Only changes have been made to the alternative batch release site. No change to the actual manufacturer/batch release site

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

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

Epistaxis in frequency table as not known

Section 4.8 – Inclusion of adverse reaction

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

Section 4.4 - Special warnings and precautions for use,
Section 4.8 - Undesirable effects,
Section 7 - MARKETING AUTHORISATION HOLDER

4.2 Posology and Method of Administration

The following instruction/warning was added:

Fluticasone propionate for nebulisation should not be injected.

The instruction regarding the prophylactic nature of fluticasone propionate was updated to highlight that it should be taken regularly, even when the patient is asymptomatic.

4.4 Special Warnings and Special Precautions for Use

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

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.

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:

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.  The possibility of impaired adrenal response should always be borne in mind in emergency situations, including surgery, which are likely to produce stress and appropriate corticosteroid treatment must be considered.

Added the warning:

Treatment with fluticasone propionate should not be stopped abruptly.

Added the following warning regarding diabetes mellitus:

There have been very rare reports of increases in blood glucose levels (see 4.8 Undesirable Effects) and this should be considered when prescribing to patients with a history of diabetes mellitus.

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 4.5 Interaction with Other Medicinal Products and Other Forms of Interaction).

4.5 Interaction with Other Medicaments 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

Added the subheadings ‘Pregnancy’ and ‘Lactation’

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 recommended may lead to temporary suppression of adrenal function.  This does not need emergency action as adrenal function is recovered in a few days, as verified by plasma cortisol measurements.  However if higher than recommended dosage is continued over prolonged periods, some degree of adrenal suppression may result.  Monitoring of adrenal reserve may be necessary.  In cases of fluticasone propionate overdose, therapy may still be continued at a suitable dosage for symptom control.

Treatment

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