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Inhaled Respiratory Medications:How to Simplify Inhaled Medication Regimens and
Discuss Medication Changes with Patients
Stephanie Cheng, PharmD, MPH, BCGPSeptember 23, 2021
Learning Objectives
• Be able to list at least 3 major adverse effects of inhaled medications
• Be able to identify the different inhaled medications into their proper medication classes
• Be able to identify duplicate therapies in a patient’s respiratory medication regimen
• Be able to state the risk and rational of using or not using corticosteroids in the hospice population
• Be able to discuss inhaled medication changes with patients
• Be able to list the steps to appropriately manage dyspnea in a hospice patient
Inhaled Respiratory Drugs
Beta 2 Agonists• Binds to beta-2 receptors• Relaxation of smooth muscles in the lung• Dilation and opening of airways
Muscarinic Antagonists• Inhibits acetylcholine in bronchial smooth muscle• Bronchodilation
Corticosteroids• Inhibits the inflammatory response
Can be mixed and matched
in various combinations
3 Main Categories
Reference: Lexicomp
Adverse Effects of Inhaled MedicationsDrug Category Adverse Effects
Beta 2 agonistsTachycardia (up to 200 beats/minute), arrhythmias,
nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, sleeplessness,
hypertension or hypotension
Muscarinic antagonists
Dizziness, headache, dry mouth, dyspepsia, nausea, UTI, urinary retention, constipation
Corticosteroids Increase risk of upper respiratory tract infections, headache, pharyngitis
• Try to avoid adverse effects by removing duplicate therapies– For PRN therapy, the patient should only be on a regimen that contains one
beta 2 agonist and/or one muscarinic antagonist.– For Routine therapy, the patient does not have to have something from all 3
categories, but if they are on something, they should only have oneof that type of medication on board.
Reference: Lexicomp
Dosage Forms
• Handheld Inhaler– Metered dose inhaler (MDI)– Dry powder inhaler (DPI)– Aerolizers– HandiHaler– Twisthaler– Flexhaler
• Nebulized solution
• Oral tablet (Albuterol tablet, corticosteroid: prednisone)
• Beta 2 agonists and muscarinic antagonists– Short-acting and long-acting formulations
Handheld inhalers
• Require adequate inhalation force• Require coordination to use• Are generally more expensive
compared to the nebulized solution
Reference: Lexicomp
Inhalers
• More than 8 out of 10 patients with obstructive lung disease in the US experience inhaler use-related errors
– Patients with end-stage pulmonary disease/advance age have a greater likelihood of errors
• Incorrect inhaler technique prevents patients from receiving optimal benefit from their inhalers
• Nebulized medications tends to be a more efficient route of administration
• Switching inhaled corticosteroids to oral corticosteroids may provide palliation of additional symptoms including suppressed appetite, inflammatory pain, fatigue, and acute pulmonary exacerbations
Reference: NHPCO. Hospice Medication Deprescribing Toolkit. November 2020, Version 1.0
Inhaled Medications in Hospice Patients
• Determine the severity of the patient’s COPD or lung condition.
• If they are taking nebulized inhaled medications, they most likely do not have enough positive inhalation force to use handheld inhalers.
• Consider keeping the nebulized solutions and D/C the handheld inhalers.
• Hospice patients with a terminal diagnosis of COPD or lung cancer generally do not have enough positive inhalation force to use handheld devices and should be on nebulized therapy.
The combination therapy of using DuoNeb routinely and PRN, plus prednisone (if a steroid medication is needed) is the most cost-
effective therapy for hospice patients with a terminal diagnosis of COPD or lung cancer.
Inhaler Technique Assessment
Does the Patient Have Enough Inspiratory Flow?
Special Note Regarding COVID-19 and Inhaled Medications
• COVID positive patients– Reserve handheld inhalers for these patients if they are in a facility
• COVID negative patients– Transition to nebulized solutions if possible
Respiratory Medications NOT in Combination
Beta 2 AgonistsGENERIC NAME BRAND NAME DOSAGE FORM
Short-Acting Beta-2 Agonists (SABAs)
Albuterol HFA Ventolin, ProAir, Proventil HFA MDI
Levalbuterol HFA Xopenex HFA MDI
Albuterol AccuNeb Nebulizer
Levalbuterol Xopenex Nebulizer
Long-Acting Beta-2 Agonists (LABAs)
Indacaterol Arcapta Neohaler DPI
Olodaterol Striverdi Respimat MDI
Salmeterol Serevent Diskus DPI
Arformoterol Brovana Nebulizer
Formoterol Perforomist Nebulizer
Oral tablet
Albuterol
End in -terol
Inhaled Corticosteroids (ICS)GENERIC NAME BRAND NAME DOSAGE FORMBeclomethasone Qvar MDI Budesonide Pulmicort Flexhaler DPI Ciclesonide Alvesco MDI
Fluticasone Flovent HFA MDIFluticasone ArmonAir Digihaler MDIFluticasone Flovent Diskus DPI
Fluticasone Arnuity Ellipta DPI
Mometasone Asmanex Twisthaler DPI
Budesonide Pulmicort Respules Nebulizer
Prednisone Prednisone Tablet
End in -sone or
-nide
Muscarinic AntagonistsGENERIC NAME BRAND NAME DOSAGE FORMShort-Acting Muscarinic Antagonists (SAMAs)Ipratropium HFA Atrovent HFA MDIIpratropium N/A NebulizerLong-Acting Muscarinic Antagonists (LAMAs)Aclidinium Tudorza Pressair DPI
Tiotropium Spiriva Handihaler, Respimat DPI, MDI
Umeclidinium Incruse Ellipta DPIGlycopyrrolate Seebri Neohaler DPIGlycopyrrolate Lonhala Magnair NebulizerRevefenacin Yupelri Nebulizer
End in -ium
Respiratory Medications in Combination
All are long-acting except
for Combivent/ Duoneb
Generic Name Brand Name(s) Dosage Form
SAMA/SABA Combination
Ipratropium/albuterol Combivent MDI
Ipratropium/albuterol DuoNeb Neb
LAMA/LABA Combinations
Umeclidinium/vilanterol Anoro Ellipta DPI
Tiotropium/olodaterol Stiolto Respimat DPI
Glycopyrrolate/indacaterol Utibron Neohaler DPI
Glycopyrrolate/formoterol Bevespi Aerosphere DPI
Aclidinium/formoterol Duaklir Genuair DPI
ICS/LABA Combinations
Budesonide/formoterol Symbicort DPI
Fluticasone/salmeterolAdvair HFAAdvair DiskusWixela Inhub
MDIDPIDPI
Fluticasone/vilanterol Breo Ellipta DPI
Mometasone/formoterol Dulera MDI
ICS/LAMA/LABA Combinations
Fluticasone/umeclidinium/vilanterol Trelegy Ellipta DPI
Budesonide/glycopyrrolate/formoterol Breztri Aerosphere MDI
Beta-2 Agonists Not in Combination
Generic Name Brand Name(s) Dosage FormCost (AWP)
One inhaler Per day
Short-Acting Beta-2 Agonists (SABAs)
Albuterol HFAVentolin HFA, Proair HFA, Proventil HFA
MDI$60$86$96
$2$3$3
Levalbuterol HFA Xopenex HFA MDI $74 $3
Albuterol AccuNeb Nebulizer - $7
Levalbuterol Xopenex Nebulizer - $25
Long-Acting Beta-2 Agonists (LABAs)
Indacaterol Arcapta Neohaler DPI $309* $10*
Olodaterol Striverdi Respimat MDI $280* $9*
Salmeterol Serevent Diskus DPI $493* $16*
Arformoterol Brovana Nebulizer - $43
Formoterol Perforomist Nebulizer - $42
End in -terol
Reference: Lexicomp
*Brand Name only, no generic available
Muscarinic Antagonists Not in Combination
Generic Name Brand Name(s) Dosage FormCost (AWP)
One inhaler Per dayShort-Acting Muscarinic Antagonists (SAMAs)
Ipratropium HFA Atrovent HFA MDI $513* $17*
Ipratropium N/A Nebulizer - $7
Long-Acting Muscarinic Antagonists (LAMAs)
Aclidinium Tudorza Pressair DPI $343* $11*
TiotropiumSpiriva HandihalerSpiriva Respimat
DPIMDI
$574*$574*
$19*$19*
Umeclidinium Incruse Ellipta DPI $386* $12*
Glycopyrrolate Seebri Neohaler DPI $474* $16*
Glycopyrrolate Lonhala Magnair Nebulizer - $48*
Revefenacin Yupelri Nebulizer - $45*
End in -ium
Reference: Lexicomp
*Brand Name only, no generic available
Inhaled Corticosteroids Not in Combination
Generic Name Brand Name(s) Dosage Form
Cost (AWP)One inhaler Per day
Inhaled Corticosteroids (ICSs)
Beclomethasone Qvar MDI $375* $13*
Budesonide Pulmicort Flexhaler DPI $308* $10*
Ciclesonide Alvesco MDI $329* $11*
Fluticasone Flovent HFA MDI $495* $17*
Fluticasone ArmonAir Digihaler MDI $359* $12*
Fluticasone Flovent Diskus DPI $398* $13*
Fluticasone Arnuity Ellipta DPI $296* $10*
Mometasone Asmanex Twisthaler DPI $270* $9*
Budesonide Pulmicort Respules Nebulizer - $22
Oral Prednisone 10mg daily - $0.55 per day
End in -sone or -nide
Reference: Lexicomp
*Brand Name only, no generic available
Are Inhaled Corticosteroids Helpful?
• The use of inhaled corticosteroids (ICS) in COPD is controversial.
• Routine use of ICS has been associated with an increased risk of pneumonia, thrush, dysphonia and reduction in bone density.
• ICS are also expensive medications that has been shown to have a minimal impact on COPD exacerbations.
• In a Cochrane Database Systematic Review, the risk of COPD exacerbations have only been reduced by one exacerbation per patient every four years for patients who were taking an ICS compared to salmeterol alone.
Nannini, Laserson, Poole. Combined corticosteroid and long-acting beta-2 agonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2012;(9):CD006829.
Does Discontinuing the Corticosteroid Worsen Exacerbations?
• In the WISDOM (Withdrawal of Inhaled Glucocorticoids and Exacerbations of COPD) trial, published in the NEJM 2014, ICS were withdrawn from patients who were receiving both a long-acting beta agonists and a long-acting muscarinic antagonists over a period of 12 weeks.
• These patients did not experience an increase in exacerbation or worsening of their condition over the 52 week study period with the withdrawal of ICS.
The study authors recommended discontinuation of ICS for patients with severe or very severe COPD.
Magnussen, Disse, Rodriguea-Roisin, et al. Withdrawal of inhaled glucocorticoids and exacerbations of COPD. N. Engl. J. Med. 2014;371:1285-4.
If the Patient Has an Exacerbation, How Many Days of Prednisone Should be Used?
• The REDUCE study, published in JAMA 2013, demonstrated that a short 5-day course of oral prednisone 40mg to manage acute COPD exacerbations was noninferior to a 14 day course.
• Time to next COPD exacerbation in patients with very severe COPD (GOLD stage IV disease) – 5 day steroid group = 43.5 days – 14 day steroid group = 29 days
Therefore, a short 5-day course with taper of oral prednisone 40mg/day would be appropriate for acute COPD exacerbations
compared to a 14 day course.
Leuppi JD, Schuetz P, Bingisser R, et al. Short-term vs conventional glucocorticoid therapy in acute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinical trial. JAMA. 2013;309:2223-2231.
Combination Inhaled MedicationsGeneric Name Dosage
Form Brand Name(s)Cost (AWP)
One inhaler Per day
SAMA/SABA Combination
Ipratropium/albuterol MDI Combivent $532* $18*
Ipratropium/albuterol Nebulizer DuoNeb - $9
LAMA/LABA Combinations
Umeclidinium/vilanterol DPI Anoro Ellipta $537* $18*
Tiotropium/olodaterol DPI Stiolto Respimat $206* $7*
Glycopyrrolate/indacaterol DPI Utibron Neohaler $440* $15*
Glycopyrrolate/formoterol DPI Bevespi Aerosphere $474* $16*
ICS/LABA Combinations
Budesonide/formoterol DPI Symbicort $403 $13
Fluticasone/salmeterolMDIDPIDPI
Advair HFAAdvair DiskusWixela Inhub
$584*$449$449
$19*$15$15
Fluticasone/vilanterol DPI Breo Ellipta $369* $12*
Mometasone/formoterol MDI Dulera $374* $12*
ICS/LAMA/LABA Combinations
Fluticasone/Umeclidinium/Vilanterol DPI Trelegy Ellipta $721* $24*
Budesonide/Glycopyrrolate/Formoterol MDI Breztri Aerosphere $708* $24*
Reference: Lexicomp
*Brand Name only, no generic available
Approach to a Patient’s Inhaled Medications
1) Separate the PRN orders from Routine ordersa) For PRN therapy, the patient should only be on a regimen that
contains one beta 2 agonist and/or one muscarinic antagonist.
b) For Routine therapy, the patient does not have to have something from all 3 categories, but if they are on something, they should only have one of that type of medication on board.
2) See if there are any duplicate therapies
3) Discontinue any duplicate therapies
4) Are there any medications you can consolidate?
Corticosteroids and long-acting beta 2 agonists and muscarinic antagonists should NOT be used on a PRN basis.
Patient Case• Terminal diagnosis – CHF and COPD
• Medications– Ventolin HFA (albuterol) – 2 puffs q4-6 hours PRN– Symbicort (Budesonide/formoterol) – 1 inhalation BID– Levothyroxine – 75mcg tab daily– Ipratropium neb – 1 vial via neb four times a day– Losartan – 25mg tab daily– Lorazepam – 0.5mg q4 hours PRN– Duoneb (albuterol/ipratropium) – 3mL vial via neb q4-6 hours PRN– Risperidone – 0.5mg BID
Patient Case – Step 1
• Ventolin HFA (albuterol) – 2 puffs q4-6 hours PRN• Symbicort (budesonide/formoterol)– 1 inhalation BID• Ipratropium neb – 1 vial via neb four times a day• Duoneb (albuterol/ipratropium) – 3mL vial via neb q4-6 hours PRN
Separate PRN orders from Routine orders
Patient Case – Step 1
• PRN– Ventolin HFA (albuterol) – 2 puffs q4-6 hours PRN– Duoneb (albuterol/ipratropium) – 3mL vial via neb q4-6 hours
PRN
• Routine– Ipratropium neb – 1 vial via neb four times a day– Symbicort (budesonide/formoterol) – 1 inhalation BID
Separate PRN orders from Routine orders
Patient Case – Step 2
• PRN– Ventolin HFA (albuterol) – 2 puffs q4-6 hours PRN– Duoneb (albuterol/ipratropium) – 3mL vial via neb q4-6 hours
PRN
• Routine– Ipratropium neb – 1 vial via neb four times a day– Symbicort (budesonide/formoterol) – 1 inhalation BID
See if there are any duplicate therapies
Patient Case – Step 2
Dosage Form Corticosteroids Beta 2 Agonists Muscarinic
Antagonists
PRN
Handheld Inhaler
Nebulizer
Routine
Handheld Inhaler
Nebulizer
OralPRN Albuterol / Ipratropium(Duoneb)
Albuterol HFA (Ventolin)
Patient Case – Step 2
Dosage Form Corticosteroids Beta 2 Agonists Muscarinic
Antagonists
PRN
Handheld Inhaler Albuterol HFA (Ventolin)
Nebulizer
Routine
Handheld Inhaler
Nebulizer
Oral
Ipratropium nebRoutineBudesonide / Formoterol
(Symbicort)
Albuterol / Ipratropium(DuoNeb)
Patient Case – Step 2
Dosage Form Corticosteroids Beta 2 Agonists Muscarinic
Antagonists
PRN
Handheld Inhaler Albuterol HFA (Proair)
Nebulizer
Routine
Handheld Inhaler
Nebulizer Ipratropium neb
Albuterol / Ipratropium(DuoNeb)
Budesonide / Formoterol(Symbicort)
Do you see the duplicate therapies?
Patient Case – Step 3
Dosage Form Corticosteroids Beta 2 Agonists Muscarinic
Antagonists
PRN
Handheld Inhaler Albuterol HFA (Proair)
Nebulizer
Routine
Handheld Inhaler
Nebulizer Ipratropium neb
Albuterol / Ipratropium(DuoNeb)
Discontinue any duplicate therapies
Budesonide / Formoterol(Symbicort)
Patient Case – Step 3
Dosage Form Corticosteroids Beta 2 Agonists Muscarinic
Antagonists
PRN
Handheld Inhaler Albuterol HFA (Proair)
Nebulizer
Routine
Handheld Inhaler
Nebulizer Ipratropium neb
Albuterol / Ipratropium(DuoNeb)
Discontinue any duplicate therapies
Budesonide / Formoterol(Symbicort)
Patient Case – Step 4
Dosage Form Corticosteroids Beta 2 Agonists Muscarinic
Antagonists
PRN Nebulizer
Routine
Handheld Inhaler
Nebulizer Ipratropium neb
Albuterol / Ipratropium(DuoNeb)
Is there any medications you can consolidate?
Budesonide / Formoterol(Symbicort)
Patient Case – Step 4
Dosage Form Corticosteroids Beta 2 Agonists Muscarinic
Antagonists
PRN Nebulizer
Routine
Handheld Inhaler
Nebulizer Ipratropium neb
Albuterol / Ipratropium(DuoNeb)
• Patients with end stage COPD generally do not have enough positive inhalation force to use handheld inhalers.
• The patient is already on nebulized solutions.
• Plan- D/C Symbicort and Ipratropium neb- Use Duoneb routinely and PRN- Add oral Prednisone, if a steroid is necessary
- Note: the patient has heart failure, steroid may cause fluid retention/edema
Budesonide / Formoterol(Symbicort)
Daliresp
• Daliresp is indicated to prevent COPD exacerbations but does not actually treat any symptoms or help the patient breath better.
• The time needed to see a benefit from Daliresp may exceed the life expectancy of the patient.
• The number of patients needed to treat (NNT) with Daliresp to prevent one moderate exacerbation per year was 5.– In other words if you treated 5 patients with Daliresp for 1 year then on
average only one exacerbation would be prevented.
• Evaluate the benefit versus the risk of side effects such as nausea, diarrhea and weight loss and consider discontinuing Daliresp.
AstraZeneca: Daliresp Efficacy. Data on File, REF-25736, AZPLP. https://www.daliresphcp.com/daliresp-efficacy.html
Theophylline
• Has a narrow therapeutic window and requires blood draws to determine blood concentration levels.
• As renal function declines watch for signs and symptoms of toxicity for Theophylline.
• Most common symptoms are gastrointestinal: increased appetite, thirst, nausea and vomiting (possibly with blood)
• Review to lower dose or increase dosing interval as renal and liver functions decline or discontinue
Reference: Lexicomp
Singulair (Montelukast)
• Montelukast (Singulair) is indicated for the treatment of allergic rhinitis and asthma, not COPD.
• The FDA placed a safety alert concerning the risk of neuropsychiatric events (serious behavior and mood-related changes) with this medication.
• Please consider OTC products for allergic rhinitis or nebs for asthma as the safest alternative or discontinuing the medication.
Reference: Lexicomp
Patient and Caregiver Talking Points
• Recognize that discussion on replacing inhalers may be interpreted by patients/families that the provider is “giving up”, abandoning the patient, and might suggest that death is imminent.– Provide reassurance that health care team is not “giving up” on
the patient
• Use positive language and offer options
• A shared decision-making approach may increase chances of successful deprescribing or conversation to more appropriate medications.
Reference: NHPCO. Hospice Medication Deprescribing Toolkit. November 2020, Version 1.0
Talking Point Examples• “Can you show me how you are using your inhaler? It’s ok if you don’t remember, we can
review the steps together.”
• “It seems you are having some difficulty using your inhalers. As your disease progresses it may be useful to make some adjustments to your medications. What worked before may not work as well for you now. Would you like to talk about making your medication routine a little less complicated?”
• “There are other medications for shortness of breath/anxiety that may be more effective than your current inhaler.”
• “It sounds like it’s hard for you to make a decision about stopping your inhaler. Can I share what my experiences and observations have been?”
• “We really just want your breathing to be more comfortable. I want you to know this is a team effort and you’re in charge of the team. I appreciate you allowing me to talk with you today.”
• “Before I visit next week, I’ll give your doctor an update and get her input. She might suggest stopping the inhalers and using a nebulizer. Are you willing to give it a try?”
• To the prescriber: “I have observed the patient who is unable to properly use the inhalers anymore. I believe switching to a less complicated delivery system may greatly improve her outcomes. Are you ok with me making this change?”
Reference: NHPCO. Hospice Medication Deprescribing Toolkit. November 2020, Version 1.0
Management of Dyspnea
Step 1: Non-pharmacological interventions
• Elevate the head of the bed
• Use a fan to move cool air over the patient‒ Open a window if possible
• Eliminate environmental irritants
• Give reassurance during acute distress
• If feasible, teach the patient breathing exercises and relaxation techniques
• Mouth breathing and supplemental oxygen will dry out the mouth. Maintain adequate humidity in the room and provide good oral hygiene
Management of Dyspnea
Step 2: Optimize current inhaled therapy
• Optimize Oxygen treatment
• Optimize nebulized inhaled medications‒ Discontinue duplicate therapies‒ Replace handheld inhalers with nebulized treatment
Management of Dyspnea
Step 3: Addition of an opioid to reduce respiratory rate
Morphine (MSIR, Roxanol)5 – 10mg PO/SL q1 hour PRN
OR
Oxycodone (OxyIR, OxyFast)2.5 – 7.5mg PO/SL q1 hour PRN
Titrate to effect and monitor respiratory rate
Management of Dyspnea
Step 4: Addition of a benzodiazepine to reduce anxiety
Lorazepam0.5 – 2mg PO/SL/IV q4 hours PRN
Summary• Approach to a patient’s inhaled medications
1) Separate PRN orders from Routine orders2) See if there are any duplicate therapies3) Discontinue any duplicate therapies4) Are there any medications you can consolidate?
• Duoneb (routinely and prn), plus Prednisone (if a steroid medication is needed) is the most cost-effective therapy for hospice patients with a terminal diagnosis of COPD or lung cancer.
• Inhaled corticosteroids should be discontinued in patients with severe or very severe COPD.
• A short 5-day course with a taper of oral Prednisone 40mg/day would be appropriate for acute COPD exacerbations.
• Management of dyspnea1) Non-pharmacological interventions2) Optimize current inhaled therapy3) Addition of an opioid to reduce respiratory rate4) Addition of a benzodiazepine to reduce anxiety
Questions?