Jorveza · 4.1 Therapeutic indications · 2

HOS-098519 · has-adverse-reaction-information · PDF-Seite 6

Summary of the safety profile Fungal infections in the mouth, pharynx and the oesophagus were the most frequently observed adverse reactions in clinical studies with Jorveza. In the clinical studies BUL-1/EEA and BUL-2/EER, a total of 44 out of 268 patients (16.4%) exposed to Jorveza experienced cases of suspected fungal infections associated with clinical symptoms, which were all of mild or moderate intensity. The total number of infections (including those diagnosed by endoscopy and histology without symptoms) was 92, occurring in 72 out of 268 patients (26.9%). Long-term treatment with Jorveza of up to 3 years (48-weeks in the BUL-2/EER followed by 96-week open-label treatment) did not increase the rate of side effects including local candidiasis. Tabulated list of adverse reactions Adverse reactions observed in clinical studies with Jorveza are listed in the table below, by MedDRA system organ class and 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) or not known (cannot be estimated from the available data). MedDRA Very common Common Uncommon system organ class Infections and Esophageal candidiasis, Nasopharyngitis, infestations oral and/or pharyngitis oropharyngeal candidiasis Immune system Angioedema disorders Psychiatric Sleep disorder anxiety, agitation disorders Nervous system Headache, dysgeusia Dizziness disorders Eye disorders Dry eyes 6  Vascular Hypertension disorders Respiratory, Cough, dry throat, thoracic and oropharyngeal pain mediastinal disorders Gastrointestinal Gastroesophageal reflux Abdominal pain, disorders disease, nausea, oral abdominal distension, paraesthesi

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HOS-098525 · has-adverse-reaction-information · PDF-Seite 17

Summary of the safety profile Children and adolescents 2 to 17 years of age In the paediatric clinical study PEDEOS 1 (BUU-5/EEA) with budesonide 0.2 mg/mL oral suspension, local fungal infection (candidiasis, clinically manifested or confirmed by histology) occurred in 8.0% of patients across all budesonide dosage groups, with no dose effect. All cases were non-serious, generally of mild intensity, did not generally interfere with normal daily activities, and did not impact the treatment effect. Adults 18 years and older Fungal infections in the mouth, pharynx and the oesophagus were the most frequently observed adverse reactions in clinical studies with Jorveza 0.5 mg and 1 mg orodispersible tablets. In the clinical studies BUL-1/EEA and BUL-2/EER, a total of 44 out of 268 adult patients (16.4%) exposed to the orodispersible tablets experienced cases of suspected fungal infections associated with clinical symptoms, which were all of mild or moderate intensity. The total number of infections (including those diagnosed by endoscopy and histology without symptoms) was 92, occurring in 72 out of 268 patients (26.9%). Long-term treatment with budesonide orodispersible tablets of up to 3 years (48- weeks in the BUL-2/EER followed by 96-week open-label treatment) did not increase the rate of side effects including local candidiasis. Tabulated list of adverse reactions Adverse reactions observed in clinical studies with budesonide 0.5 mg and 1 mg orodispersible tablets and 0.2 mg/mL oral suspension are listed in the table below, by MedDRA system organ class and 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) or not known (cannot be estimated from the available data). MedDRA Very common Common Uncommon system organ class Infections and Esophageal candidiasis, Nasopharyngitis, infestations oral and/or pharyngitis oropharyngeal candidiasis Immune system Angioedema disorders Psychiatric Sleep disorder Anxiety, agitation disorders Nervous system Headache, dysgeusia Dizziness disorders Eye disorder

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HOS-098521 · has-contraindication-information · PDF-Seite 14

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-098515 · has-contraindication-information · PDF-Seite 4

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-098520 · has-indication-information · PDF-Seite 12

Jorveza 0.2 mg/mL oral suspension is indicated for the treatment of eosinophilic esophagitis (EoE) in paediatric patients 2 to 17 years of age.

HOS-098514 · has-indication-information · PDF-Seite 2

Jorveza is indicated for the treatment of eosinophilic esophagitis (EoE) in adults (older than 18 years of age).

HOS-098523 · has-interaction-information · PDF-Seite 15

CYP3A4 inhibitors Co-treatment with potent CYP3A inhibitors such as ketoconazole, ritonavir, itraconazole, clarithromycin, cobicistat and grapefruit juice may cause a marked increase of the plasma concentration of budesonide and is expected to increase the risk of systemic adverse reactions. Therefore, concomitant use should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid adverse reactions, in which case patients should be monitored for systemic corticosteroid adverse reactions. Ketoconazole 200 mg once daily orally increased the plasma concentration of budesonide (3 mg single dose) approximately 6-fold during concomitant administration. When ketoconazole was administered approximately 12 hours after budesonide, the plasma concentration of budesonide increased approximately 3-fold. 15 Oestrogens, oral contraceptives Elevated plasma concentrations and enhanced effects of glucocorticosteroids have been reported in women also receiving oestrogens or oral contraceptives. No such effect has been observed with budesonide and concomitant intake of low-dose combination oral contraceptives. Cardiac glycosides The action of glycoside can be potentiated by potassium deficiency which is a potential and known adverse reaction of glucocorticoids. Saluretics Concommitant use of glucocorticoids may result in enhanced potassium excretion and aggravated hypokalaemia.

HOS-098517 · has-interaction-information · PDF-Seite 5

CYP3A4 inhibitors Co-treatment with potent CYP3A inhibitors such as ketoconazole, ritonavir, itraconazole, clarithromycin, cobicistat and grapefruit juice may cause a marked increase of the plasma concentration of budesonide and is expected to increase the risk of systemic adverse reactions. Therefore, concomitant use should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid adverse reactions, in which case patients should be monitored for systemic corticosteroid adverse reactions. Ketoconazole 200 mg once daily orally increased the plasma concentration of budesonide (3 mg single dose) approximately 6-fold during concomitant administration. When ketoconazole was administered approximately 12 hours after budesonide, the plasma concentration of budesonide increased approximately 3-fold. Oestrogens, oral contraceptives Elevated plasma concentrations and enhanced effects of glucocorticosteroids have been reported in women also receiving oestrogens or oral contraceptives. No such effect has been observed with budesonide and concomitant intake of low-dose combination oral contraceptives. Cardiac glycosides The action of glycoside can be potentiated by potassium deficiency which is a potential and known adverse reaction of glucocorticoids. Saluretics Concommitant use of glucocorticoids may result in enhanced potassium excretion and aggravated hypokalaemia.

HOS-098518 · has-pregnancy-information · PDF-Seite 5

Pregnancy Administration during pregnancy should be avoided unless there are compelling reasons for therapy with Jorveza. There are few data of pregnancy outcomes after oral administration of budesonide in 5 humans. Although data on the use of inhaled budesonide in a large number of exposed pregnancies indicate no adverse effect, the maximal concentration of budesonide in plasma has to be expected to be higher in the treatment with Jorveza compared to inhaled budesonide. In pregnant animals, budesonide, like other glucocorticosteroids, has been shown to cause abnormalities of fetal development (see section 5.3). The relevance of this to man has not been established. Breast-feeding Budesonide is excreted in human milk (data on excretion after inhalative use is available). However, only minor effects on the breast-fed child are anticipated after oral use of Jorveza within the therapeutic range. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from Jorveza therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility There are no data on the effect of budesonide on human fertility. Fertility was unaffected following budesonide treatment in animal studies (see section 5.3).

HOS-098524 · has-pregnancy-information · PDF-Seite 16

Pregnancy Administration during pregnancy should be avoided unless there are compelling reasons for therapy with budesonide. There are few data of pregnancy outcomes after oral administration of budesonide in humans. Although data on the use of inhaled budesonide in a large number of exposed pregnancies indicate no adverse effect, the maximal concentration of budesonide in plasma has to be expected to be higher in the treatment with Jorveza compared to inhaled budesonide. In pregnant animals, budesonide, like other glucocorticosteroids, has been shown to cause abnormalities of fetal development (see section 5.3). The relevance of this to man has not been established. Breast-feeding Budesonide is excreted in human milk (data on excretion after inhalative use is available). However, only minor effects on the breast-fed child are anticipated after oral use of budesonide within the therapeutic range. A decision must be made whether to discontinue breast-feeding or to discontinue/abstain from budesonide therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman. Fertility There are no data on the effect of budesonide on human fertility. Fertility was unaffected following budesonide treatment in animal studies (see section 5.3).

HOS-098516 · has-warning-information · PDF-Seite 4

Infections Suppression of the inflammatory response and immune function increases the susceptibility to infections and their severity. Symptoms of infections can be atypical or masked. In clinical studies conducted with Jorveza oral, oropharyngeal and esophageal candida infections have been observed with a high frequency (see section 4.8). If indicated, symptomatic candidiasis of the mouth and throat can be treated with topical or systemic anti-fungal therapy whilst still continuing treatment with Jorveza. Chickenpox, herpes zoster and measles can have a more serious course in patients treated with glucocorticosteroids. In patients who have not had these diseases, the vaccination status should be checked, and particular care should be taken to avoid exposure. Vaccines The co-administration of live vaccines and glucocorticosteroids should be avoided as this is likely to reduce the immune response to vaccines. The antibody response to other vaccines may be diminished. Special populations Patients with tuberculosis, hypertension, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma, cataract, family history of diabetes or family history of glaucoma may be at higher risk of experiencing systemic glucocorticosteroid adverse reactions (see below and section 4.8) and should therefore be monitored for the occurrence of such effects. Reduced liver function may affect the elimination of budesonide, causing higher systemic exposure. The risk of adverse reactions (systemic glucocorticosteroid effects) will be increased. However, no systematic data are available. Patients with hepatic impairment should therefore not be treated. Systemic effects of glucocorticosteroids Systemic effects of glucocorticosteroids (e.g., Cushing’s syndrome, adrenal suppression, growth retardation, cataract, glaucoma, decreased bone mineral density and a wide range of psychiatric effects) may occur (see also section 4.8). These adverse reactions depend on the duration of treatment, concomitant and previous glucocorticosteroid treatment and the individual sensitivity. Angioedema Angioedema has been reported with the use of Jorveza, mostly as part of allergic reactions which included rash and itching. If signs of angioedema are observed, the treatment should be stopped. Visual disturbance Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be c

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HOS-098522 · has-warning-information · PDF-Seite 14

Infections Suppression of the inflammatory response and immune function increases the susceptibility to infections and their severity. Symptoms of infections can be atypical or masked. In clinical studies conducted with budesonide orodispersible tablets and oral suspension, the observation of oral, oropharyngeal and oesophageal candida infections has been very common. However, in a clinical study conducted with budesonide oral suspension the frequency was slightly lower (see section 4.8). If indicated, symptomatic candidiasis of the mouth and throat can be treated with topical or systemic antifungal therapy whilst still continuing treatment with budesonide oral suspension. Chickenpox, herpes zoster and measles can have a more serious course in patients treated with glucocorticosteroids. In patients who have not had these diseases, the vaccination status should be checked, and particular care should be taken to avoid exposure. Vaccines The co-administration of live vaccines and glucocorticosteroids should be avoided as this is likely to reduce the immune response to vaccines. The antibody response to other vaccines may be diminished. Systemic effects of glucocorticosteroids and concomitant diseases Systemic effects of glucocorticosteroids (e.g., Cushing’s syndrome, adrenal suppression, growth retardation, cataract, glaucoma, decreased bone mineral density and a wide range of psychiatric effects) may occur (see also section 4.8). These adverse reactions depend on the duration of treatment, concomitant and previous glucocorticosteroid treatment and the individual sensitivity. Patients with infections, hypertension, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma, cataract, family history of diabetes or family history of glaucoma may be at higher risk of experiencing systemic glucocorticosteroid adverse reactions (see below and section 4.8) and should therefore be monitored for the occurrence of such effects. Angioedema Angioedema has been reported with the use of budesonide orodispersible tablets, mostly as part of allergic reactions which included rash and itching. If signs of angioedema are observed, the treatment should be stopped. Visual disturbance Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, the patient should be considered for referral to an ophthalmologist for evaluation of possible causes which may include

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