inhaled respiratory medications: how to simplify inhaled

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


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


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


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


• 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


• 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


Dosage Form Corticosteroids Beta 2 Agonists Muscarinic

Antagonists

PRN

Handheld Inhaler

Nebulizer

Routine

Handheld Inhaler

Nebulizer

OralPRN Albuterol / Ipratropium(Duoneb)

Albuterol HFA (Ventolin)



Antagonists

PRN

Handheld Inhaler Albuterol HFA (Ventolin)

Nebulizer

Routine

Handheld Inhaler

Nebulizer

Oral

Ipratropium nebRoutineBudesonide / Formoterol

(Symbicort)

Albuterol / Ipratropium(DuoNeb)



Antagonists

PRN

Handheld Inhaler Albuterol HFA (Proair)

Nebulizer

Routine

Handheld Inhaler

Nebulizer Ipratropium neb


Budesonide / Formoterol(Symbicort)

Do you see the duplicate therapies?



Antagonists

PRN

Handheld Inhaler Albuterol HFA (Proair)

Nebulizer

Routine

Handheld Inhaler



Discontinue any duplicate therapies




Antagonists

PRN Nebulizer

Routine

Handheld Inhaler



Is there any medications you can consolidate?




Antagonists

PRN Nebulizer

Routine

Handheld Inhaler



• 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


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.


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?”


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


Step 2: Optimize current inhaled therapy

• Optimize Oxygen treatment

• Optimize nebulized inhaled medications‒ Discontinue duplicate therapies‒ Replace handheld inhalers with nebulized treatment


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


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?

inhaled respiratory medications: how to simplify inhaled

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