- ACRONYMS AND DEFINITIONS
- Anticholinergic = Antimuscarinic
- ICS - Inhaled corticosteroid
- LABA - Long-acting beta agonist
- LAMA - Long-acting muscarinic antagonist
- NHLBI - National Heart, Lung, and Blood Institute
- RCT - Randomized controlled trial
- SABA - Short-acting beta agonist
- SAMA - Short-acting muscarinic antagonist
- SHORT-ACTING MUSCARINIC ANTAGONISTS
Ipratropium (Atrovent®)
Dosage forms
HFA Inhaler
- Delivers 17 mcg of ipratropium per actuation (200 actuations per inhaler)
Nebulizer
- Ipratropium 0.02% (0.5 mg/2.5 ml)
- Comes in package of 25 nebs
Dosing - COPD
HFA inhaler
- Two puffs four times a day
- Max: 12 puffs in 24 hours
Nebulizer
- One neb every 6 - 8 hours
Dosing - Asthma Exacerbations
Generic / Price
- Atrovent HFA® - NO/$$$$
- Ipratropium nebs (25 nebs) - YES/$
Other
Atrovent HFA®
- Does not require shaking
- Prime before first use by releasing 2 test sprays
- Re-prime inhaler if not used for more than 3 days
- Avoid spraying in eyes
Nebulizer
- May mix with albuterol. Use within one hour after mixing.
- Protect nebs from sunlight
Mechanism of action
- Anticholinergic - blocks muscarinic receptors on bronchial smooth muscle and reduces intrinsic vagal tone of the airway
FDA-approved indication
- Chronic Obstructive Pulmonary Disease (COPD)
- NHLBI 2007 asthma guidelines state that anticholinergic agents provide additive benefit to SABA in moderate-to-severe asthma exacerbations, and may be used as an alternative bronchodilator for patients who do not tolerate SABA
Side effects
Side effect | Ipratropium | Placebo |
---|---|---|
Bronchitis | 10% | 6% |
Shortness of breath | 8% | 4% |
Dizziness | 3% | 2% |
Dry mouth | 4% | 2% |
Nausea | 4% | 2% |
Anticholinergic side effects
|
Drug interactions
- Anticholinergic medications - may potentiate anticholinergic side effects
- OCT2 substrates - ipratropium is an OCT2 inhibitor
Contraindications / Precautions
- Glaucoma - ipratropium may cause pupil dilation which can precipitate or worsen narrow-angle glaucoma
- Paradoxical bronchospasm - paradoxical bronchospasm has occurred in some patients
- Benign prostatic hypertrophy (BPH) - ipratropium may worsen urinary retention seen in BPH
- Liver disease - has not been studied extensively
- Kidney disease - has not been studied extensively
- LONG-ACTING MUSCARINIC ANTAGONIST
Aclidinium (Tudorza Pressair®)
Dosage forms
Inhaler
- Delivers 400 mcg of aclidinium inhalation powder per actuation
- Comes in inhaler with 30 or 60 doses
Dosing
COPD
- One inhalation twice a day
- Discard inhaler 45 days after opening pouch
Efficacy
Generic / Price
- NO/$$$$Mechanism of action
- Anticholinergic - blocks muscarinic receptors on bronchial smooth muscle and reduces intrinsic vagal tone of the airway
FDA-approved indication
- Chronic Obstructive Pulmonary Disease (COPD)
- Aclidinium is NOT indicated to treat acute bronchospasm
Side effects
Side effect | Aclidinium | Placebo |
---|---|---|
Headache | 6.6% | 5% |
Nasopharyngitis | 5.5% | 3.9% |
Cough | 3% | 2.2% |
Diarrhea | 2.7% | 1.4% |
Sinusitis | 1.7% | 0.8% |
Rhinitis | 1.6% | 1.2% |
Anticholinergic side effects
|
Drug interactions
- Anticholinergic medications - may potentiate anticholinergic side effects
Contraindications / Precautions
- Severe allergy to milk proteins - DO NOT USE. Contains lactose.
- Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis have occurred
- Glaucoma - aclidinium may cause pupil dilation which can precipitate or worsen narrow-angle glaucoma
- Paradoxical bronchospasm - paradoxical bronchospasm has occurred in some patients
- Benign prostatic hypertrophy (BPH) - aclidinium may worsen urinary retention seen in BPH
- Liver disease - has not been studied extensively
- Kidney disease - no dose adjustment necessary
Revefenacin (Yupelri®)
Dosage forms
Inhalation solution
- 175 mcg/3 ml vial
- Comes in carton with 30 vials
Dosing
COPD
- Dosing: One 175 mcg unit-dose vial once daily via nebulizer
- Do not mix with other nebulized medications
Efficacy
Generic / Price
- NO/$$$$Mechanism of action
- Anticholinergic - blocks muscarinic receptors on bronchial smooth muscle and reduces intrinsic vagal tone of the airway
FDA-approved indication
- Chronic Obstructive Pulmonary Disease (COPD)
- Revefenacin is NOT indicated to treat acute bronchospasm
Side effects
- NOTE: Only side effects that occurred at an overall incidence of ≥ 2% and more than placebo are listed
Side effect | Revefenacin (N=395) |
Placebo (N=418) |
---|---|---|
Cough | 4% | 4% |
Nasopharyngitis | 4% | 2% |
Upper respiratory tract infection | 3% | 2% |
Headache | 4% | 3% |
Back pain | 2% | 1% |
Anticholinergic side effects
|
Drug interactions
- Anticholinergic medications - may potentiate anticholinergic side effects
- OATP1B1/B3 inhibitors - DO NOT COMBINE. The active metabolite of revefenacin is an OATP1B1/B3 substrate and exposure is increased.
Contraindications / Precautions
- Hypersensitivity reactions - hypersensitivity reactions including anaphylaxis have occurred
- Glaucoma - revefenacin may cause pupil dilation which can precipitate or worsen narrow-angle glaucoma
- Paradoxical bronchospasm - paradoxical bronchospasm has occurred in some patients
- Benign prostatic hypertrophy (BPH) - revefenacin may worsen urinary retention seen in BPH
- Liver disease - has not been studied. Not recommended.
- Kidney disease - no dose adjustment necessary. Monitor for systemic antimuscarinic side effects in patients with severe renal impairment.
Tiotropium | Spiriva® Handihaler | Spiriva® Respimat
Dosage forms
Spiriva® Handihaler
- Delivers 18 mcg of tiotropium inhalation powder per actuation
- Comes in carton with 30 or 90 capsules
Spiriva® Respimat
- Comes in two doses:
- Tiotropium 1.25 mcg/actuation
- Tiotropium 2.5 mcg/actuation
- Carton contains cartridge and inhaler
- Cartridge contains 60 metered sprays
Dosing - Handihaler
COPD
- One capsule once daily
- Two inhalations should be taken from device for each capsule
- May store at room temperature
- Use capsule immediately after removing from blister pack
Dosing - Respimat
COPD
- Two inhalations (5 mcg total) once daily
- Use 2.5 mcg inhaler in COPD
Asthma (≥ 6 years old)
- Two inhalations (2.5 mcg total) once daily
- Use 1.25 mcg inhaler in Asthma
- May take up to 8 weeks before full benefit is seen
Generic / Price
- NO/$$$$Mechanism of action
- Anticholinergic - blocks muscarinic receptors on bronchial smooth muscle and reduces intrinsic vagal tone of the airway
FDA-approved indications
Spiriva® Handihaler
- Chronic Obstructive Pulmonary Disease (COPD) - long-term maintenance and prevention of COPD exacerbations
- Tiotropium is NOT indicated to treat acute bronchospasm
Spiriva® Respimat
- Chronic Obstructive Pulmonary Disease (COPD) - tiotropium is indicated for long-term maintenance and prevention of COPD exacerbations
- Asthma - maintenance treatment of asthma in patients 6 years of age and older
- Tiotropium is NOT indicated to treat acute bronchospasm
Side effects
Side effect | Spiriva Handihaler | Placebo |
---|---|---|
Upper Respiratory infection | 41% | 37% |
Dry mouth | 16% | 3% |
Sinusitis | 11% | 9% |
Pharyngitis | 9% | 7% |
Chest pain | 7% | 5% |
Urinary tract infection | 7% | 5% |
Shortness of breath | 6% | 5% |
Abdominal pain | 5% | 3% |
Anticholinergic side effects
|
Side effect | Spiriva Respimat | Placebo |
---|---|---|
Pharyngitis | 11.5% | 10.1% |
Cough | 5.8% | 5.5% |
Dry mouth | 4.1% | 1.6% |
Sinusitis | 3.1% | 2.7% |
Anticholinergic side effects
|
Drug interactions
- Anticholinergic medications - may potentiate anticholinergic side effects
Contraindications / Precautions
- Severe allergy to milk proteins (Handihaler® only) - DO NOT USE. Contains lactose.
- Glaucoma - tiotropium may cause pupil dilation which can precipitate or worsen narrow-angle glaucoma
- Paradoxical bronchospasm - paradoxical bronchospasm has occurred in some patients
- Benign prostatic hypertrophy (BPH) - ipratropium may worsen urinary retention seen in BPH
- Liver disease - has not been studied extensively
- Kidney disease - CrCl ≤ 60 ml/min - monitor patient closely for anticholinergic side effects
Umeclidinium (Incruse Ellipta®)
Dosage forms
Inhaler
- Delivers 62.5 mcg of umeclidinium inhalation powder per actuation
- Comes in package with 30 doses
Dosing
COPD
- One inhalation once daily
- Inhale at the same time each day
- Discard inhaler 6 weeks after opening foil pouch
Generic / Price
- NO/$$$$Mechanism of action
- Anticholinergic - blocks muscarinic receptors on bronchial smooth muscle and reduces intrinsic vagal tone of the airway
FDA-approved indications
- Chronic Obstructive Pulmonary Disease (COPD)
- Umeclidinium is NOT indicated to treat acute bronchospasm
Side effects
Side effect | Umeclidinium | Placebo |
---|---|---|
Nasopharyngitis | 8% | 7% |
Upper respiratory infection | 5% | 4% |
Cough | 3% | 2% |
Arthralgia | 2% | 1% |
Anticholinergic side effects
|
Drug interactions
- Anticholinergic medications - may potentiate anticholinergic side effects
Contraindications / Precautions
- Severe allergy to milk proteins - DO NOT USE. Contains lactose.
- Glaucoma - umeclidinium may cause pupil dilation which can precipitate or worsen narrow-angle glaucoma
- Paradoxical bronchospasm - paradoxical bronchospasm has occurred in some patients
- Benign prostatic hypertrophy (BPH) - umeclidinium may worsen urinary retention seen in BPH
- Kidney disease - no dose adjustment necessary
- Liver disease
- Mild-to-moderate (Child-Pugh A/B): no dose adjustment necessary
- Severe (Child-Pugh C): has not been studied
- SAMA + SABA
Combivent Respimat® | Duoneb® | Albuterol + Ipratropium
Dosage forms
Inhaler (Combivent Respimat®)
- Inhaler delivers 100 mcg of albuterol and 20 mcg of ipratropium per actuation
- Each inhaler contains 120 actuations
Nebulizer solution (Duoneb®)
- Ipratropium 0.5 mg/Albuterol 3 mg per 3 ml neb
- Comes in box of 30 or 60 nebs
Dosing - Respimat
Acute bronchospasm in COPD
- Dosing: One inhalation four times a day with up to two additional inhalations if required
- Max: Six inhalations in 24 hours
Acute asthma exacerbation
Dosing - Duoneb
Acute bronchospasm in COPD
- Dosing: One neb four times a day with up to two additional nebs if required
- Max: Six nebs in 24 hours
Acute asthma exacerbation
Generic / Price
- Combivent Respimat® - NO/$$$$
- Duoneb® - YES/$
Other
- Combivent Respimat® is good for 3 months after first use
- See Combivent Respimat® patient insert for priming instructions
FDA-approved indications
- Chronic Obstructive Pulmonary Disease (COPD)
- Relief of bronchospasm
- LAMA + LABA
Anoro Ellipta® (Vilanterol + Umeclidinium)
Dosage forms
Inhalation powder
- Each powder inhalation contains umeclidinium 62.5 mcg and vilanterol 25 mcg
- Inhaler comes with 30 inhalations
Dosing
COPD
- One inhalation once daily
Generic / Price
- NO/$$$$Other
- See Anoro Ellipta® PI for complete prescribing information
- Discard inhaler 6 weeks after opening the foil tray
- DO NOT USE in patients with severe milk allergy
- Vilanterol is a CYP3A4 substrate. Use caution with strong CYP3A4 inhibitors.
- DO NOT USE in patients with congenital long QT syndrome [4]
FDA-approved indications
- Maintenance treatment of Chronic Obstructive Pulmonary Disease (COPD)
- NOT for relief of acute bronchospasm
Bevespi Aerosphere™ (Formoterol + Glycopyrrolate)
Dosage forms
Inhalation aerosol
- Device delivers 4.8 mcg of formoterol and 9 mcg of glycopyrrolate per actuation
- Each inhaler contains 120 inhalations
Dosing
COPD
- Two inhalations twice a day
Generic / Price
- NO/$$$$Other
- Inhaler must be primed. See package insert for instructions.
- See Bevespi Aerosphere PI for complete prescribing information
- Inhaler is good for 3 months after removal from foil pouch
FDA-approved indications
- Chronic Obstructive Pulmonary Disease (COPD)
- NOT for relief of acute bronchospasm
Duaklir Pressair® (Aclidinium + Formoterol)
Dosage forms
Inhalation powder
- Device delivers 400 mcg of aclidinium and 12 mcg of formoterol powder per actuation
- Comes in 30 dose and 60 dose inhaler
- Inhaler is breath-actuated
Dosing
COPD
- One inhalation twice a day
Generic / Price
- NO/$$$$Other
- Do not use in patients with severe milk allergy. Contains lactose.
- Inhaler is good for 2 months after removing from sealed bag
FDA-approved indications
- Chronic Obstructive Pulmonary Disease (COPD)
- NOT for relief of acute bronchospasm
Stiolto® Respimat (Olodaterol + Tiotropium)
Dosage forms
Inhalation spray
- Inhaler delivers tiotropium 3.124 mcg (equivalent to 2.5 mcg tiotropium) and olodaterol 2.736 mcg (equivalent to 2.5 mcg olodaterol) per spray
- Inhaler comes with 60 actuations
Dosing
COPD
- Two inhalations once daily
- Use at the same time every day
Generic - NO/$$$$
Other
- See Stiolto® PI for complete prescribing information
- Inhaler should be primed. See patient instructions for details
FDA-approved indications
- Maintenance treatment of Chronic Obstructive Pulmonary Disease (COPD)
- NOT for relief of acute bronchospasm
- LABA + LAMA + ICS
Breztri Aerosphere™ (budesonide + glycopyrrolate + formoterol)
Dosage forms
Inhalation aerosol
- Inhaler delivers 160 mcg of budesonide, 9 mcg of glycopyrrolate, and 4.8 mcg of formoterol per inhalation
- Inhaler comes with 120 inhalations
Dosing
COPD
- Two inhalations twice daily
Generic / Price
- NO/$$$$FDA-approved indication
- Maintenance treatment of Chronic Obstructive Pulmonary Disease (COPD)
- NOT for relief of acute bronchospasm
Trelegy Ellipta® (fluticasone + umeclidinium + vilanterol)
Dosage forms
Inhalation powder
- Fluticasone / Umeclidinium / Vilanterol
- 100 mcg/62.5 mcg/25 mcg
- 200 mcg/62.5 mcg/25 mcg
- Inhaler comes with 30 inhalations
Dosing
COPD
- One inhalation once daily of 100/62.5/25 mcg
Asthma (adults)
- One inhalation once daily of 100/62.5/25 mcg or 200/62.5/25 mcg
- When choosing a dose consider disease severity and current dose of ICS
Generic / Price
- NO/$$$$Other
- See Trelegy Ellipta® PI for complete prescribing information
- Discard inhaler 6 weeks after opening the foil tray
- DO NOT USE in patients with severe milk allergy
- Vilanterol is a CYP3A4 substrate. Use caution with strong CYP3A4 inhibitors.
FDA-approved indication
- Chronic Obstructive Pulmonary Disease (COPD) - maintenance treatment
- Asthma - maintenance treatment in adults
- NOT for relief of acute bronchospasm
- NHLBI ASTHMA EXACERBATION TREATMENT RECOMMENDATIONS
- PRICE ($) INFO
Pricing legend
- $ = 0 - $50
- $$ = $51 - $100
- $$$ = $101 - $150
- $$$$ = > $151
- Pricing based on one month of therapy at standard dosing in an adult
- Pricing based on information from GoodRX.com®
- Pricing may vary by region and availability
Patient Assistance Programs for Inhaled Antimuscarinics | ||||
---|---|---|---|---|
Drug | Manufacturer | Ships to | PAP info | Application |
Anoro Ellipta® (vilanterol + umeclidinium) | GlaxoSmithKline | Patient or other | Link | Link |
Atrovent® HFA (ipratropium) | Boehringer Ingelheim | Patient | Link | Link |
Bevespi Aerosphere® (formoterol + glycopyrrolate) | AstraZeneca | Patient or doctor | Link | Link |
Combivent® (albuterol + ipratropium) | Boehringer Ingelheim | Patient | Link | Link |
Duaklir Pressair® (aclidinium + formoterol) | Circassia | N/A | N/A | N/A |
Incruse Ellipta® (umeclidinium) | GlaxoSmithKline | Patient or other | Link | Link |
Spiriva® handihaler and Respimat (tiotropium) | Boehringer Ingelheim | Patient | Link | Link |
Stiolto Respimat® (olodaterol + tiotropium) | Boehringer Ingelheim | Patient | Link | Link |
Trelegy Ellipta® (fluticasone + umeclidinium + vilanterol) | GlaxoSmithKline | Patient or other | Link | Link |
Tudorza Pressair® (aclidinium) | Circassia | N/A | N/A | N/A |
Yupelri® (revefenacin) | Mylan | N/A | N/A | N/A |
- BIBLIOGRAPHY
- 1 - NHLBI 2007 asthma guidelines
- 2 - Manufacturer's package insert