JORVEZA Oral suspension Ref.[116525] 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 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 cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids.

Growth and monitoring

It is recommended that the height of children receiving prolonged treatment with budesonide is regularly monitored. If growth is slowed, the benefits of corticosteroid treatment and the potential risks of growth impairment should be considered carefully. If it is decided to continue budesonide treatment, the dose should be reduced to the lowest dose at which effective control of the disease is maintained.

Effects on the hypothalamic–pituitary–adrenal (HPA) axis

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

CYP3A4 inhibitors

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

Interference with ACTH stimulation test

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

Information about excipients

Sodium

This medicinal product contains less than 1 mmol sodium (23 mg) per mL of oral suspension, that is to say essentially 'sodium-free'.

Sodium benzoate

This medicinal product contains 0.86 mg sodium benzoate in each mL of oral suspension.

Sucrose

This medicinal product contains 100 mg sucrose in each mL of oral suspension. Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucrase-isomaltase insufficiency should not take this medicinal product. Sucrose may be harmful to the teeth.

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 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).

This medicinal product has no or negligible influence on the ability to drive and use machines.

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).

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.