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A Visual Approach to SimplifyingRespiratory Drug RegimensStephanie Cheng, PharmD, MPH, BCGPInhaled Respiratory Drugs3 Main CategoriesBeta 2 Agonists Binds to beta-2 receptorsRelaxation of smooth muscles in the lungDilation and opening of airwaysMuscarinic Antagonists Inhibits acetylcholine in bronchial smooth muscleBronchodilationCan be mixedand matchedin variouscombinationsCorticosteroids Inhibits the inflammatory response1
Adverse Effects of Inhaled MedicationsDrug CategoryAdverse EffectsBeta 2 agonistsTachycardia (up to 200 beats/minute), arrhythmias,nervousness, headache, tremor, dry mouth,palpitation, nausea, dizziness, sleeplessness,hypertension or hypotensionMuscarinicantagonistsDizziness, headache, dry mouth, dyspepsia, nausea,UTI, urinary retention, constipationCorticosteroidsIncrease risk of upper respiratory tract infections,headache, pharyngitisDosage Forms Handheld Inhaler––––––Metered dose inhaler (MDI)Dry powder inhaler ld inhalers Require adequate inhalation force Require coordination to use Are generally more expensivecompared to the nebulized solution Nebulized solution Oral tablet (Albuterol tablet, corticosteroid: prednisone) Beta 2 agonists and muscarinic antagonists– Short-acting and long-acting formulations2
Respiratory Medications NOT in CombinationCorticosteroids Handheld Inhaler-End in-terolBeta 2 AgonistsEnd in-sone or -nide Handheld InhalerBeclomethasone (Qvar)Budesonide (Pulmicort Flexhaler)Ciclesonide (Alvesco)Fluticasone (Flovent HFA/Diskus)Mometasone (Asmanex Twisthaler)- Short Acting Albuterol HFA (Ventolin HFA, Proair HFA, Proventil HFA)Levalbuterol HFA (Xopenex HFA)- Long acting Nebulized solution- Budesonide (Pulmicort Respules) Oral – PrednisoneFormoterol (Foradil Aerolizer)Indacaterol (Arcapta Neohaler)Olodaterol (Striverdi Respimat)Salmeterol (Serevent Diskus) Nebulized solutionMuscarinic Antagonists Handheld Inhaler- Short ActingEnd in-ium - Long Acting- Short Acting Ipratropium HFA (Atrovent HFA)- Long Acting Albuterol (AccuNeb)Levalbuterol (Xopenex)Aclidinium (Turdorza Pressair)Tiotropium (Spiriva Handihaler/Respimat)Umeclidinium (Incruse Ellipta)Arformoterol (Brovana)Formoterol (Perforomist) Oral - AlbuterolNebulized solution - IpratropiumRespiratory Medications NOT in CombinationCorticosteroidsLong acting(Qvar)AlbuterolHFA(Foradil Aerolizer)Budesonide(Ventolin HFA,Proair HFA,Proventil HFA)IndacaterolBeclomethasone(Pulmicort Flexhaler)HandheldInhalerBeta 2 agonistsShort actingMuscarinic antagonistsShort ta Neohaler)IpratropiumHFA(Striverdi Respimat)CiclesonideOlodaterol(Alvesco)(Atrovent HFA)(MDI or DPI)Fluticasone (Flovent LevalbuterolHFAHFA, Flovent Diskus)Long actingTiotropium(SpirivaHandihaler,Spiriva Respimat)Salmeterol(Serevent Diskus)Umeclidinium(Xopenex HFA)(Incruse Ellipta)Mometasone(Asmanex rolBudesonide(AccuNeb)(Brovana)(Pulmicort st)PrednisoneIpratropiumAlbuterol3
Respiratory Medications in CombinationBeta 2 Agonist Muscarinic Antagonists Short Acting – PRN or Routine Use– Handheld Inhaler – Albuterol/Ipratropium (Combivent Respimat)– Nebulized solution – Albuterol/Ipratropium (DuoNeb) Long acting – Routine Use Only– Vilanterol/Umeclidinium (Anoro Ellipta)– Olodaterol/Tiotropium (Stiolto Respimat)Alllong-actinginhalers arehandheldinhalersCorticosteroid Beta 2 Agonist Long acting – Routine Use Only––––Budesonide/formoterol (Symbicort)Fluticasone/salmeterol (Advair HFA, Advair Diskus)Fluticasone/vilanterol (Breo Ellipta)Mometasone/formoterol (Dulera)Respiratory Medications in CombinationCorticosteroidsBeta 2 AgonistMuscarinic AntagonistsShort-Acting – PRN or Routine UseHandheldInhaler (MDI)Albuterol / IpratropiumNebulizedSolutionAlbuterol / Ipratropium(Combivent Respimat)(Duoneb)Long-Acting – Routine Use OnlyVilanterol / Umeclidinium(Anoro Ellipta)Olodaterol / Tiotropium(Stiolto Respimat)HandheldDevice(MDI or DPI)Budesonide / Formoterol(Symbicort)Fluticasone / Salmeterol(Advair HFA, Advair Diskus)Fluticasone / Vilanterol(Breo Ellipta)Mometasone / Formoterol(Dulera)4
Approach to a Patient’s Inhaled Medications1) Separate the PRN orders from Routine ordersa) For PRN therapy, the patient should only be on a regimen thatcontains one beta 2 agonist and/or one muscarinic antagonist.Corticosteroids and long acting beta 2 agonists andmuscarinic antagonists should NOT be used on a PRN basis.b) For Routine therapy, the patient does not have to havesomething 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 therapies3) Discontinue any duplicate therapies4) Are there any medications you can consolidate?Patient Case #1 Terminal Diagnosis – COPD Medication List––––––––Proair HFA (albuterol) – 2 puffs q4-6 hours PRNCombivent Respimat (albuterol/ipratropium) – 1 puff q4 hours PRNSpiriva Handihaler (tiotropium) – 1 cap inhaled once dailyXopenex (levalbuterol) – 3mL vial via neb four times a dayAdvair (fluticasone/salmeterol) – 1 inhalation BIDDuoneb (albuterol/ipratropium) – 3mL vial via neb four times a dayPrednisone 10mg PO dailyDuoneb (albuterol/ipratropium) – 3mL vial via neb q4-6 hours PRN5
Patient Case #1 – Step 1Separate PRN orders from Routine orders Proair HFA (albuterol) – 2 puffs q4-6 hours PRNCombivent Respimat (albuterol/ipratropium) – 1 puff q4 hours PRNSpiriva Handihaler (tiotropium) – 1 cap inhaled once dailyXopenex (levalbuterol) – 3mL vial via neb four times a dayAdvair (fluticasone/salmeterol) – 1 inhalation BIDDuoneb (albuterol/ipratropium) – 3mL vial via neb four times a dayPrednisone 10mg PO dailyDuoneb (albuterol/ipratropium) – 3mL vial via neb q4-6 hours PRNPatient Case #1 – Step 1Separate PRN orders from Routine ordersPRN orders Proair HFA (albuterol) – 2 puffs q4-6 hours PRN Combivent Respimat (albuterol/ipratropium) – 1 puff q4 hours PRN Duoneb (albuterol/ipratropium) – 3mL vial via neb q4-6 hours PRNRoutine orders Spiriva Handihaler (tiotropium) – 1 cap inhaled once daily Xopenex (levalbuterol) – 3mL vial via neb four times a day Advair (fluticasone/salmeterol) – 1 inhalation BID Duoneb (albuterol/ipratropium) – 3mL vial via neb four times a day Prednisone 10mg PO daily6
Patient Case #1 – Step 2See if there are any duplicate therapiesPRN orders Proair HFA (albuterol) – 2 puffs q4-6 hours PRN Combivent Respimat (albuterol/ipratropium) – 1 puff q4 hours PRN Duoneb (albuterol/ipratropium) – 3mL vial via neb q4-6 hours PRNRoutine orders Spiriva Handihaler (tiotropium) – 1 cap inhaled once daily Xopenex (levalbuterol) – 3mL vial via neb four times a day Advair (fluticasone/salmeterol) – 1 inhalation BID Duoneb (albuterol/ipratropium) – 3mL vial via neb four times a day Prednisone 10mg PO dailyDuplicate Inhaled Therapy TemplateDosageFormPRNCorticosteroidsBeta 2 zerHandheldInhalerRoutineNebulizerOral7
Patient Case #1 – Step 2DosageFormPRNCorticosteroidsBeta 2 zerHandheldInhalerRoutineNebulizerOralAlbuterol HFA (Proair)PRNAlbuterol / Ipratropium(Combivent Respimat)Albuterol / Ipratropium(Duoneb)Patient Case #1 – Step 2DosageFormPRNCorticosteroidsBeta 2 AgonistsMuscarinicAntagonistsAlbuterol HFA (Proair)HandheldInhalerAlbuterol / Ipratropium(Combivent Respimat)Albuterol / NebulizerOralTiotropium (Spiriva)RoutineLevalbuterol neb(Xopenex)PrednisoneFluticasone / Salmeterol(Advair)Albuterol / Ipratropium(Duoneb)8
Patient Case #1 – Step 2DosageFormPRNCorticosteroidsBeta 2 AgonistsMuscarinicAntagonistsAlbuterol HFA (Proair)HandheldInhalerAlbuterol / Ipratropium(Combivent Respimat)Albuterol / Ipratropium(DuoNeb)NebulizerTiotropium (Spiriva)HandheldInhalerLevalbuterol neb (Xopenex)Fluticasone / Salmeterol(Advair)RoutineAlbuterol / Ipratropium(DuoNeb)NebulizerOralPrednisonePatient Case #1 – Step 2DosageFormPRNCorticosteroidsBeta 2 AgonistsMuscarinicAntagonistsAlbuterol HFA (Proair)HandheldInhalerAlbuterol / Ipratropium(Combivent Respimat)Albuterol / Ipratropium(DuoNeb)NebulizerTiotropium (Spiriva)HandheldInhalerLevalbuterol neb (Xopenex)Fluticasone / Salmeterol(Advair)RoutineAlbuterol / Ipratropium(DuoNeb)NebulizerOralPrednisoneDo you see the duplicate therapies?9
Patient Case #1 - Step 3Discontinue any duplicate therapies Determine the severity of the patient’s COPD or lung condition. If they are taking nebulized inhaled medications, they most likely do nothave 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 lungcancer generally do not have enough positive inhalation force touse handheld devices and should be on nebulized therapy.Step 3 Discontinue any duplicate agonistsBeta 2 AgonistsAlbuterol HFA (Proair)HandheldInhalerAlbuterol / Ipratropium(Combivent Respimat)Albuterol / Ipratropium(DuoNeb)NebulizerTiotropium (Spiriva)HandheldInhalerLevalbuterol neb (Xopenex)Fluticasone / Salmeterol(Advair)RoutineAlbuterol / Ipratropium(DuoNeb)NebulizerOralPrednisoneWhich medications would you discontinue?10
Step 3 Discontinue any duplicate agonistsBeta 2 AgonistsAlbuterol HFA (Proair)HandheldInhalerAlbuterol / Ipratropium(Combivent Respimat)Albuterol / Ipratropium(DuoNeb)NebulizerTiotropium (Spiriva)HandheldInhalerLevalbuterol neb (Xopenex)Fluticasone / Salmeterol(Advair)RoutineAlbuterol / Ipratropium(DuoNeb)NebulizerOralPrednisoneThe combination therapy of using DuoNeb routinely and PRN, plus prednisone (if asteroid medication is needed) is the most cost-effective therapy for hospice patientswith a terminal diagnosis of COPD or lung cancer.Step 4 Consolidating MedicationsDosageFormPRNCorticosteroidsBeta 2 AgonistsMuscarinicAntagonistsNebulizerAlbuterol / Ipratropium(DuoNeb)NebulizerAlbuterol / Ipratropium(DuoNeb)RoutineOralPrednisoneAre there any medications you can consolidate?11
Patient Case #2 Terminal diagnosis – CHF and COPD Medications––––––––––Ventolin HFA (albuterol) – 2 puffs q4-6 hours PRNLasix (furosemide) – 20mg tab BIDPotassium chloride – 20mEq tab BIDAdvair (fluticasone/salmeterol) – 1 inhalation BIDLevothyroxine – 75mcg tab dailyIpratropium neb – 1 vial via neb four times a dayLisinopril – 10mg tab dailyLorazepam – 1mg q4 hours PRNDuoneb (albuterol/ipratropium) – 3mL vial via neb q4-6 hours PRNHaloperidol – 1mg BIDPatient Case #2 – Step 1Separate PRN orders from Routine orders Ventolin HFA (albuterol) – 2 puffs q4-6 hours PRNAdvair (fluticasone/salmeterol) – 1 inhalation BIDIpratropium neb – 1 vial via neb four times a dayDuoneb (albuterol/ipratropium) – 3mL vial via neb q4-6 hours PRN12
Patient Case #2 – Step 1Separate PRN orders from Routine orders PRN– Ventolin HFA (albuterol) – 2 puffs q4-6 hours PRN– Duoneb (albuterol/ipratropium) – 3mL vial via neb q4-6 hoursPRN Routine– Ipratropium neb – 1 vial via neb four times a day– Advair (fluticasone/salmeterol) – 1 inhalation BIDPatient Case #2 – Step 2See if there are any duplicate therapies PRN– Ventolin HFA (albuterol) – 2 puffs q4-6 hours PRN– Duoneb (albuterol/ipratropium) – 3mL vial via neb q4-6 hoursPRN Routine– Ipratropium neb – 1 vial via neb four times a day– Advair (fluticasone/salmeterol) – 1 inhalation BID13
Patient Case #2 – Step 2DosageFormPRNCorticosteroidsBeta 2 zerHandheldInhalerRoutineNebulizerPRNAlbuterol HFA (Ventolin)OralAlbuterol / Ipratropium(Duoneb)Patient Case #2 – Step 2DosageFormPRNCorticosteroidsHandheldInhalerBeta 2 AgonistsMuscarinicAntagonistsAlbuterol HFA (Ventolin)Albuterol / NebulizerOralRoutineIpratropium nebFluticasone / Salmeterol(Advair)14
Patient Case #2 – Step rol HFA (Proair)Albuterol / MuscarinicAntagonistsBeta 2 AgonistsFluticasone / Salmeterol(Advair)NebulizerIpratropium nebDo you see the duplicate therapies?Patient Case #2 – Step rol HFA (Proair)Albuterol / NebulizerMuscarinicAntagonistsBeta 2 AgonistsFluticasone / Salmeterol(Advair)Ipratropium nebDiscontinue any duplicate therapies15
Patient Case #2 – Step rol HFA (Proair)Albuterol / MuscarinicAntagonistsBeta 2 AgonistsFluticasone / Salmeterol(Advair)NebulizerIpratropium nebDiscontinue any duplicate therapiesPatient Case #2 – Step 4DosageFormPRNRoutineCorticosteroidsBeta 2 AgonistsAlbuterol / erMuscarinicAntagonistsFluticasone / Salmeterol(Advair)Ipratropium nebIs there any medications you can consolidate?16
Patient Case #2 – Step 4DosageFormPRNCorticosteroidsBeta 2 AgonistsAlbuterol / Fluticasone / Salmeterol(Advair)Nebulizer MuscarinicAntagonistsIpratropium nebPatients with end stage COPD generally do not have enoughpositive inhalation force to use handheld inhalers.The patient is already on nebulized solutions.Plan-D/C Advair and Ipratropium nebUse Duoneb routinely and PRNAdd oral Prednisone, if a steroid is necessaryNote regarding inhaled corticosteroids use in COPD The use of inhaled corticosteroids (ICS) in COPD is controversial. Routine use of ICS has been associated with an increased risk ofpneumonia, thrush, dysphonia and reduction in bone density. ICS are also expensive medications that has been shown to have aminimal impact on COPD exacerbations. In a Cochrane Database Systematic Review, the risk of COPDexacerbations have only been reduced by one exacerbation perpatient every four years for patients who were taking an ICScompared to salmeterol alone.Nannini, Laserson, Poole. Combined corticosteroid and long-acting beta-2 agonists for chronicobstructive pulmonary disease. Cochrane Database Syst Rev 2012;(9):CD006829.17
Note regarding inhaled corticosteroids use in COPD In the WISDOM (Withdrawal of Inhaled Glucocorticoids andExacerbations of COPD) trial, published in the NEJM 2014, ICS werewithdrawn from patients who were receiving both a long-acting betaagonists and a long-acting muscarinic antagonists over a period of 12weeks. These patients did not experience an increase in exacerbation orworsening of their condition over the 52 week study period withthe withdrawal of ICS.The study authors recommended discontinuation of ICS forpatients with severe or very severe COPD.Magnussen, Disse, Rodriguea-Roisin, et al. Withdrawal of inhaled glucocorticoids andexacerbations of COPD. N. Engl. J. Med. 2014;371:1285-4.Note regarding inhaled corticosteroids use in COPD The REDUCE study, published in JAMA 2013, demonstrated that ashort 5-day course of oral prednisone 40mg to manage acute COPDexacerbations was noninferior to a 14 day course. Time to next COPD exacerbation in patients with very severeCOPD (GOLD stage IV disease)– 5 day steroid group 43.5 days– 14 day steroid group 29 daysTherefore, a short 5-day course of oral prednisone 40mg/daywould be appropriate for acute COPD exacerbations.Leuppi JD, Schuetz P, Bingisser R, et al. Short-term vs conventional glucocorticoid therapy inacute exacerbations of chronic obstructive pulmonary disease: the REDUCE randomized clinicaltrial. JAMA. 2013;309:2223-2231.18
Summary Approach to a patient’s inhaled medications1)2)3)Separate PRN orders from Routine ordersSee if there are any duplicate therapiesDiscontinue any duplicate therapies Duoneb (routinely and prn), plus Prednisone (if a steroid medicationis needed) is the most cost-effective therapy for hospice patients with aterminal diagnosis of COPD or lung cancer. Inhaled corticosteroids should be discontinued in patients withsevere or very severe COPD. A short 5-day course of oral Prednisone 40mg/day would beappropriate for acute COPD exacerbations.Conclusion By identifying and discontinuing duplicate inhaledrespiratory therapies, patients would be able to avoidpotential toxicity and adverse effects. This also helps hospices reduce costs towards morecost-effective medications19
Questions?Stephanie Cheng, PharmD, MPH, BCGPClinical PharmacistHospice Pharmacy Solutionsscheng@hospicepharmacysolutions.com20
(Breo Ellipta) Mometasone / Formoterol (Dulera) 5 Approach to a Patient's Inhaled Medications 1) Separate the PRN orders from Routine orders a) For PRN therapy, the patient should only be on a regimen that contains one beta 2 agonist and/or one muscarinic antagonist.
