GSK’s continued commitment to innovative respiratory research demonstrated in European Respiratory Society congress data presentations

GlaxoSmithKline plc (GSK) will provide updates on emerging areas of research with data from across its comprehensive respiratory portfolio of approved medicines, investigational programmes and scientific collaborations, at the European Respiratory Society (ERS) International Congress, 3rd -7th  September, London, UK. More than 30 abstracts from the company will be featured at the meeting.                                                                              

Highlights include data from a number of key studies:

  • FULFIL, the pivotal phase III study for the investigational once-daily ‘closed’ triple combination therapy, fluticasone furoate/umeclidinium/vilanterol (FF/UMEC/VI 100/62.5/25mcg), a combination inhaled corticosteroid, long-acting muscarinic antagonist, long-acting beta2 agonist, compared to the inhaled corticosteroid and single bronchodilator treatment, budesonide/formoterol (400/12mcg) delivered in the Turbohaler® inhaler in patients with chronic obstructive pulmonary disease (COPD). Results will report on the co-primary endpoints of lung function and health-related quality of life as measured by SGRQ, as well as a secondary endpoint assessing annual rate of moderate/severe exacerbations and safety data over 24 weeks and 52 weeks of treatment. Headline data from the study were announced in June, and regulatory submissions for the closed triple therapy in the US and Europe are anticipated by end of 2016.
  • The Salford Lung Study in COPD, an innovative randomised controlled trial, designed to measure the effectiveness and safety of Relvar® Ellipta® (fluticasone furoate/vilanterol or FF/VI 100/25mcg)  when compared with patients’ usual care for COPD and undertaken in an everyday clinical practice setting. Results will report on the primary endpoint of annual rate of moderate/severe exacerbations and safety findings.
  • Vestri, GSK’s long-term safety study for Advair® Diskus® (fluticasone propionate/salmeterol) comparedto fluticasone propionate monotherapy, to treat children aged 4-11 years with asthma. This was undertaken by GSK as a post-marketing requirement of the US Food and Drug Administration (FDA). Results will report on the primary safety endpoint and primary efficacy data. 

Data will also be presented which provide insight into the burden of severe asthma and characterize the role of GSK’s anti-IL 5 monoclonal antibody, Nucala® (mepolizumab), in the treatment of patients with severe refractory eosinophilic asthma. Exploratory data for GSK’s dual bronchodilator treatment for COPD, Anoro® Ellipta® (umeclidinium/vilanterol, UMEC/VI), investigates the risk of experiencing clinically important deteriorations in COPD, following an escalation of treatment from single bronchodilator tiotropium to UMEC/VI.

Professor Neil Barnes, Global Franchise Medical Head, Respiratory said: “We are delighted that this year’s ERS is taking place in our home city of London. As the largest respiratory scientific meeting in the world, the ERS provides a great forum to share and debate the ongoing research we are conducting to advance respiratory science and help patients with lung disease. Our approach to research starts with our understanding that each patient is different. That is why our discovery and development work is focused on understanding patient types and our clinical programmes on generating evidence that supports a clinician’s ability to select the right medicine for the right patients. This has resulted in GSK’s broad portfolio of respiratory medicines, with a treatment option available at each stage of disease as defined in international guidelines for asthma and COPD.”

Commitment to respiratory disease

GSK has been a leader in respiratory for over 45 years, developing new and first-in-class medicines, approaches and insights, which have helped to influence and support the management of asthma and COPD.       The company is constantly striving to expand knowledge and the understanding of respiratory disease to help transform the way that medicines are developed and is focused on identifying new scientific insights, applying our expertise and developing innovative new medicines that enable clinicians to tailor treatment to patients’ individual needs.

About COPD

COPD is a disease of the lungs that includes chronic bronchitis, emphysema or both. COPD is characterised by obstruction to airflow that interferes with normal breathing.COPD is thought to affect 329 million people worldwide.

Long-term exposure to lung irritants that damage the lungs and the airways are usually the cause of COPD. Cigarette smoke, breathing in second hand smoke, air pollution, chemical fumes or dust from the environment or workplace can all contribute to COPD. Most people who have COPD are at least 40 years old when symptoms begin.

About asthma and severe asthma

Current estimates indicate that as many as 242 million people live with asthma worldwide. For many of these patients, existing therapies can provide adequate control of their symptoms if used appropriately. However, up to 5% of patients with asthma have difficulty in achieving symptom control with existing therapies. Severe asthma is defined as asthma which requires treatment with high dose inhaled corticosteroids (ICS) plus a second controller (and/or systemic corticosteroids) to prevent it from becoming ‘uncontrolled’ or which remains ‘uncontrolled’ despite this therapy. Severe asthma patients are also often categorised by long-term use of oral corticosteroids (OCS).

About Relvar®/Breo® Ellipta® (fluticasone furoate/vilanterol or FF/VI)

Breo® Ellipta® 100/25mcg (FF/VI) is licensed in the US for:

  • the long-term, once-daily, maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema and to reduce exacerbations of COPD in patients with a history of exacerbations. BreoEllipta 100/25mcg is the only strength indicated for the treatment of COPD.
  • Breo Ellipta100/25mcg is not indicated for the relief of acute bronchospasm.

Full US prescribing information, including BOXED WARNING and Medication Guide is available at us.gsk.com or US Prescribing Information Breo Ellipta.                                                      

Relvar Ellipta(FF/VI) is approved in Europe for:

  • the symptomatic treatment of adults with chronic obstructive pulmonary disease (COPD) with a FEV1<70% predicted normal (post-bronchodilator) with an exacerbation history despite regular bronchodilator therapy.

For the EU Summary of Product Characteristics for Relvar Ellipta, please visit: http://ec.europa.eu/health/documents/community-register/html/h886.htm 

Important Safety Information for Breo Ellipta

The following ISI is based on the Highlights section of the US Prescribing Information for Breo Ellipta. Please consult the full Prescribing Information for all the labelled safety information for Breo Ellipta. 

Long-acting beta2-adrenergic agonists (LABA), such as vilanterol, one of the active ingredients in BREO ELLIPTA, increase the risk of asthma-related death. A placebo-controlled trial with another LABA (salmeterol) showed an increase in asthma-related deaths. This finding with salmeterol is considered a class effect of all LABA. Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids (ICS) or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA.

Breo Ellipta is contraindicated for primary treatment of status asthmaticus or other acute episodes of COPD or asthma where intensive measures are required and in patients with severe hypersensitivity to milk proteins or who have demonstrated hypersensitivity to either fluticasone furoate, vilanterol, or any of the excipients.

Breo Ellipta should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD or asthma, or used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. Acute symptoms should be treated with an inhaled, short-acting beta2-agonist.

Breo Ellipta should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medications containing LABAs, as an overdose may result.

Oropharyngeal candidiasis has occurred in patients treated with Breo Ellipta. Patients should be advised to rinse their mouth with water without swallowing after inhalation to help reduce this risk.

An increase in the incidence of pneumonia has been observed in subjects with COPD receiving the fluticasone furoate/vilanterol combination, including Breo Ellipta 100 mcg/25 mcg, in clinical trials. There was also an increased incidence of pneumonias resulting in hospitalisation. In some incidences these pneumonia events were fatal.

Patients who use corticosteroids are at risk for potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. A more serious or even fatal course of chickenpox or measles may occur in susceptible patients.

Particular care is needed for patients who have been transferred from systemically active corticosteroids to inhaled corticosteroids because deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids.

Hypercorticism and adrenal suppression may occur with very high dosages or at the regular dosage of inhaled corticosteroids in susceptible individuals. 

Caution should be exercised when considering the coadministration of Breo Ellipta with long‐term ketoconazole and other known strong CYP3A4 inhibitors because increased systemic corticosteroid and cardiovascular adverse effects may occur. 

Breo Ellipta can produce paradoxical bronchospasm which may be life-threatening.

Hypersensitivity reactions such as anaphylaxis, angioedema, rash, and urticaria may occur after administration of Breo Ellipta.

Vilanterol, the LABA in Breo Ellipta, can produce clinically significant cardiovascular effects in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, and also cardiac arrhythmias. Breo Ellipta should be used with caution in patients with cardiovascular disorders.

Decreases in bone mineral density have been observed with long-term administration of products containing inhaled corticosteroids, as have glaucoma, increased intraocular pressure, and cataracts.

Breo Ellipta should be used with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines. 

Beta-adrenergic agonist medicines may produce significant hypokalemia in some patients.  Beta-adrenergic agonist medicines may produce transient hyperglycemia in some patients.

For COPD, the most common adverse reactions (≥3% and more common than in placebo) reported in two 6-month clinical trials with Breo Ellipta 100/25 (and placebo) were nasopharyngitis, 9% (8%); upper respiratory tract infection, 7% (3%); headache, 7% (5%); and oral candidiasis, 5% (2%).  In addition to the reactions reported in the 6-month studies, adverse reactions occurring in ≥3% of the subjects treated with Breo Ellipta 100/25 in two 1-year studies included back pain, pneumonia, bronchitis, sinusitis, cough, oropharyngeal pain, arthralgia, influenza, pharyngitis, and pyrexia.

About Anoro® Ellipta®  (umeclidinium/vilanterol, UMEC/VI)

Anoro Ellipta is a combination long-acting muscarinic antagonist (LAMA) (also known as an anticholinergic) / long-acting beta2-adrenergic agonist (LABA).

In the US, Anoro Ellipta is indicated for the long-term, once-daily, maintenance treatment of airflow obstruction in patients with COPD, including chronic bronchitis and/or emphysema. Anoro Ellipta is not indicated for the relief of acute bronchospasm or for the treatment of asthma. The FDA-approved strength is umeclidinium/vilanterol 62.5/25mcg. Full US prescribing information, including BOXED WARNING and Medication Guide are available at: https://www.gsksource.com/gskprm/htdocs/documents/ANORO-ELLIPTA-PI-MG.PDF.

In Europe, Anoro is indicated as a once-daily, maintenance bronchodilator treatment to relieve symptoms in adult patients with COPD. The approved strength in Europe is UMEC/VI 55mcg/22mcg (delivered dose, equivalent to 62.5mcg/25mcg pre-dispensed dose). For the EU Summary of Product Characteristics (SmPC), please visit: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002751/WC500168424.pdf  

Important Safety Information for Anoro Ellipta

The following Important Safety Information is based on the Highlights section of the Prescribing Information for Anoro Ellipta. Please consult the full Prescribing Information for all the labelled safety information for Anoro Ellipta.

Long-acting beta2-adrenergic agonists (LABAs), such as vilanterol, one of the active ingredients in Anoro Ellipta, increase the risk of asthma-related death. A placebo-controlled trial with another LABA (salmeterol) showed an increase in asthma-related deaths in subjects receiving salmeterol. This finding with salmeterol is considered a class effect of all LABAs, including vilanterol. The safety and efficacy of Anoro Ellipta in patients with asthma have not been established. Anoro Ellipta is not indicated for the treatment of asthma. 

Anoro Ellipta is contraindicated in patients with severe hypersensitivity to milk proteins or who have demonstrated hypersensitivity to either umeclidinium, vilanterol, or any of the other ingredients.

Anoro Ellipta should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD, or as rescue therapy for the treatment of acute episodes of bronchospasm, which should be treated with an inhaled, short-acting beta2-agonist.

Anoro Ellipta should not be used more often than recommended, at higher doses than recommended, or in conjunction with additional medicine containing a LABA, as an overdose may result.

Anoro Ellipta should be used with caution when considering coadministration with long-term ketoconazole and other known strong cytochrome P450 3A4 inhibitors because increased cardiovascular adverse effects may occur.

As with other inhaled medicines, Anoro Ellipta can produce paradoxical bronchospasm, which may be life-threatening.

Hypersensitivity reactions such as anaphylaxis, angioedema, rash, and urticaria may occur after administration of Anoro Ellipta. Discontinue Anoro Ellipta if such reactions occur. 

Anoro Ellipta should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

Anoro Ellipta should be used with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines.

Anoro Ellipta should be used with caution in patients with narrow-angle glaucoma. Instruct patients to contact a physician immediately should any signs or symptoms of narrow-angle glaucoma occur.

Anoro Ellipta should be used with caution in patients with urinary retention, especially in patients with prostatic hyperplasia or bladder neck obstruction. Instruct patients to contact a physician immediately should any signs or symptoms of urinary retention occur.

Beta-adrenergic agonist medicines may produce significant hypokalemia and transient hyperglycemia in some patients.

The most common adverse reactions (incidence ≥1% and more common than placebo) reported in four 6-month clinical trials with Anoro Ellipta (and placebo) were pharyngitis, 2% (<1%); sinusitis 1% (<1%); lower respiratory tract infection, 1% (<1%); constipation, 1% (<1%); diarrhea, 2% (1%); pain in extremity 2% (1%); muscle spasms, 1% (<1%); neck pain, 1% (<1%); and chest pain 1% (<1%). In addition to the 6-month efficacy trials with Anoro Ellipta, a 12-month trial evaluated the safety of umeclidinium/vilanterol 125 mcg/25 mcg in subjects with COPD. Adverse reactions (incidence ≥1% and more common than placebo) in subjects receiving umeclidinium/vilanterol 125 mcg/25 mcg were: headache, back pain, sinusitis, cough, urinary tract infection, arthralgia, nausea, vertigo, abdominal pain, pleuritic pain, viral respiratory tract infection, toothache, and diabetes mellitus.

Beta2-agonists, such as vilanterol should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors, tricyclic antidepressants, or drugs known to prolong the QTc interval or within 2 weeks of discontinuation of such agents, because the effect of adrenergic agonists on the cardiovascular system may be potentiated.

Use beta blockers with caution as they not only block the pulmonary effect of beta2-agonists, such as vilanterol, but may produce severe bronchospasm in patients with COPD.

Use with caution in patients taking non–potassium-sparing diuretics, as electrocardiographic changes and/or hypokalemia associated with non–potassium-sparing diuretics may worsen with concomitant beta-agonists.

Avoid co-administration of Anoro Ellipta with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects such as cardiovascular effects, worsening of narrow-angle glaucoma, and worsening of urinary retention.

About Nucala® (mepolizumab)

Nucala is a monoclonal antibody that binds to IL-5, preventing it from binding to its receptor on the surface of eosinophils. Inhibiting IL-5 binding in this way reduces blood, tissue and sputum eosinophil levels.

In the US Nucala is licensed as an add-on maintenance treatment for patients with severe asthma aged 12 years and older, and with an eosinophilic phenotype. Nucala is not approved for the treatment of other eosinophilic conditions or relief of acute bronchospasm or status asthmaticus. Full US Prescribing Information is available at US Prescribing Information Nucala.

In the EU Nucala is licensed as an add-on treatment for severe refractory eosinophilic asthma in adult patients. For the EU Summary of Product Characteristics for Nucala, please visit: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/003860/WC500198037.pdf

Nucala has also been approved in Canada, Australia, Japan, Switzerland and South Korea. Further regulatory applications have been submitted and are under review in other countries.

Important safety information for Nucala

The following information is based on the Highlights section of the US Prescribing Information for Nucala.  Please consult the full Prescribing Information for all the labelled safety information for Nucala.

CONTRAINDICATIONS

Nucala should not be administered to patients with a history of hypersensitivity to mepolizumab or excipients in the formulation.

WARNINGS AND PRECAUTIONS

Hypersensitivity Reactions

Hypersensitivity reactions (eg, angioedema, bronchospasm, hypotension, urticaria, rash) have occurred following administration of Nucala. These reactions generally occur within hours of administration but in some instances can have a delayed onset (i.e. days). In the event of a hypersensitivity reaction, Nucala should be discontinued.

Acute Asthma Symptoms or Deteriorating Disease                                                 

Nucala should not be used to treat acute asthma symptoms, acute exacerbations, or acute bronchospasm.

Opportunistic Infections: Herpes Zoster

In controlled clinical trials, 2 serious adverse reactions of herpes zoster occurred in subjects treated with Nucala compared to none in placebo. Consider varicella vaccination if medically appropriate prior to starting therapy with Nucala.

Reduction of Corticosteroid Dosage

Do not discontinue systemic or inhaled corticosteroids (ICS) abruptly upon initiation of therapy with Nucala. Decreases in corticosteroid doses, if appropriate, should be gradual and under the direct supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

Parasitic (Helminth) Infection

It is unknown if Nucala will influence a patient’s response against parasites. Treat patients with pre-existing helminth infections before initiating therapy with Nucala. If patients become infected while receiving treatment with Nucala and do not respond to anti-helminth treatment, discontinue treatment with Nucala until infection resolves.

ADVERSE REACTIONS

The most common adverse reactions (≥3% and more common than placebo) reported in the first 24 weeks of 2 clinical trials with Nucala (and placebo) were: headache, 19% (18%); injection site reaction, 8% (3%); back pain, 5% (4%); fatigue, 5% (4%); influenza, 3% (2%); urinary tract infection 3% (2%); abdominal pain upper, 3% (2%); pruritus, 3% (2%); eczema, 3% (<1%); and muscle spasm, 3% (<1%).

Systemic Reactions, including Hypersensitivity Reactions:  In 3 clinical trials, 10% of subjects who received Nucala experienced systemic (allergic and nonallergic) and local site reactions compared to 7% in the placebo group. Systemic allergic/hypersensitivity reactions were reported by 1% of subjects who received Nucala compared to 2% of subjects in the placebo group. Manifestations included rash, pruritus, headache, and myalgia. Systemic nonallergic reactions were reported by 2% of subjects who received Nucala and 3% of subjects in the placebo group. Manifestations included rash, flushing, and myalgia. A majority of the systemic reactions were experienced on the day of dosing.

Injection Site Reactions: Injection site reactions (e.g. pain, erythema, swelling, itching, and burning sensation) occurred at a rate of 8% in subjects treated with Nucala compared with 3% in subjects treated with placebo.

USE IN SPECIFIC POPULATIONS

A pregnancy exposure registry monitors pregnancy outcomes in women exposed to Nucala during pregnancy. Healthcare providers can enrol patients or encourage patients to enrol themselves by calling 1-877-311-8972 or visiting www.mothertobaby.org/asthma.

The data on pregnancy exposures from the clinical trials are insufficient to inform on drug-associated risk. Monoclonal antibodies, such as mepolizumab, are progressively transported across the placenta in a linear fashion as pregnancy progresses; therefore, potential effects on a foetus are likely to be greater during the second and third trimesters of pregnancy.

About Advair®/Seretide® Diskus®  (salmeterol/fluticasone propionate, SFP)

ADVAIR DISKUS is indicated for the treatment of asthma in patients aged 4 years and older.

Long-acting beta2-adrenergic agonists (LABA), such as salmeterol, one of the active ingredients in ADVAIR DISKUS, increase the risk of asthma-related death. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients. Therefore, when treating patients with asthma, physicians should only prescribe ADVAIR DISKUS for patients not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid, or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and a LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g., discontinue ADVAIR DISKUS) if possible without loss of asthma control and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. Do not use ADVAIR DISKUS for patients whose asthma is adequately controlled on low- or medium-dose inhaled corticosteroids.

ADVAIR DISKUS is NOT indicated for the relief of acute bronchospasm.

https://www.gsksource.com/pharma/content/dam/GlaxoSmithKline/US/en/Prescribing_Information/Advair_Diskus/pdf/ADVAIR-DISKUS-PI-MG.PDF

Seretide Accuhaler is indicated in Europe in the regular treatment of patients aged 4 and over with asthma, where use of a combination product (long-acting ß2–agonist, LABA, and inhaled corticosteroid, ICS) is appropriate: Patients not adequately controlled on both ICS and 'as-needed' short-acting ß2-agonist (SABA); Patients already adequately controlled on both ICS and LABA.

 For the UK Summary of Product Characteristics (SmPC), please visit: https://www.medicines.org.uk/emc/medicine/2317/SPC/Seretide+100,+250,+500+Accuhaler

Important Safety Information for ADVAIR DISKUS

WARNING: ASTHMA-RELATED DEATH

Long-acting beta2-adrenergic agonists (LABA), such as salmeterol, one of the active ingredients in ADVAIR DISKUS, increase the risk of asthma-related death. Data from a large placebo-controlled US trial that compared the safety of salmeterol with placebo added to usual asthma therapy showed an increase in asthma-related deaths in subjects receiving salmeterol (13 deaths out of 13,176 subjects treated for 28 weeks on salmeterol versus 3 deaths out of 13,179 subjects on placebo). Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from LABA. Available data from controlled clinical trials suggest that LABA increase the risk of asthma-related hospitalization in pediatric and adolescent patients.

Therefore, when treating patients with asthma, physicians should only prescribe ADVAIR DISKUS for patients not adequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid, or whose disease severity clearly warrants initiation of treatment with both an inhaled corticosteroid and a LABA. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (e.g., discontinue ADVAIR DISKUS) if possible without loss of asthma control and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. Do not use ADVAIR DISKUS for patients whose asthma is adequately controlled on low- or medium-dose inhaled corticosteroids.

CONTRAINDICATIONS

  • ADVAIR DISKUS is contraindicated for primary treatment of status asthmaticus or other acute episodes of asthma or chronic obstructive pulmonary disease (COPD) where intensive measures are required.
  • ADVAIR DISKUS is contraindicated in patients with severe hypersensitivity to milk proteins.

WARNINGS AND PRECAUTIONS

  • ADVAIR DISKUS should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of asthma or COPD.
  • ADVAIR DISKUS should not be used for the relief of acute symptoms, i.e., as rescue therapy for the treatment of acute episodes of bronchospasm. An inhaled, short-acting beta2-agonist, not ADVAIR DISKUS, should be used to relieve acute symptoms such as shortness of breath.
  • ADVAIR DISKUS should not be used more often than recommended, at higher doses than recommended, or in conjunction with other medicines containing LABA, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. Patients using ADVAIR DISKUS should not use another medicine containing a LABA (e.g., salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol, vilanterol) for any reason.
  • Oropharyngeal candidiasis has occurred in patients treated with ADVAIR DISKUS. Advise patients to rinse the mouth with water without swallowing following inhalation to help reduce the risk of oropharyngeal candidiasis.
  • Patients who use corticosteroids are at risk for potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. A more serious or even fatal course of chickenpox or measles may occur in susceptible patients. Use caution in patients with the above because of the potential for worsening of these infections.
  • Particular care is needed for patients who have been transferred from systemically active corticosteroids to inhaled corticosteroids because deaths due to adrenal insufficiency have occurred in patients with asthma during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids.  Slowly taper the dose of systemic corticosteroids if transferring patients to ADVAIR DISKUS.
  • Hypercorticism and adrenal suppression may occur with high doses of inhaled corticosteroids, including fluticasone propionate, or at the recommended dose in susceptible individuals. If such effects occur, discontinue ADVAIR DISKUS slowly.
  • The use of strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with ADVAIR DISKUS is not recommended because increased systemic corticosteroid and increased cardiovascular adverse effects may occur.
  • If paradoxical bronchospasm occurs, discontinue ADVAIR DISKUS immediately and institute alternative therapy.
  • Salmeterol, a component of ADVAIR DISKUS, can produce a clinically significant cardiovascular effect in some patients as measured by pulse rate, blood pressure, and/or symptoms. If such effects occur, ADVAIR DISKUS may need to be discontinued. ADVAIR DISKUS should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
  • Decreases in bone mineral density (BMD) have been observed with long-term administration of products containing inhaled corticosteroids. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids) should be monitored and treated with established standards of care.
  • Inhaled corticosteroids, as well as poorly controlled asthma, may cause a reduction in growth velocity, and the long-term effect on final adult height is unknown. Patients should be maintained on the lowest dose of inhaled corticosteroid that effectively controls their asthma. Monitor growth of pediatric patients.
  • Glaucoma, increased intraocular pressure, and cataracts have been reported in patients with asthma and COPD following the long‐term administration of inhaled corticosteroids, including fluticasone propionate, a component of ADVAIR DISKUS. Therefore, close monitoring is warranted in patients with a change in vision or with a history of increased intraocular pressure, glaucoma, and/or cataracts.
  • Be alert to hypokalemia, hyperglycemia, and systemic eosinophilic conditions, such as Churg-Strauss syndrome.
  • Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines.

ADVERSE REACTIONS

  • Most common adverse reactions (incidence ≥3%) in subjects with asthma taking ADVAIR DISKUS 100/50, ADVAIR DISKUS 250/50, and placebo, respectively, were upper respiratory tract infection (27%, 21%, 14%), pharyngitis (13%, 10%, 6%), upper respiratory inflammation (7%, 6%, 5%), sinusitis (4%, 5%, 4%), hoarseness/dysphonia (5%, 2%, <1%), oral candidiasis (1%, 4%, 0%), viral respiratory infections (4%, 4%, 3%), bronchitis (2%, 8%, 2%), cough (3%, 6%, 2%), headaches (12%, 13%, 7%), nausea and vomiting (4%, 6%, 1%), gastrointestinal discomfort and pain (4%, 1%, 1%), diarrhea (4%, 2%, 1%), viral gastrointestinal infections (3%, 0%, 2%), candidiasis unspecified site (3%, 0%, 1%), and musculoskeletal pain (4%, 2%, 3%). The types of adverse reactions and events reported were similar in subjects treated with ADVAIR DISKUS 500/50.

DRUG INTERACTIONS

  • The use of strong cytochrome P450 3A4 (CYP3A4) inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with ADVAIR DISKUS is not recommended because increased systemic corticosteroid and increased cardiovascular adverse effects may occur.
  • ADVAIR DISKUS should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents, because the action of salmeterol, a component of ADVAIR DISKUS, on the vascular system may be potentiated by these agents.
  • Use beta-blockers with caution as they not only block the pulmonary effect of beta-agonists, such as salmeterol, a component of ADVAIR DISKUS, but may also produce severe bronchospasm in patients with asthma or COPD.
  • Use ADVAIR DISKUS with caution in patients taking non–potassium-sparing diuretics (such as loop or thiazide diuretics), as electrocardiographic changes and/or hypokalemia associated with non–potassium-sparing diuretics may worsen with coadministration with beta-agonists, such as salmeterol.

USE IN SPECIFIC POPULATIONS

  • Fluticasone propionate and salmeterol are predominantly cleared by hepatic metabolism. Impairment of liver function may lead to accumulation of fluticasone propionate and salmeterol in plasma. Therefore, patients with hepatic disease should be closely monitored.

RELVAR®, BREO®,ANORO®, NUCALA®, SERETIDE®, ELLIPTA® and DISKUS® are trade marks of the GlaxoSmithKline group of companies.

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+44 (0) 20 8047 2406

(London)

 

Jeff McLaughlin

+1 215 751 7002

(Philadelphia)

Cautionary statement regarding forward-looking statements

GSK cautions investors that any forward-looking statements or projections made by GSK, including those made in this announcement, are subject to risks and uncertainties that may cause actual results to differ materially from those projected. Such factors include, but are not limited to, those described under Item 3.D 'Risk factors' in the company's Annual Report on Form 20-F for 2015.