Adverse reactions from 6-month studies

The incidence of adverse reactions (≥1% and more common than placebo) associated with ANORO is based on four 6-month studies: 2 placebo-controlled studies and 2 active-controlled studies

12-month study: In a long-term safety study, subjects (n=335) were treated for up to 12 months with UMEC/VI 125 mcg/25 mcg or placebo. Adverse reactions that occurred with a frequency of ≥1% in the group receiving UMEC/VI 125 mcg/25 mcg that exceeded that in placebo in this study were:

  • headache
  • back pain
  • sinusitis
  • cough
  • urinary tract infection
  • arthralgia
  • nausea
  • vertigo
  • abdominal pain
  • pleuritic pain
  • viral respiratory tract infection
  • toothache
  • diabetes mellitus

UMEC=umeclidinium; VI=vilanterol.

Indication for ANORO ELLIPTA

ANORO is for the once-daily maintenance treatment of airflow obstruction in patients with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and/or emphysema. ANORO is NOT for the relief of acute bronchospasm or for asthma.

WARNING: ASTHMA-RELATED DEATH

  • Long-acting beta2-adrenergic agonists (LABA), such as vilanterol, one of the active ingredients in ANORO, 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.
  • The safety and efficacy of ANORO in patients with asthma have not been established. ANORO is not indicated for the treatment of asthma.

CONTRAINDICATIONS

  • ANORO is contraindicated in patients with severe hypersensitivity to milk proteins or with hypersensitivity to umeclidinium, vilanterol, or any of the excipients.

WARNINGS AND PRECAUTIONS

  • ANORO should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD.
  • ANORO is NOT a rescue medication and should NOT be used for the relief of acute bronchospasm or symptoms. Acute symptoms should be treated with an inhaled, short-acting beta2-agonist.
  • ANORO should not be used more often or at higher doses than recommended or with another LABA (eg, salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs, like LABA.
  • Caution should be exercised when considering the coadministration of ANORO with long-term ketoconazole and other known strong CYP3A4 inhibitors (eg, ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, saquinavir, telithromycin, troleandomycin, voriconazole) because increased cardiovascular adverse effects may occur.
  • If paradoxical bronchospasm occurs, discontinue ANORO and institute alternative therapy.
  • Hypersensitivity reactions such as anaphylaxis, angioedema, rash, and urticaria may occur after administration of ANORO. Discontinue ANORO if such reactions occur.
  • Vilanterol can produce clinically significant cardiovascular effects in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, or symptoms. If such effects occur, ANORO may need to be discontinued. ANORO should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
  • Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines.
  • Use with caution in patients with narrow-angle glaucoma. Instruct patients to contact a healthcare provider immediately if signs or symptoms of acute narrow-angle glaucoma develop.
  • Use with caution in patients with urinary retention, especially in patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to contact a healthcare provider immediately if signs or symptoms of urinary retention develop.
  • Be alert to hypokalemia and hyperglycemia.

ADVERSE REACTIONS

  • The most common adverse reactions (≥1% and more common than placebo) reported in four 6-month clinical trials with ANORO (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, 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.

DRUG INTERACTIONS

  • Caution should be exercised when considering the coadministration of ANORO with ketoconazole and other known strong CYP3A4 inhibitors as increased systemic exposure to vilanterol and cardiovascular adverse effects may occur. See prior Warning and Precaution regarding CYP3A4 inhibitors.
  • ANORO 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 they may potentiate the effect of vilanterol on the cardiovascular system.
  • Use beta-blockers with caution as they not only block the pulmonary effect of beta-agonists, such as vilanterol, but may produce severe bronchospasm in patients with COPD.
  • Use with caution in patients taking non–potassium-sparing diuretics, as ECG changes and/or hypokalemia associated with these diuretics may worsen with concomitant beta-agonists.
  • Avoid coadministration of ANORO with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects.

WARNING: ASTHMA-RELATED DEATH

  • Long-acting beta2-adrenergic agonists (LABA), such as vilanterol, one of the active ingredients in ANORO, 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.
  • The safety and efficacy of ANORO in patients with asthma have not been established. ANORO is not indicated for the treatment of asthma.

CONTRAINDICATIONS

  • ANORO is contraindicated in patients with severe hypersensitivity to milk proteins or with hypersensitivity to umeclidinium, vilanterol, or any of the excipients.

WARNINGS AND PRECAUTIONS

  • ANORO should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD.
  • ANORO is NOT a rescue medication and should NOT be used for the relief of acute bronchospasm or symptoms. Acute symptoms should be treated with an inhaled, short-acting beta2-agonist.
  • ANORO should not be used more often or at higher doses than recommended or with another LABA (eg, salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs, like LABA.
  • Caution should be exercised when considering the coadministration of ANORO with long-term ketoconazole and other known strong CYP3A4 inhibitors (eg, ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, saquinavir, telithromycin, troleandomycin, voriconazole) because increased cardiovascular adverse effects may occur.
  • If paradoxical bronchospasm occurs, discontinue ANORO and institute alternative therapy.
  • Hypersensitivity reactions such as anaphylaxis, angioedema, rash, and urticaria may occur after administration of ANORO. Discontinue ANORO if such reactions occur.
  • Vilanterol can produce clinically significant cardiovascular effects in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, or symptoms. If such effects occur, ANORO may need to be discontinued. ANORO should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
  • Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines.
  • Use with caution in patients with narrow-angle glaucoma. Instruct patients to contact a healthcare provider immediately if signs or symptoms of acute narrow-angle glaucoma develop.
  • Use with caution in patients with urinary retention, especially in patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to contact a healthcare provider immediately if signs or symptoms of urinary retention develop.
  • Be alert to hypokalemia and hyperglycemia.

ADVERSE REACTIONS

  • The most common adverse reactions (≥1% and more common than placebo) reported in four 6-month clinical trials with ANORO (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, 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.

DRUG INTERACTIONS

  • Caution should be exercised when considering the coadministration of ANORO with ketoconazole and other known strong CYP3A4 inhibitors as increased systemic exposure to vilanterol and cardiovascular adverse effects may occur. See prior Warning and Precaution regarding CYP3A4 inhibitors.
  • ANORO 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 they may potentiate the effect of vilanterol on the cardiovascular system.
  • Use beta-blockers with caution as they not only block the pulmonary effect of beta-agonists, such as vilanterol, but may produce severe bronchospasm in patients with COPD.
  • Use with caution in patients taking non–potassium-sparing diuretics, as ECG changes and/or hypokalemia associated with these diuretics may worsen with concomitant beta-agonists.
  • Avoid coadministration of ANORO with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects.

WARNING: ASTHMA-RELATED DEATH

  • Long-acting beta2-adrenergic agonists (LABA), such as vilanterol, one of the active ingredients in ANORO, 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.
  • The safety and efficacy of ANORO in patients with asthma have not been established. ANORO is not indicated for the treatment of asthma.

CONTRAINDICATIONS

  • ANORO is contraindicated in patients with severe hypersensitivity to milk proteins or with hypersensitivity to umeclidinium, vilanterol, or any of the excipients.

WARNINGS AND PRECAUTIONS

  • ANORO should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD.
  • ANORO is NOT a rescue medication and should NOT be used for the relief of acute bronchospasm or symptoms. Acute symptoms should be treated with an inhaled, short-acting beta2-agonist.
  • ANORO should not be used more often or at higher doses than recommended or with another LABA (eg, salmeterol, formoterol fumarate, arformoterol tartrate, indacaterol) for any reason, as an overdose may result. Clinically significant cardiovascular effects and fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs, like LABA.
  • Caution should be exercised when considering the coadministration of ANORO with long-term ketoconazole and other known strong CYP3A4 inhibitors (eg, ritonavir, clarithromycin, conivaptan, indinavir, itraconazole, lopinavir, nefazodone, nelfinavir, saquinavir, telithromycin, troleandomycin, voriconazole) because increased cardiovascular adverse effects may occur.
  • If paradoxical bronchospasm occurs, discontinue ANORO and institute alternative therapy.
  • Hypersensitivity reactions such as anaphylaxis, angioedema, rash, and urticaria may occur after administration of ANORO. Discontinue ANORO if such reactions occur.
  • Vilanterol can produce clinically significant cardiovascular effects in some patients as measured by increases in pulse rate, systolic or diastolic blood pressure, or symptoms. If such effects occur, ANORO may need to be discontinued. ANORO should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
  • Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis, and in patients who are unusually responsive to sympathomimetic amines.
  • Use with caution in patients with narrow-angle glaucoma. Instruct patients to contact a healthcare provider immediately if signs or symptoms of acute narrow-angle glaucoma develop.
  • Use with caution in patients with urinary retention, especially in patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to contact a healthcare provider immediately if signs or symptoms of urinary retention develop.
  • Be alert to hypokalemia and hyperglycemia.

ADVERSE REACTIONS

  • The most common adverse reactions (≥1% and more common than placebo) reported in four 6-month clinical trials with ANORO (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, 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.

DRUG INTERACTIONS

  • Caution should be exercised when considering the coadministration of ANORO with ketoconazole and other known strong CYP3A4 inhibitors as increased systemic exposure to vilanterol and cardiovascular adverse effects may occur. See prior Warning and Precaution regarding CYP3A4 inhibitors.
  • ANORO 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 they may potentiate the effect of vilanterol on the cardiovascular system.
  • Use beta-blockers with caution as they not only block the pulmonary effect of beta-agonists, such as vilanterol, but may produce severe bronchospasm in patients with COPD.
  • Use with caution in patients taking non–potassium-sparing diuretics, as ECG changes and/or hypokalemia associated with these diuretics may worsen with concomitant beta-agonists.
  • Avoid coadministration of ANORO with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects.

Important Safety Information for
INCRUSE ELLIPTA

CONTRAINDICATIONS

  • The use of INCRUSE ELLIPTA is contraindicated in patients with severe hypersensitivity to milk proteins or who have hypersensitivity to umeclidinium or any of the excipients.

WARNINGS AND PRECAUTIONS

  • INCRUSE ELLIPTA should not be initiated in patients during rapidly deteriorating or potentially life-threatening episodes of COPD.
  • INCRUSE ELLIPTA should not be 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.
  • If paradoxical bronchospasm occurs, discontinue INCRUSE ELLIPTA and institute alternative therapy.
  • Use with caution in patients with narrow-angle glaucoma. Instruct patients to contact a healthcare provider immediately if signs or symptoms of acute narrow-angle glaucoma develop.
  • Use with caution in patients with urinary retention, especially in patients with prostatic hyperplasia or bladder-neck obstruction. Instruct patients to contact a healthcare provider immediately if signs or symptoms of urinary retention develop.

ADVERSE REACTIONS

  • The most common adverse reactions (≥1% and more common than placebo) reported in one 12-week and one 24-week clinical trial with INCRUSE ELLIPTA as monotherapy (and placebo) were: nasopharyngitis, 8% (7%); upper respiratory tract infection, 5% (4%); pharyngitis, 1% (<1%); viral upper respiratory tract infection, 1% (<1%); cough, 3% (2%); arthralgia, 2% (1%); myalgia, 1% (<1%); upper abdominal pain, 1% (<1%); toothache, 1% (<1%); contusion, 1% (<1%); tachycardia, 1% (<1%). Other adverse reactions with INCRUSE ELLIPTA observed with an incidence <1% but more common than placebo included atrial fibrillation.
  • In addition to the two placebo-controlled clinical trials with INCRUSE ELLIPTA, a 12-month trial evaluated the safety of umeclidinium 125 mcg in subjects with COPD. Adverse reactions (incidence ≥1% and exceeded that in placebo) in subjects receiving umeclidinium 125 mcg as monotherapy were: nasopharyngitis, upper respiratory tract infection, urinary tract infection, pharyngitis, pneumonia, lower respiratory tract infection, rhinitis, supraventricular tachycardia, supraventricular extrasystoles, sinus tachycardia, idioventricular rhythm, headache, dizziness, sinus headache, cough, back pain, arthralgia, pain in extremity, neck pain, myalgia, nausea, dyspepsia, diarrhea, rash, depression, and vertigo.
  • In addition to the adverse reactions reported in the umeclidinium monotherapy trials, adverse reactions reported in four 12-week trials with INCRUSE ELLIPTA in combination with an inhaled corticosteroid/long-acting beta2-adrenergic agonist (ICS/LABA), at an incidence of ≥1% and exceeding ICS/LABA alone, were oropharyngeal pain and dysgeusia.

DRUG INTERACTIONS

  • Avoid coadministration of INCRUSE ELLIPTA with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects.