Flixotide Evohaler 125mcg

Update to section 4.4 – addition of Visual Disturbance section (blurred vision)

Update to section 4.8 – addition of Eye Disorders section (blurred vision)

Update section 4.5 of SmPC to align to PRAC recommendation on drug interactions.

Section 4.4 Special Warnings and Precautions for Use

Information relevant to Pneumonia in patients with COPD



Section 4.6 - Updated information on pregnancy and lactation

Section 5.1 - Updated information on pregnancy and lactation

Change to address of the Irish MA Holder

Section 4.8 updated to include

Epistaxis in frequency table as not known

 

Section 7 – Removal of A&H trading style

Section 4.8 – Inclusion of adverse reaction

Section 4.8 - adverse event reporting - updated details from IMB to HPRA

Changes to:

Section 4.2 - Posology and method of administration
Section 4.4 - Special warnings and precautions for use,
Section 4.8 - Undesirable effects,
Section 6.4 - Special precautions for storage,
Section 7 - MARKETING AUTHORISATION HOLDER,

4.4 Special Warnings and Precautions for Use

The following paragraph was updated to specify the warning for asthma:

Flixotide Diskus 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.

 

Added Possible systemic effects Cushing’s syndrome, Cushingoid features

 

Added the following wording as required following the PhVWP decision:

Possible systemic effects include… a range of psychological or behavioural effects including psychomotor hyperactivity, sleep disorders, anxiety, depression or aggression (particularly in children).

 

Replaced the previous warnings regarding adrenal suppression, adrenal crisis and impaired adrenal reserve with the following:

The possibility of impaired adrenal response should always be borne in mind in emergency situations, including surgery, and elective situations likely to produce stress and appropriate corticosteroid treatment must be considered (see section 4.9).

 

Adrenal function and adrenal reserve usually remain within the normal range on recommended doses of fluticasone propionate 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.

 

Deleted the following warning regarding use of topical corticosteroids:

Particular care should be taken to minimise use of topical corticosteroids in patients with immunosuppression.

 

Replaced the warning on co-administration with Ritonavir to read:

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 outweighs the risk of systemic corticosteroid side-effects (see section 4.5).

 

Added the following warning regarding diabetes mellitus:

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.

 

4.5 Interaction with Other Medicinal Products and Other Forms of Interaction

Replaced the interaction warning regarding ritonavir with the following:

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.  During post-marketing use, there have been reports of clinically significant drug interactions in patients receiving intranasal or inhaled 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 outweighs the risk of systemic corticosteroid side-effects.

 

Replaced the warning regarding co-administration with CYP3A inhibitors with a warning regarding other inhibitors of cytochrome P450 3A4, as follows

Studies have shown that other inhibitors of cytochrome 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 cytochrome P450 3A4 inhibitors (e.g. ketoconazole) as there is potential for increased systemic exposure to fluticasone propionate.

 

4.6 Pregnancy and Lactation

Replaced the entire text of this section with the following text under the new subheadings ‘Pregnancy’ and ‘Lactation’:

Pregnancy

There is inadequate evidence of safety of fluticasone propionate in human pregnancy.  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.  Tests for genotoxicity have shown no mutagenic potential.

 

However, as with other drugs the 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 foetus.

 

Lactation

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.

 

 

4.8 Undesirable Effects

 

Infections and Infestations

Updated the instructions on how to mitigate the effects of candidiasis of the mouth and throat (thrush) to read:

Such patients may find it helpful to rinse out their mouth with water after using their medication

 

Endocrine Disorders

Added very rare undesirable effects Cushing’s syndrome and Cushingoid features

 

Added the following undesirable effects:

Metabolism and nutrition disorders

Very rare: Hyperglycaemia.

 

Psychiatric disorders

Very rare: Anxiety, sleep disorders and behavioural changes, including hyperactivity and irritability (predominantly in children).

Frequency not known: Depression, aggression (predominantly in children)

 

Respiratory, Thoracic and Mediastinal Disorders

Updated the instructions on how to mitigate the effects of hoarseness to read:

In some patients inhaled fluticasone propionate may cause hoarseness.  It may be helpful to rinse out the mouth with water immediately after inhalation.

 

Updated the statement ‘As with other inhalation therapy, paradoxical bronchospasm may occur’ with the following additional statements:

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.

 

4.9 Overdose

Updated to include two subsections ‘Signs and symptoms’ and ‘Treatment’

Symptoms and Signs

Acute inhalation of fluticasone propionate doses in excess of those approved may lead to temporary suppression of the hypothalamic-pituitary-adrenal axis.  This does not usually require emergency action, as normal adrenal function typically recovers within a few days.

 

If higher than approved doses are continued over prolonged periods, significant adrenocortical suppression is possible.  There have been very rare reports of acute adrenal crisis occurring in children exposed to higher than approved doses (typically 1000 micrograms daily and above), over prolonged periods (several months or years); observed features included hypoglycaemia and sequelae of decreased consciousness and/or convulsions.  Situations which could potentially trigger acute adrenal crisis include exposure to trauma, surgery, infection or any rapid reduction in dosage.

 

Treatment

Patients receiving higher than approved doses should be managed closely and the dose reduced gradually.