JORVEZA Orodispersible tablet Ref.[116522] Active ingredients: Budesonide

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 considered for referral to an ophthalmologist for evaluation of possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.

Others

Glucocorticosteroids may cause suppression of the hypothalamic–pituitary–adrenal (HPA) axis and reduce the stress response. When patients are subject to surgery or other stresses, supplementary systemic glucocorticosteroid treatment is therefore recommended.

Concomitant treatment with ketoconazole or other CYP3A4 inhibitors should be avoided (see section 4.5).

Interference with serological testing

Because adrenal function may be suppressed by treatment with budesonide, an ACTH stimulation test for diagnosing pituitary insufficiency might show false results (low values).

Sodium content

Jorveza 0.5 mg and 1 mg orodispersible tablets contain 52 mg of sodium per daily dose, equivalent to 2.6% of the WHO recommended maximum daily intake of 2 g sodium for an adult.

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.

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 inhumans. 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).

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

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).

The following known adverse reactions of the therapeutic class (corticosteroids, budesonide) could also occur with Jorveza (frequency = not known).

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.