Cibinqo · 4.3 Contraindications · 1

HOS-099693 · has-adverse-reaction-information · PDF-Seite 11

Summary of the safety profile The most commonly reported adverse reactions are nausea (15.1%), headache (7.9%), acne (4.8%), herpes simplex (4.2%), blood creatine phosphokinase increased (3.8%), vomiting (3.5%), dizziness (3.4%) and abdominal pain upper (2.2%). The most frequent serious adverse reactions are infections (0.3%) (see section 4.4). Tabulated list of adverse reactions A total of 3 850 patients were treated with abrocitinib in clinical studies in atopic dermatitis. Among them 3 052 patients (representing 7 059.5 patient-years of exposure) were integrated for safety analysis. The integrated safety analysis included 1 999 patients receiving a constant dose of abrocitinib 200 mg and 1 053 patients receiving a constant dose of 100 mg. There were 2 017 patients with at least 48 weeks of exposure. Five placebo-controlled studies were integrated (703 patients on 100 mg once daily, 684 patients on 200 mg once daily and 438 patients on placebo) to evaluate the safety of abrocitinib in comparison to placebo for up to 16 weeks. Listed in Table 2 are adverse reactions observed in atopic dermatitis clinical 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. 11  Table 2. Adverse reactions System organ class Very common Common Uncommon Infections and infestations Herpes simplexa Pneumonia Herpes zosterb Blood and lymphatic system Thrombocytopenia disorders Lymphopenia Neutropeniac Metabolism and nutrition Hyperlipidaemiad disorders Nervous system disorders Headache Dizziness Vascular disorders

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HOS-099689 · has-contraindication-information · PDF-Seite 5

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. • Active serious systemic infections, including tuberculosis (TB) (see section 4.4). • Severe hepatic impairment (see section 4.2). • Pregnancy and breast-feeding (see section 4.6). 5

HOS-099688 · has-indication-information · PDF-Seite 3

Cibinqo is indicated for the treatment of moderate-to-severe atopic dermatitis in adults and adolescents 12 years and older who are candidates for systemic therapy.

HOS-099691 · has-interaction-information · PDF-Seite 9

Potential for other medicines to affect pharmacokinetics of abrocitinib Abrocitinib is metabolised predominantly by CYP2C19 and CYP2C9 enzymes, and to a lesser extent by CYP3A4 and CYP2B6 enzymes, and its active metabolites are renally excreted and are substrates of the organic anion transporter 3 (OAT3). Therefore, exposures of abrocitinib and/or its active metabolites may be affected by medicinal products that inhibit or induce these enzymes and transporter. Dose adjustments, as appropriate, are outlined in section 4.2. Co-administration with CYP2C19/CYP2C9 inhibitors When 100 mg abrocitinib was administered concomitantly with fluvoxamine (a strong CYP2C19 and moderate CYP3A inhibitor) or fluconazole (a strong CYP2C19, moderate CYP2C9 and CYP3A inhibitor), the extent of exposure of abrocitinib active moiety (see section 5.2) increased by 91% and 155%, respectively, compared with administration alone (see section 4.2). Co-administration with CYP2C19/CYP2C9 inducers Administration of 200 mg abrocitinib after multiple doses with rifampicin, a strong inducer of CYP enzymes, resulted in reduction of abrocitinib active moiety exposures by approximately 56% (see section 4.2). 9 Co-administration with OAT3 inhibitors When abrocitinib 200 mg was administered concomitantly with probenecid, an OAT3 inhibitor, abrocitinib active moiety exposures increased by approximately 66%. This is not clinically significant, and a dose adjustment is not needed. Co-administration with products which increase gastric pH When abrocitinib 200 mg was administered concomitantly with famotidine 40 mg, an H2-receptor antagonist, abrocitinib active moiety exposures decreased by approximately 35%. The effect of elevating gastric pH with antacids, or proton pump inhibitors (omeprazole) on the pharmacokinetics of abrocitinib has not been studied and may be similar to that seen with famotidine. The higher 200 mg daily dose should be considered for patients treated concomitantly with products which increase gastric pH, as they may reduce the efficacy of abrocitinib. Potential for abrocitinib to affect pharmacokinetics of other medicinal products No clinically significant effects of abrocitinib were observed in interaction studies with oral contraceptives (e.g. ethinyl oestradiol/levonorgestrel). In vitro, abrocitinib is an inhibitor of P glycoprotein (P-gp). Co-administration of dabigatran etexilate (a P-gp substrate), with a s

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HOS-099692 · has-pregnancy-information · PDF-Seite 10

Women of childbearing potential Women of reproductive potential should be advised to use effective contraception during treatment and for 1 month following the final dose of Cibinqo. Pregnancy planning and prevention for females of reproductive potential should be encouraged. Pregnancy There are no or limited amount of data on the use of abrocitinib in pregnant women. Studies in animals have shown reproductive toxicity. Abrocitinib has been shown to cause embryo-foetal lethality in pregnant rats and rabbits, skeletal variations in the foetuses of pregnant rats and rabbits, and to affect parturition and peri/postnatal development in rats (see section 5.3). Cibinqo is contraindicated during pregnancy (see section 4.3). 10 Breast-feeding There are no data on the presence of abrocitinib in human milk, the effects on the breast-fed infant, or the effects on milk production. Abrocitinib was secreted in milk of lactating rats. A risk to newborns/infants cannot be excluded and Cibinqo is contraindicated during breast-feeding (see section 4.3). Fertility Based on the findings in rats, oral administration of Cibinqo may result in temporary reduced fertility in females of reproductive potential. The effects on female rat fertility were reversible 1 month after cessation of abrocitinib oral administration (see section 5.3).

HOS-099690 · has-warning-information · PDF-Seite 6

Abrocitinib 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) Infections/serious infections Serious infections have been reported in patients receiving abrocitinib. The most frequent serious infections in clinical studies were herpes simplex, herpes zoster and pneumonia (see section 4.8). As there is a higher incidence of infections in the elderly and in the diabetic populations in general, caution should be used when treating the elderly and patients with diabetes. In patients 65 years of age and older, abrocitinib should only be used if no suitable treatment alternatives are available (see section 4.2). Treatment must not be initiated in patients with an active, serious systemic infection (see section 4.3). Risks and benefits of treatment prior to initiating abrocitinib should be considered for patients: • with chronic or recurrent infection • who have been exposed to TB • with a history of a serious or an opportunistic infection • who have resided or travelled in areas of endemic TB or endemic 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 abrocitinib. A patient who develops a new infection during treatment should undergo prompt and complete diagnostic testing and appropriate antimicrobial therapy should be initiated. The patient should be closely monitored and therapy should be temporarily interrupted if the patient is not responding to standard therapy. Tuberculosis Tuberculosis was observed in clinical studies with abrocitinib. Patients should be screened for TB before starting treatment and yearly screening for patients in highly endemic areas for TB should be considered. Abrocitinib must not be given to patients with active TB (see section 4.3). For patients with a new diagnosis of latent TB or prior untreated latent TB, preventive therapy for latent TB should be started prior to initiation of treatment. Viral reactivation Viral reactivation, including herpes virus reactivation (e.g. herpes zoster, herpes simplex), was reported in clinical studies (see section 4.8).

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