritlecitinib in patients with a new diagnosis of latent TB or previously untreated latent TB. In patients with a negative latent TB test, anti-TB therapy should still be considered before initiating treat

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