CLIPPER Gastro-resistant prolonged-release tablet Ref.[27637] Active ingredients: Beclometasone

As there are no data in patients with severe hepatic impairment, treatment with Clipper in these patients is not recommended.

There are no data in patients with hepatic or renal insufficiency, so these patients should only be treated with caution.

Use with caution in patients with tuberculosis, diabetes mellitus, gastro-duodenal ulcer, serious arterial hypertension, osteoporosis, hypoadrenalism, glaucoma and cataract.

In case of pre-existing intestinal infection, or where such infection arises during treatment, appropriate antibiotic therapy must be instituted immediately.

Clinical safety data on treatment duration of more than four weeks are not available, therefore, the use of the product for longer periods is not recommended.

After four weeks of treatment a reduction of the plasmatic levels of corticosteroids has been observed in up to 25% of patients treated with Clipper 5 mg per day. This percentage is much lower if compared to the percentage of patients treated with oral systemic corticosteroids, such as prednisolone at a dose of 40 mg per day, showing plasma cortisol levels below the normal range (76% after eight weeks of treatment, published data). This is due to the low systemic availability of the active metabolite, beclometasone-17-monopropionate (B-17-MP), after administration of Clipper 5 mg per day, which is approximately 20% compared to the intravenous dose. The effect on HPA–axis could be considered as transient and a recovery of HPA function is expected to occur after withdrawal of the drug. However, due to the lack of follow up data after the usual treatment period, careful supervision of patients' clinical symptoms is recommended.

In case of prolonged treatment, possible adverse effects related to the suppression of HPA-axis may occur (see section 4.8). The suppression of the HPA-axis can reduce the stress response. Where patients are subject to surgery or other stresses, supplementary glucocorticoids treatment is recommended.

This medicinal product contains lactose. Patients with rare hereditary problems of galactose intolerance, total lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Patients and/or carers should be warned that potentially severe psychiatric adverse reactions may occur with systemic steroids (see section 4.8). Symptoms typically emerge within a few days or weeks of starting the treatment. Risks may be higher with high doses/systemic exposure (see also section 4.5 pharmacokinetic interactions that can increase the risk of side effects), although dose levels do not allow prediction of the onset, type, severity or duration of reactions. Most reactions recover after either dose reduction or withdrawal, although specific treatment may be necessary. Patients/carers should be encouraged to seek medical advice if worrying psychological symptoms develop, especially if depressed mood or suicidal ideation is suspected. Patients/carers should also be alert to possible psychiatric disturbances that may occur either during or immediately after dose tapering/withdrawal of systemic steroids, although such reactions have been reported infrequently.

Particular care is required when considering the use of systemic corticosteroids in patients with existing or previous history of severe affective disorders in themselves or in their first degree relatives. These would include depression or manic-depressive illness and previous steroid psychosis.

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.

No interaction studies have been performed.

As beclometasone dipropionate undergoes a very rapid metabolism via esterases enzymes without involvement of cytochrome P450, it is less dependent on CYP3A metabolism than some other corticosteroids, and in general interactions are unlikely; however, the possibility of systemic effects with concomitant use of strong CYP3A inhibitors (e.g. ritonavir, cobicistat) cannot be excluded, and therefore caution and appropriate monitoring is advised with the use of such agents.

Clipper in clinical studies has been used in conjunction with oral or rectal treatment with mesalazine. Even if no specific pharmacodynamic interactions have been studied, clinical trials did not evidence any increase of adverse events severity due to the association of BDP with 5-ASA products. In addition, according to the different pharmacokinetic pathway of the two drugs, metabolic interactions are not expected to occur.

Pregnancy

Data on a large number of exposed pregnancies indicate no adverse effects of 1 mg per day beclometasone dipropionate (after inhalation), on pregnancy or on the health of the newborn child. To date, no other relevant epidemiological data on oral administration of 5 mg beclometasone dipropionate are available. High doses of systemic corticosteroids for longer periods may cause intrauterine growth retardation.

Studies in animals have shown reproductive toxicity (see section 5.3). Clipper should not be used during pregnancy, unless strictly indicated after a careful risk/benefit evaluation. Foetal growth should be monitored.

Breast-feeding

It is not known whether beclometasone dipropionate is excreted in human milk. A risk to the newborns/infants cannot be excluded. Due to the lack of data, the administration of Clipper during lactation is not recommended unless strictly indicated after a careful risk/benefit evaluation.

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

A wide range of psychiatric reactions including affective disorders (such as irritable, euphoric, depressed and labile mood, and suicidal thoughts), psychotic reactions (including mania, delusions, hallucinations, and aggravation of schizophrenia), behavioural disturbances, irritability, anxiety, sleep disturbances, and cognitive dysfunction including confusion and amnesia have been reported with systemic corticosteroids. Reactions are common and may occur in both adults and children. In adults, the frequency of severe reactions has been estimated at 5-6%.

Psychological effects have been reported on withdrawal of corticosteroids; the frequency is not known.

The adverse reactions found during clinical studies in patients treated with 5 mg of Clipper were all classified as mild or moderate and were all uncommon (≤1/100 and >1/1000):

During clinical trials carried out with Clipper 5 mg tablets a reduction of plasma cortisol levels at the end of four weeks treatment has been observed in up to 25 % of patients, however, clinical symptoms associated with adrenal suppression have not been reported.

Particularly at high doses of systemic corticosteroids taken for long periods, rare (≤1/1000 and >1/10000) systemic adverse events may occur.

These may include:

Adverse events with frequency not known (cannot be estimated from the available data) have been identified as class risk effect of corticosteroids:

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 Yellow Card Scheme at www.mhra.gov.uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

Not applicable.