Relvar Ellipta

/ GSK

Asthma
Patients with asthma should be given the strength of Relvar Ellipta containing the appropriate fluticasone furoate (FF) dosage for the severity of their disease. Prescribers should be aware that in patients with asthma, fluticasone furoate (FF) 100 micrograms once daily is approximately equivalent to fluticasone propionate (FP) 250 micrograms twice daily, while FF 200 micrograms once daily is approximately equivalent to FP 500 micrograms twice daily.
Adults and adolescents aged 12 years and over: A starting dose of one inhalation of Relvar Ellipta 92/22 micrograms once daily should be considered for adults and adolescents 12 years and over who require a low to mid dose of inhaled corticosteroid in combination with a long-acting beta2-agonist. If patients are inadequately controlled on Relvar Ellipta 92/22 micrograms, the dose can be increased to 184/22 micrograms, which may provide additional
improvement in asthma control.
Patients should be regularly reassessed by a healthcare professional so that the strength of fluticasone furoate/vilanterol they are receiving remains optimal and is only changed on medical advice. The dose should be titrated to the lowest dose at which effective control of symptoms is maintained.
Relvar Ellipta 184/22 micrograms should be considered for adults and adolescents 12 years and over who require a higher dose of inhaled corticosteroid in combination with a long-acting beta2-agonist.
Patients usually experience an improvement in lung function within 15 minutes of inhaling Relvar Ellipta.
However, the patient should be informed that regular daily usage is necessary to maintain control of asthma symptoms and that use should be continued even when asymptomatic.
If symptoms arise in the period between doses, an inhaled, short-acting beta2-agonist should be used for immediate relief.
The maximum recommended dose is Relvar Ellipta 184/22 micrograms once daily.
Children aged under 12 years: The safety and efficacy of This product in children under 12 years of age has not yet been established in the indication for asthma. No data are available.
COPD
Adults aged 18 years and over: One inhalation of the formulation of 92/22 micrograms once daily. The formulation of 184/22 micrograms is not indicated for patients with COPD. There is no additional benefit of the 184/22 micrograms dose compared to the 92/22 micrograms dose and there is a potential increased risk of pneumonia and systemic corticosteroid-related adverse reactions. Patients usually experience an improvement in lung function within 16-17 minutes of inhaling this product.
Paediatric population: There is no relevant use of this product in the paediatric population in the indication for COPD.
Elderly patients (>65 years): No dose adjustment is required in this population.
Renal impairment: No dose adjustment is required in this population.
Hepatic impairment: Studies in subjects with mild, moderate and severe hepatic impairment showed an increase in systemic exposure to fluticasone furoate (both Cmax and AUC). Caution should be exercised when dosing patients with hepatic impairment who may be more at risk of systemic adverse reactions associated with corticosteroids. For patients with moderate or severe hepatic impairment the maximum dose is 92/22 micrograms.
Method of administration: Relvar Ellipta is for inhalation use only.
It should be administered at the same time of the day, each day.
The final decision on evening or morning dosing should be left to the discretion of the physician.
If a dose is missed the next dose should be taken at the usual time the next day.
If stored in a refrigerator, the inhaler should be allowed to return to room temperature for at least an hour before use.

Asthma: Relvar Ellipta 92/22 mcg and Relvar Ellipta 184/22 mcg is indicated for the regular treatment of asthma in adults and adolescents aged 12 years and older where use of a combination medicinal product (long-acting beta2-agonist and inhaled corticosteroid) is appropriate:
• patients not adequately controlled with inhaled corticosteroids and ‘as needed’ inhaled short acting beta2-agonists.
• patients already adequately controlled on both inhaled corticosteroid and long-acting beta2-agonist.
COPD (Chronic Obstructive Pulmonary Disease): Relvar Ellipta 92/22 mcg is indicated for the symptomatic treatment of adults with COPD with a FEV1<70%
predicted normal (post-bronchodilator) with an exacerbation history despite regular bronchodilator therapy.

Hypersensitivity to the active substance or to any of the excipients.

Deterioration of disease: Fluticasone furoate/vilanterol should not be used to treat acute asthma symptoms or an acute exacerbation in COPD, for which a short-acting bronchodilator is required. Increasing use of short-acting bronchodilators to relieve symptoms indicates deterioration of control and patients should be reviewed by a physician. Patients should not stop therapy with fluticasone furoate/vilanterol in asthma or COPD, without physician supervision since symptoms may recur after discontinuation. Asthma-related adverse events and exacerbations may occur during treatment with fluticasone furoate/vilanterol. Patients should be asked to continue treatment but to seek medical advice if asthma symptoms remain uncontrolled or worsen after initiation of treatment with this product.
Paradoxical bronchospasm: Paradoxical bronchospasm may occur with an immediate increase in wheezing after dosing. This should be treated immediately with a short-acting inhaled bronchodilator. This product should be discontinued immediately, the patient assessed and alternative therapy instituted if necessary.
Cardiovascular effects: Cardiovascular effects, such as cardiac arrhythmias e.g. supraventricular tachycardia and extrasystoles may be seen with sympathomimetic medicinal products including This product. Therefore fluticasone furoate/vilanterol should be used with caution in patients with severe cardiovascular disease or heart rhythm abnormalities, thyrotoxicosis, uncorrected hypokalaemia or patients predisposed to low levels of serum potassium.
Patients with hepatic impairment: For patients with moderate to severe hepatic impairment, the 92/22 micrograms dose should be used and patients should be monitored for systemic corticosteroid-related adverse reactions.
Systemic corticosteroid effects: 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. Possible systemic effects include Cushing’s syndrome, Cushingoid features, adrenal suppression, decrease in bone mineral density, growth retardation in children and adolescents, 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). Fluticasone furoate/vilanterol should be administered with caution in patients with pulmonary tuberculosis or in patients with chronic or untreated infections.
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.
Hyperglycaemia: There have been reports of increases in blood glucose levels in diabetic patients and this should be considered when prescribing to patients with a history of diabetes mellitus.
Pneumonia in patients with COPD: 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.
Pneumonia in patients with asthma: The incidence of pneumonia in patients with asthma was common at the higher dose. The incidence of pneumonia in patients with asthma taking fluticasone furoate/vilanterol 184/22 micrograms was numerically higher compared with those receiving fluticasone furoate/vilanterol 92/22 micrograms or placebo. No risk factors were identified.
Excipients: Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicinal product.

The most commonly reported adverse reactions with fluticasone furoate and vilanterol were headache and nasopharyngitis. With the exception of pneumonia and fractures, the safety profile was similar in patients with asthma and COPD. During clinical studies, pneumonia and fractures were more frequently commonly observed in patients with COPD.
Other common adverse events: Upper respiratory tract infection, bronchitis, Influenza, candidiasis of mouth and throat, extrasystoles, oropharyngeal pain, sinusitis, pharyngitis, rhinitis, cough, dysphonia, abdominal pain, arthralgia, back pain, pyrexia.
See prescribing information for full details.

Interaction with beta-blockers: Beta2-adrenergic blockers may weaken or antagonise the effect of beta2-adrenergic agonists. Concurrent use of both non-selective and selective beta2-adrenergic blockers should be avoided unless there are compelling reasons for their use.
Interaction with CYP3A4 inhibitors: Fluticasone furoate and vilanterol are both rapidly cleared by extensive first pass metabolism mediated by the liver enzyme CYP3A4. Caution is advised when co-administering with strong CYP 3A4 inhibitors (e.g. ketoconazole, ritonavir) as there is potential for increased systemic exposure to both fluticasone furoate and vilanterol, and concomitant use should be avoided. A repeat dose CYP3A4 drug interaction study was performed in healthy subjects with the fluticasone furoate/vilanterol combination (184/22 micrograms) and the strong CYP3A4 inhibitor ketoconazole (400mg). Co-administration increased mean fluticasone furoate AUC(0-24) and Cmax by 36% and 33%, respectively. The increase in fluticasone furoate exposure was associated with a 27% reduction in 0-24 hours weighted mean serum cortisol. Co-administration increased mean vilanterol AUC(0-t) and Cmax 65% and 22%, respectively. The increase in vilanterol exposure was not associated with an increase in beta2-agonist related systemic effects on heart rate, blood potassium or QTcF interval.
Interaction with P-glycoprotein inhibitors: Fluticasone furoate and vilanterol are both substrates of P-glycoprotein (P-gp). A clinical pharmacology study in healthy subjects with co-administered vilanterol and the potent P-gp and moderate CYP3A4 inhibitor verapamil did not show any significant effect on the pharmacokinetics of vilanterol. Clinical pharmacology studies with a specific P-gp inhibitor and fluticasone furoate have not been conducted.
Sympathomimetic medicinal products: Concomitant administration of other sympathomimetic medicinal products (alone or as part of combination therapy) may potentiate the adverse reactions of fluticasone furoate/vilanterol. This product should not be used in conjunction with other long-acting beta2-adrenergic agonists or medicinal products containing long-acting beta2-adrenergic agonists.
Paediatric population: Interaction studies have only been performed in adults.

Pregnancy: There are no or limited data from the use of fluticasone furoate and vilanterol trifenatate in pregnant women. Administration of fluticasone furoate/vilanterol to pregnant women should only be considered if the expected benefit to the mother is greater than any possible risk to the foetus.
Lactation: There is insufficient information on the excretion of fluticasone furoate or vilanterol trifenatate and/or metabolites in human milk. However, other corticosteroids and beta2-agonists are detected in human milk. A risk to breastfed newborns/infants cannot be excluded. A decision must be made whether to discontinue breast-feeding or to discontinue fluticasone furoate/vilanterol therapy taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman.          

Symptoms and signs: An overdose of fluticasone furoate/vilanterol may produce signs and symptoms due to the individual component’s actions, including those seen with overdose of other beta2-agonists and consistent with the known inhaled corticosteroid class effects.
Treatment: There is no specific treatment for an overdose with fluticasone furoate/vilanterol. If overdose occurs, the patient should be treated supportively with appropriate monitoring as necessary. Cardioselective beta-blockade should only be considered for profound vilanterol overdose effects that are clinically concerning and unresponsive to supportive measures. Cardioselective beta-blocking medicinal products should be used with caution in patients with a history of bronchospasm. Further management should be as clinically indicated or as recommended by the national poisons centre,
where available.

Lactose: Each delivered dose contains approximately 25 mg of lactose (as monohydrate).
Storage: If stored in a refrigerator, the inhaler should be allowed to return to room temperature for at least an hour before use. Store in the original package in order to protect from moisture.
Shelf-life: To be used within 6 weeks of first opening of the tray.