Source: European Medicines Agency (EU) Revision Year: 2023 Publisher: STADA Arzneimittel AG, Stadastrasse 2-18, 61118 Bad Vilbel, Germany
Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.
Patients with severe hepatic impairment (Child-Pugh Class C).
When glucocorticosteroids are used chronically, systemic effects such as hypercorticism and adrenal suppression may occur. Glucocorticosteroids can reduce the response of the hypothalamus-pituitary-adrenal (HPA) axis to stress. In situations where patients are subject to surgery or other stress situations, supplementation with a systemic glucocorticosteroid is recommended.
Since Kinpeygo contains a glucocorticosteroid, general warnings concerning glucocorticosteroids, as given below, should be followed.
Patients with moderate or severe hepatic impairment (Child-Pugh Class B or C respectively) could be at an increased risk of hypercorticism and adrenal axis suppression due to an increased systemic exposure of oral budesonide. Patients with moderate hepatic impairment (Child-Pugh Class B) should be monitored for increased signs and/or symptoms of hypercorticism.
Patients who are transferred from glucocorticosteroid treatment with high systemic availability to glucocorticosteroids with lower systemic availability, such as budesonide, should be monitored since symptoms attributed to withdrawal of steroid therapy, including those of acute adrenal axis suppression or benign intracranial hypertension, may develop. Adrenocortical function monitoring may be required in these patients and the dose of glucocorticosteroid treatment with high systemic effects should be reduced cautiously.
Replacement of systemic glucocorticosteroids with budesonide may unmask allergies (e.g., rhinitis and eczema), which were previously controlled by the systemic medicinal product.
Patients who are on medicinal products that suppress the immune system are more susceptible to infection than healthy individuals. Chickenpox and measles, for example, can have a more serious or even fatal course in susceptible patients or patients on immunosuppressant doses of glucocorticosteroids. In patients who have not had these diseases, particular care should be taken to avoid exposure.
How the dose, route, and duration of glucocorticosteroid administration affect the risk of developing a disseminated infection is not known. The contribution of the underlying disease and/or prior glucocorticosteroid treatment to the risk is also not known. If exposed to chickenpox, therapy with varicella zoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG), as appropriate, may be indicated. If exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See Summaries of Product Characteristics for VZIG and IG.) If chickenpox develops, treatment with antiviral agents may be considered.
Glucocorticosteroids should be used with caution, if at all, in patients with active or quiescent tuberculosis infection, untreated fungal, bacterial, systemic viral or parasitic infections, or ocular herpes simplex.
Patients with infections, hypertension, diabetes mellitus, osteoporosis, peptic ulcer, glaucoma or cataracts, or with a family history of diabetes or glaucoma, or with any other condition where use of glucocorticosteroids may be associated with an increased risk of adverse effects, should be monitored.
Visual disturbance may be reported with systemic and topical glucocorticosteroid 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 glucocorticosteroids.
Concomitant treatment with potent CYP3A4 inhibitors, including ketoconazole and cobicistat-containing products, is expected to increase the risk of systemic side effects attributable to budesonide. The combination should be avoided unless the benefit outweighs the increased risk of systemic glucocorticosteroid side effects. If this is not possible, the period between treatments should be as long as possible and a reduction of the budesonide dose to 8 mg budesonide daily could also be considered (see section 4.5).
After extensive intake of grapefruit juice (which inhibits CYP3A4 activity predominantly in the intestinal mucosa), the systemic exposure to budesonide after oral administration increased approximately two-fold. As with other medicinal products primarily metabolised through CYP3A4, regular ingestion of grapefruit or its juice should be avoided in connection with Kinpeygo administration (other juices such as orange juice or apple juice do not inhibit CYP3A4). See also section 4.5.
Because adrenal function may be suppressed, an ACTH stimulation test for diagnosing pituitary insufficiency might show false results (low values).
Patients with rare hereditary problems of fructose intolerance, glucose-galactose malabsorption or sucroseisomaltase insufficiency should not take this medicinal product.
Budesonide is metabolised via CYP3A4. Potent inhibitors of CYP3A4 can increase plasma levels of budesonide. Co-administration of the potent CYP3A4 inhibitor ketoconazole or intake of grapefruit juice resulted in a 6.5-fold and 2-fold increase, respectively in the bioavailability of budesonide, compared to budesonide alone.
Thus, clinically relevant interactions with potent CYP3A inhibitors, such as ketoconazole, itraconazole, ritonavir, indinavir, saquinavir, erythromycin, cyclosporine, and grapefruit juice, are to be expected, and may increase systemic budesonide concentrations (see sections 4.4 and 5.2).
Concomitant treatment with CYP3A4 inducers such as carbamazepine may reduce budesonide systemic exposure.
Given its low affinity for CYP3A4 and P-gp, as well as the formulation, pharmacokinetic (PK) characteristics and low systemic exposure, Kinpeygo is unlikely to affect the systemic exposure of other medicinal products.
Oral contraceptives containing ethinyl estradiol, which are also metabolised by CYP3A4, do not affect the pharmacokinetics of budesonide.
The pharmacokinetics of budesonide have not been evaluated in combination with proton pump inhibitors (PPIs). In a study assessing intragastric and intraduodenal pH in healthy volunteers after repeated dosing with the PPI omeprazole 40 mg once daily, intragastric and intraduodenal pH did not exceed that required for disintegration of Kinpeygo. Beyond the duodenum, PPIs such as omeprazole are unlikely to affect pH.
Budesonide treatment may reduce serum potassium, which should be considered when Kinpeygo is coadministered with a medicinal product where the pharmacological effects may be potentiated by low serum potassium, such as cardiac glucosides, or when co-administered with diuretics that lower serum potassium.
Administration during pregnancy should be avoided unless there are compelling reasons for therapy with Kinpeygo. There are only 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 is expected to be higher in association with treatment with Kinpeygo 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.
Therefore, Kinpeygo should not be used during pregnancy unless the clinical condition of the woman requires treatment with budesonide. The expected benefits for the pregnant woman have to be weighed against the potential risk for the fetus.
Budesonide was found to cross the placental barrier. The relevance of this observation to humans has not been established.
Hypoadrenalism may occur in neonates exposed to glucocorticosteroids in utero; carefully observe neonates for signs and symptoms of hypoadrenalism.
Budesonide is excreted in breast milk.
Lactation studies have not been conducted with oral budesonide, including Kinpeygo, and no information is available on the effects of the medicinal product on the breast-fed infant or the effects of the medicinal product on milk production. A risk to the breast-fed infant cannot be excluded.
If Kinpeygo is used when a mother is breast-feeding, a decision must be made whether to discontinue breastfeeding 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.
There are no data on the effect of budesonide on human fertility. There were no effects on fertility in rats after treatment with budesonide.
No studies on the effects of Kinpeygo on the ability to drive and use machines have been performed. It is expected that Kinpeygo has no or negligible influence on the ability to drive or use machinery.
In the Kinpeygo phase 3 clinical study the most commonly reported adverse drug reactions were acne reported in approximately 10% of patients, hypertension, peripheral oedema, face oedema, and dyspepsia, each occurring in approximately 5% of patients; these were mainly of mild or moderate severity and reversible, reflecting the low systemic exposure to budesonide after oral administration.
Adverse drug reactions reported in the pivotal phase 3 clinical study with Kinpeygo are presented in Table 1.
Adverse reactions reported are listed according to the following frequency: 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).
Table 1. Adverse drug reactions by frequency and system organ class (SOC):
| MedDRA system organ classification | Frequency | Reaction |
|---|---|---|
| Endocrine disorders | Common | Cushingoid features |
| Metabolism and nutrition disorders | Common | Diabetes mellitus* |
| Eye disorders | Rare | Vision, blurred (see also section 4.4) |
| Vascular disorders | Common | Hypertension |
| Gastrointestinal disorders | Common | Dyspepsia |
| Skin and subcutaneous tissue disorders | Common | Skin reactions (acne, dermatitis) |
| Musculoskeletal and connective tissue disorders | Common | Muscle spasms |
| General disorders and administration site conditions | Common | Edema peripheral Weight increased |
* All patients with new onset of diabetes diagnosed during or following Kinpeygo treatment had levels of FBG and HbA1c prior to the start of treatment that were indicative of pre-diabetes (HbA1c ≥5.7% or FBG≥100 mg/dL).
Adverse drug reactions typical of systemic glucocorticosteroids may occur (e.g., cushingoid features, increased blood pressure, increased risk of infection, delayed wound healing, reduced glucose tolerance, sodium retention with oedema formation, muscle weakness, osteoporosis, glaucoma, mental disorders, peptic ulcer, increased risk of thrombosis). These adverse drug reactions are dependent on dose, treatment time, concomitant and previous glucocorticosteroid intake, and individual sensitivity. Not all of these adverse reactions were observed in the clinical study program of Kinpeygo.
No data available.
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.
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