Source: Health Products Regulatory Authority (IE) Revision Year: 2023 Publisher: Cipla Europe NV, De Keyserlei 58-60, Box-19, 2018 Antwerp, Belgium
Hypersensitivity to the fluticasone or to any of the excipients listed in section 6.1.
The management of asthma should follow a stepwise programme, and patient response should be monitored clinically and by lung function tests.
Increasing use of short-acting inhaled β2-agonists to control asthma symptoms indicates deterioration of asthma control. Under these conditions, the patient’s therapy plan should be reassessed.
Sudden and progressive deterioration in asthma control is potentially life-threatening and consideration should be given to increasing corticosteroid dosage. In patients considered at risk, daily peak flow monitoring may be instituted.
Fluticasone propionate is not for use in acute asthma attacks, but for routine long-term management. Patients will require a fast-and short-acting inhaled bronchodilator to relieve acute asthmatic symptoms.
As with other inhalation therapy, paradoxical broncho spasm may occur with an immediate increase in wheezing after dosing. This should be treated immediately with fast-acting inhaled bronchodilator. Fluticasone propionate should be discontinued immediately, the patient assessed and if necessary alternative therapy instituted.
Lack of response or severe exacerbations of asthma should be treated by increasing the dose of inhaled fluticasone propionate and, if necessary, by giving a systemic steroid and/or an antibiotic if there is an infection.
An increase in the incidence of pneumonia, including pneumonia requiring hospitalisation, has been observed in patients with COPD receiving inhaled corticosteroids. There is some evidence of an increased risk of pneumonia with increasing steroid dose but this has not been demonstrated conclusively across all studies.
There is no conclusive clinical evidence for intra-class differences in the magnitude of the pneumonia risk among inhaled corticosteroid products.
Physicians should remain vigilant for the possible development of pneumonia in patients with COPD as the clinical features of such infections overlap with the symptoms of COPD exacerbations.
Risk factors for pneumonia in patients with COPD include current smoking, older age, low body mass index (BMI) and severe COPD.
Patients' inhaler technique should be checked to make sure that inhaler actuation is synchronised with inspiration to ensure optimum delivery of the drug to the lungs.
Because of the possibility of impaired adrenal response, patients transferring from oral steroid therapy to inhaled fluticasone propionate therapy should be treated with special care, and adrenocortical function regularly monitored.
Following introduction of inhaled fluticasone propionate, withdrawal of systemic therapy should be gradual and patients are encouraged to carry a steroid warning card indicating the possible need for additional therapy in times of stress.
Systemic effects may occur with any inhaled corticosteroid, particularly at high doses prescribed for long periods. These effects are much less likely to occur than with oral corticosteroids (see section 4.9). Possibles ystemic effects include Cushing’s syndrome, Cushingoid features, adrenal suppression, growth retardation in children and adolescents, decrease in bone mineral density, cataract and glaucoma and more rarely, a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children). It is important, therefore, that the dose of inhaled corticosteroid is reduced to the lowest dose at which effective control of asthma is maintained (seesection 4.8).
It is recommended that the height of children receiving prolonged treatment with inhaled corticosteroid is regularly monitored.
Certain individuals can show greater susceptibility to the effects of inhaled corticosteroid than do most patients.
Similarly replacement of systemic steroid treatment with inhaled therapy may unmask allergies suchas allergic rhinitis or eczema previously controlled by the systemic drug. These allergies should be symptomatically treated with antihistamine and/ortopical preparations, including topical steroids.
Treatment with fluticasone propionate should not be stopped abruptly.
As with all inhaled corticosteroids, special care is necessary in patients with active or quiescent pulmonary tuberculosis.
Prolonged treatment with high doses of inhaled corticosteroids may result in adrenal suppression and acute adrenal crisis. Situations, which could potentially trigger acute adrenal crisis, include trauma, surgery, infection or any rapid reduction in dosage. Presenting symptoms are typically vague and may include anorexia, abdominal pain, weight loss,tiredness, headache, nausea, vomiting, decreased level of consciousness, hypoglycaemia, and seizures. The possibility of residual impaired adrenal response should always be considered in emergency (medical or surgical) and elective situations likely to produce stress, and appropriate corticosteroid treatment considered (see section 4.9).
Adrenal function and adrenal reserve usually remain within the normal range on recommended doses of fluticasone propionat e therapy. The benefits of inhaled fluticasone propionate therapy should minimise the need for oral steroids. However, the possibility of adverse effects in patients, resulting from prior or intermittent administration of oral steroids, may persist for some time. The extent of the adrenal impairment may require specialist advice before elective procedures.
During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing’s syndrome and adrenal suppression.Therefore, concomitant use of fluticasone propionate and ritonavir should be avoided, unless the potential benefit to the patient out weighs the risk of systemic corticosteroid side-effects (see section 4.5).
There have been very rare reports of increases in blood glucose levels (see section 4.8) and this should be considered when prescribing to patients with a history of diabetes mellitus.
Visual disturbance may be reported with systemic and topical cortico steroid 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 o f 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.
Under normal circumstances, low plasma concentrations of fluticasone propionate are achieved after inhaled dosing, due to extensive first pass metabolism and high systemic clearance mediated by cytochromne P450 3A4 in the gut and liver. Hence, clinically significant drug interactions mediated by fluticasone propionate are unlikely.
A drug interaction study in healthy subjects has shown that ritonavir (a highly potent cytochrome P450 3A4 inhibitor) can greatly increase fluticasone propionate plasma concentrations, resulting in markedly reduced serum cortisol concentrations.
Co-treatment with CYP3A inhibitors, including cobicistat-containing products, is expected to increase the risk of systemic side-effects. The combination should be avoided unless the benefit outweighs the increased risk of systemic corticosteroid side-effects, in which case patients should be monitored for systemic corticosteroid side-effects.
Studies have shown that other inhibitors of cytochromne P450 3A4 produce negligible (erythromycin) and minor (ketoconazole) increases in systemic exposure to fluticasone propionate without notable reductions in serum cortisol concentrations. Nevertheless, care is advised when co-administering potent cytochromne P450 3A4 inhibitors (e.g. ketoconazole) as there is potential for increased systemic exposure to fluticasone propionate.
In a small study in healthy volunteers, the slightly less potent CYP3A inhibitor ketoconazole increased the exposure of fluticasone propionate after a single inhalation by 150%. This resulted in a greater reduction of plasma cortisol as compared with fluticasone propionate alone. Co-treatment with other potent CYP3A inhibitors, such as itraconazole, is also expected to increase the systemic fluticasone propionate exposure and the risk of systemic side-effects. Caution is recommended and long-term treatment with such drugs should, if possible, be avoided.
There are no data on human fertility. Animal studies indicates no effects of fluticasone propionate on male or female fertility.
There are limited data in pregnant women. Administration of fluticasone propionate during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the fetus. It is important, that the dose of inhaled corticosteroid is titrated to the lowest dose at which effective control is maintained. Treatment with fluticasone propionate should not be stopped abruptly.
Results from a retrospective epidemiological study did not find an increased risk of major congenital malformations following exposure to fluticasone propionate when compared to other inhaled corticosteroids, during the first trimester of pregnancy (see section 5.1).
Reproductive studies in animals have shown only those effects characteristic of glucocorticosteroids at systemic exposures in excess of those seen at the recommended inhaled therapeutic dose. There is inadequate evidence of safety of fluticasone propionate in human pregnancy. Data on a limited number (200) of exposed pregnancies indicate no adverse effects of fluticasone propionate on pregnancy or the health of the foetus/new born child. To date no other relevant epidemological data are available. Administration of corticosteroids to pregnant animals can cause abnormalities of fetal development, including cleft palate and intra-uterine growth retardation. There may therefore be a very small risk of such effects in the human fetus. It should be noted, however, that the fetal changes in animals occur after relatively high systemic exposure. Because fluticasone propionate delivers fluticasone propionate directly to the lungs by the inhaled route it avoids the high level of exposure that occurs when corticosteroids are given by systemic routes. Administration of fluticasone propionate during pregnancy should only be considered if the expected benefit to the mother is greater than any possible risk to the fetus (see section 5.3).
The excretion of fluticasone propionate into human breast milk has not been investigated. When measurable plasma levels were obtained in lactating laboratory rats following subcutaneous administration there was evidence of fluticasone propionate in the breast milk. However, plasma levels in patients following inhaled application of fluticasone propionate at recommended doses are likely to be low. A risk to the newborns/infants cannot be excluded.
Administration during lactation should only be considered if the expected benefit to the mother is greater than any possible risk to the child.
Fluticasone propionate has no or negligible influence on the ability to drive and use machines.
Adverse events are listed below by system organ class and frequency. Frequencies are defined as: very common (>1/10), common (>1/100 to <1/10), uncommon (>1/1000 to <1/100), rare (>1/10,000 to <1/1000) and very rare (<1/10,000) including isolated reports and not known (cannot be estimated from the available data). Very common, common and uncommon events were generally determined from clinical trial data. Rare and very rare events were generally determined from spontaneous data.
Very common: Candidiasis of mouth and throat.
Candidiasis (thrush) of the mouth and throat occurs in some patients. Such patients may find it helpful to rinse out their mouth with water after using their medication. Symptomatic candidiasis can be treated with topical anti-fungal therapy whilst still continuing with the fluticasone propionate.
Common: Pneumonia (in COPD patients).
Rare: Oesophageal candidiasis
Hyper sensitivity reactions with the following manifestations have been reported:
Uncommon: Cutaneous hyper sensitivity reactions.
Very rare: Angioedema (mainly facial and oropharyngeal oedema), respiratory symptoms (dyspnoea and/or bronchospasm) and anaphylactic reactions.
Possible systemic effects (see section 4.4) include:
Very rare: Cushing’s syndrome, Cushingoid features (such as adrenal suppression, growth retardation, decreased bone mineral density, cataract, glaucoma).
Very rare: Hyperglycaemia.
Very rare: Anxiety, sleep disorders and behavioural changes, including hyperactivity and irritability (predominantly in children).
Not known: Depression, aggression(predominantly in children)
Not known: vision, blurred (see section 4.4)
Common: Hoarseness/Dysphonia.
Not known: Epistaxis
In some patients inhaled fluticasone propionate may cause hoarseness. It maybe helpful to rinse out the mouth with water immediately after inhalation.
Very rare: Paradoxical bronchospasm.
As with other inhalation therapy, paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing. This should be treated immediately with a fast-acting inhaled bronchodilator. Fluticasone propionate should be discontinued immediately, the patient assessed, and if necessary alternative therapy instituted.
Very rare: Dyspepsia
Common: Contusions
Very rare: Arthralgia
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 HPRA Pharmacovigilance, Earlsfort Terrace, IRL – Dublin 2; Tel: +353 1 6764971; Fax: +353 1 6762517. Website: www.hpra.ie; E-mail: medsafety@hpra.ie.
Not applicable.
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