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Challenges of Challenges of Pharmacotherapy in the Pharmacotherapy in the
Treatment of Cystic FibrosisTreatment of Cystic Fibrosis
Hanna Phan, Pharm.D. Hanna Phan, Pharm.D. Clinical Assistant ProfessorClinical Assistant Professor
Clinical Pharmacy Specialist, Pediatric Pulmonary MedicineClinical Pharmacy Specialist, Pediatric Pulmonary Medicine
Residency Program Director, Pediatric Pharmacotherapy Residency Program Director, Pediatric Pharmacotherapy Department of Pharmacy Practice and ScienceDepartment of Pharmacy Practice and Science
The University of Arizona - College of PharmacyThe University of Arizona - College of Pharmacy
ObjectivesObjectives
• Review common medications Review common medications used in the used in the outpatient and inpatient settings in the outpatient and inpatient settings in the treatment of cystic fibrosis (CF)treatment of cystic fibrosis (CF)
• Identify challenges Identify challenges of treatment adherence of treatment adherence in CFin CF
• Understand the Understand the role of a clinical role of a clinical pharmacist pharmacist as part of an as part of an interdisciplinaryinterdisciplinary team in management of CFteam in management of CF
**Conflict of Interest: I have no relevant financial relationships to disclose for this presentation.
Disease Severity, Age, and TherapyDisease Severity, Age, and Therapy
SA, 2 yo ♀ EN, 7 yo ♀ CM, 30 yo ♂ JS, 50 yo ♂
CPTCreon 12,000AlbuterolAquADEK liquid
CPTCreon 12,000AlbuterolSource CFDornase alfaTobramycinFluticasone NSBudesonide
CPTCreon 24,000AlbuterolSource CFDornase alfaTobramycinAzithromycinPantoprazoleNaCl 7% SolutionDronabinolMegestrolUrsodiolFluticasone NSFluticasone/salmeterolZolpidem
CPTUltrase MT 20Albuterol Source CFVitamin DDornase alfaTobramycinAzithromycinPantoprazoleInsulin lisproInsulin lantusClonazepamFluticasone/salmeterolHydrochlorothiazideFluticasone NSMontelukastDocusate sodiumCPT = Chest physical therapy
CF Drug Therapy BasicsCF Drug Therapy Basics• Therapy selection Therapy selection depends on depends on CF severity CF severity
and and organ systems affectedorgan systems affected– Pulmonary, infectious diseases, etc.Pulmonary, infectious diseases, etc.– Gastrointestinal, hepatic, etc.Gastrointestinal, hepatic, etc.
• Different pharmacokinetics Different pharmacokinetics with CFwith CF– Drug selection, dosing, frequency, adverse Drug selection, dosing, frequency, adverse
effectseffects
• Off-label Off-label medication usemedication use
• ‘‘Polypharmacy’ Polypharmacy’ is a common concernis a common concern
Pharmacokinetic Challenges Pharmacokinetic Challenges in CFin CF
• AbsorptionAbsorption – Differences in gastric pHDifferences in gastric pH– Slower GI motilitySlower GI motility
• DistributionDistribution– Larger volume of distributionLarger volume of distribution
• MetabolismMetabolism– Possible difference in hepatic clearancePossible difference in hepatic clearance
• EliminationElimination– Increased renal clearanceIncreased renal clearance
Overall Goals of TherapyOverall Goals of Therapy Prolong survivalProlong survival
Optimize/improve quality of lifeOptimize/improve quality of life
Slow disease progressionSlow disease progression
Achieve normal growth and developmentAchieve normal growth and development
Decrease hospitalization frequencies and durationDecrease hospitalization frequencies and duration
Minimize adverse drug reactionsMinimize adverse drug reactions
Pulmonary Drug TherapyPulmonary Drug Therapy
Bronchodilators – Bronchodilators – ββ agonists agonists11
• Nebulized or HFA inhalerNebulized or HFA inhaler• Commonly used as part of Commonly used as part of
CPT CPT – Bronchial hyperresponsiveness, Bronchial hyperresponsiveness,
wheezingwheezing– Prevent bronchospasm during Prevent bronchospasm during
respiratory therapy and other respiratory therapy and other inhaled treatmentsinhaled treatments
• AlbuterolAlbuterol– 2.5mg nebulized BID (w/ CPT), 2.5mg nebulized BID (w/ CPT),
increased during exacerbation an/or increased during exacerbation an/or hospitalizationhospitalization
• LevalbuterolLevalbuterol– When to use versus albuterol?When to use versus albuterol?– Why is it not used for everyone?Why is it not used for everyone?
Images, accessed 11/15/09:http://peacehealthsleepcenter.org/kbase/media/medical/multum/proairhfa.jpg
http://www.healthsquare.com/common/images/d/DEY06971_86649_5.JPG
Dornase alfa (Pulmozyme®)Dornase alfa (Pulmozyme®)1,21,2
• Recombinant DNA enzymeRecombinant DNA enzyme• Selectively cleaves Selectively cleaves
extracellular DNA from extracellular DNA from pulmonary secretions, pulmonary secretions, improve viscoelastic improve viscoelastic properties of secretionsproperties of secretions– Promotes airway clearance of Promotes airway clearance of
mucous mucous reduce respiratory reduce respiratory infection riskinfection risk
– ↓ ↓ Hospital LOS, duration of IV Hospital LOS, duration of IV antibioticsantibiotics
• Given as part of CPT Given as part of CPT regimenregimen
Image, accessed 11/15/09:http://www.biology.iupui.edu/biocourses/Biol540/images/3pulmozyme.jpg
Hypertonic SalineHypertonic Saline1,3,41,3,4 • Increases hydration of airway Increases hydration of airway
surface liquid via osmotic flowsurface liquid via osmotic flow– Breaks ionic bonds in mucusBreaks ionic bonds in mucus– Stimulates cilial beat via the Stimulates cilial beat via the
release of prostaglandin E2release of prostaglandin E2– Helps improve mucociliary Helps improve mucociliary
clearanceclearance– Causes sputum production and Causes sputum production and
cough cough improve airway improve airway obstructionobstruction
• Should precede dose with Should precede dose with bronchodilator (i.e., albuterol) to bronchodilator (i.e., albuterol) to decrease incidence of decrease incidence of bronchospasm, part of CPTbronchospasm, part of CPT
• 3% (3.5%) and 7% solutions3% (3.5%) and 7% solutions
Image, accessed 11/15/09:http://www.pari.com/images/pixcontent/pdd/products/Hyper-Sal_Vile_Box_7_M.jpg
CorticosteroidsCorticosteroids• InhaledInhaled
– Budesonide (Pulmicort®), Fluticasone Budesonide (Pulmicort®), Fluticasone (Flovent ®)(Flovent ®)
– Attenuate reactive airways, reduce Attenuate reactive airways, reduce inflammationinflammation
– Concurrent asthmaConcurrent asthma
• Systemic (oral)Systemic (oral)– PrednisonePrednisone– Reduce inflammation (?) Reduce inflammation (?)
Image, accessed 11/15/09:http://www.floventdiskus.com/Flovent_HFA_pg.html
High-dose IbuprofenHigh-dose Ibuprofen1,51,5 • Inhibits the migration, adherence, Inhibits the migration, adherence,
swelling, and aggregation of swelling, and aggregation of neutrophils, as well as the release neutrophils, as well as the release of lysosomal enzymesof lysosomal enzymes– Decreases Decreases rate of declinerate of decline of FEV1, of FEV1,
decreases hospitalizationsdecreases hospitalizations– Study population…Study population…
• Requires pharmacokinetic dosing Requires pharmacokinetic dosing • ADE concerns: GI bleedingADE concerns: GI bleeding• Currently not used in all patientsCurrently not used in all patients
Image, accessed 11/21/09:http://patrickdowning.files.wordpress.com/2008/11/13_ibuprofen-pill.jpg
AzithromycinAzithromycin1,61,6
• ““Anti-inflammatory” Anti-inflammatory” agentagent– Immunomodulatory properties– Suppresses inflammation– Alters biofilm formation
• Not “antibiotic prophylaxis”Not “antibiotic prophylaxis”• Mon-Wed-FriMon-Wed-Fri regimen regimen• ConsiderationsConsiderations
– Check for presence of atypical Check for presence of atypical mycobacterium mycobacterium
– Patient weight Patient weight – Presence of Presence of mucoid P. mucoid P.
aeruginosa aeruginosa (but new data!)(but new data!)Image, accessed 11/21/09:
http://www.peacehealth.org/kbase/multum/d00091a1.htm
Antimicrobial TherapyAntimicrobial Therapy7,87,8
• Intravenous (IV), oral (PO), or nebulized Intravenous (IV), oral (PO), or nebulized (NMT) route(NMT) route– Treatment (mean duration ~ 14-21 days)Treatment (mean duration ~ 14-21 days)– Prophylaxis (outpatient, on/off months)Prophylaxis (outpatient, on/off months)
• Factors affecting antibiotic selectionFactors affecting antibiotic selection::Cultures and susceptibilities (past and Cultures and susceptibilities (past and
present)present)Often more than one pathogen…Often more than one pathogen…
AgeAgeChild vs. adolescent vs. adultChild vs. adolescent vs. adult
Organ function (i.e., renal, hepatic)Organ function (i.e., renal, hepatic)History of allergies and adverse drug eventsHistory of allergies and adverse drug events
7Gibson RL, Burns JL, Ramsey BW. Pathophysiology and management of pulmonary infections in cystic fibrosis. Am J Respir Crit Care Med. 2003 Oct 15;168(8):918-51.
9Cystic Fibrosis Foundation Patient Registry. 2001 Annual Data Report to the Center Directors. Bethesda, MD: Cystic Fibrosis Foundation; 2002.
P. aeruginosa
S. aureus
Antibiotics for CF ExacerbationAntibiotics for CF Exacerbation7,87,8
• Multi-drug resistant (MDR) Multi-drug resistant (MDR) pathogens are pathogens are commoncommon
• 2+ drug therapy approach2+ drug therapy approach– From different drug classesFrom different drug classes– OutpatientOutpatient
• Oral agent(s) + nebulized agent + increased CPTOral agent(s) + nebulized agent + increased CPT• IV agent(s) ± oral agent(s) ± nebulized agent + IV agent(s) ± oral agent(s) ± nebulized agent +
increased CPTincreased CPT
– InpatientInpatient• IV agent(s) ± oral agent(s) ± nebulized agent + IV agent(s) ± oral agent(s) ± nebulized agent +
increased CPTincreased CPT
Commonly Used Antibiotics in CF:Commonly Used Antibiotics in CF:Oral AgentsOral Agents7,87,8
• S. aureusS. aureus– Methicillin-susceptible (MSSA)Methicillin-susceptible (MSSA)
• Cephalexin, amoxicillin/clavulanateCephalexin, amoxicillin/clavulanate
– Methicillin-resistant (MRSA)Methicillin-resistant (MRSA)• Sulfamethoxazole/trimethoprim, clindamycin, Sulfamethoxazole/trimethoprim, clindamycin,
linezolidlinezolid
• P. aeruginosaP. aeruginosa– CiprofloxacinCiprofloxacin
• H. influenzaeH. influenzae– Amoxicillin/clavulanate, cefuroximeAmoxicillin/clavulanate, cefuroxime
Commonly Used Antibiotics in CF:Commonly Used Antibiotics in CF:Nebulized Agents Nebulized Agents 7,87,8
• P. aeruginosaP. aeruginosa– Tobramycin solution (TOBI®)Tobramycin solution (TOBI®)– Colistimethate (colistin)Colistimethate (colistin)
Commonly Used Antibiotics in CF: Commonly Used Antibiotics in CF: IV AgentsIV Agents7,87,8
Pathogen Antimicrobial
S. aureus Nafcillin (MSSA only)
Vancomycin
Linezolid
Clindamycin (watch for inducible resistance)
P. aeruginosa Piperacillin / tazobactam
Cefepime
Ciprofloxacin
Meropenem
An aminoglycoside - tobramycin or amikacin
Commonly Used Antibiotics in CF: Commonly Used Antibiotics in CF: IV AgentsIV Agents7,87,8
Pathogen Antimicrobial
S. maltophilia Sulfamethoxazole / trimethoprim
Piperacillin / tazobactam
Levofloxacin or moxifloxacin
Ticarcillin / Clavulanate + aztreonam
H. influenzaeAll drugs listed for P. aeruginosa provide coverage
(rec. 3rd gen cephalosporin), may not need for double coverage combination
Commonly Used Antibiotics in CF: Commonly Used Antibiotics in CF: IV AgentsIV Agents7,87,8
Pathogen Antimicrobial
B. cepaciaSulfamethoxazole / trimethoprim, meropenem, or
ciprofloxacin, may need multiple drug combination; known to be resistant to AGs
Nocardia
Sulfamethoxazole / trimethoprim, minocycline, or linezolid, multiple drug combinations usually not
necessary
Antifungal AgentsAntifungal Agents7,87,8
Pathogen Antifungal
Candida spp. (most) Fluconazole
Aspergillus spp. Itraconazole
Voriconazole
Scedosporium apiospermum Voriconazole
Antibiotic ProphylaxisAntibiotic Prophylaxis1,111,11
• Some patients may be given oral antibiotic Some patients may be given oral antibiotic therapy for prophylaxis (rare)therapy for prophylaxis (rare)
• Most common form is nebulized antibioticsMost common form is nebulized antibiotics– Tobramycin solution (TOBI®)Tobramycin solution (TOBI®)– Colistimethate (colistin)Colistimethate (colistin)
• The above are given twice a day, 28 days The above are given twice a day, 28 days on/off scheduleon/off schedule
Gastrointestinal and Nutritional Gastrointestinal and Nutritional Drug TherapyDrug Therapy
Concurrent GI/Nutrition IssuesConcurrent GI/Nutrition Issues
• Malabsorption (pancreatic insufficency)Malabsorption (pancreatic insufficency)
• Gastroesophageal reflux disease (GERD)Gastroesophageal reflux disease (GERD)
• GastroparesisGastroparesis
• Hepatobiliary diseaseHepatobiliary disease
• Distal intestinal obstruction syndrome Distal intestinal obstruction syndrome (DIOS)(DIOS)
• Poor intake/appetitePoor intake/appetite
• CF related diabetes (CFRD)CF related diabetes (CFRD)
Pancreatic InsufficiencyPancreatic Insufficiency12,1312,13
• Pancreatic enzyme replacement therapy Pancreatic enzyme replacement therapy (PERT)(PERT)
• Several manufacturers Several manufacturers – Creon®, Pancrease®, Pancrearb®, Ultrase®, Creon®, Pancrease®, Pancrearb®, Ultrase®,
Viokase®, ZenPep®, Pangestyme™Viokase®, ZenPep®, Pangestyme™
• FDA RulingFDA Ruling– All manufacturers of pancreatic enzyme All manufacturers of pancreatic enzyme
products products must secure FDA approval of their must secure FDA approval of their products by submitting New Drug Application products by submitting New Drug Application by 4/2009 by 4/2009 in order to remain available to in order to remain available to patientspatients
PERT ProductsPERT Products1414
Image, accessed 11/29/09: Up-to-date 2009 ©http://www.utdol.com/online/content/image.do;jsessionid=539B6F5A1A27621314B31A4EB12EB98C.1003?imageKey=PEDS%2F19219&view=print#
Pancreatic InsufficiencyPancreatic Insufficiency1212
• Nutritional supplementsNutritional supplements– Fat-soluble vitaminsFat-soluble vitamins
• Vitamins A, D, E, and KVitamins A, D, E, and K– ADEK®, AquADEK®, SourceCF®ADEK®, AquADEK®, SourceCF®
• Vitamin DVitamin D– ErgocalciferolErgocalciferol
• Vitamin EVitamin E– Over the counter supplement formulations (capsules)Over the counter supplement formulations (capsules)
– Iron supplementsIron supplements• Ferrous sulfate, ferrous gluconateFerrous sulfate, ferrous gluconate• Considerations with GERD medications…Considerations with GERD medications…
Gastroesophageal reflux Gastroesophageal reflux disease (GERD)disease (GERD)15,1615,16
• > 25-30% incidence > 25-30% incidence
• Histamine-2 receptor antagonists (H2RA)Histamine-2 receptor antagonists (H2RA)– FamotadineFamotadine– RanitidineRanitidine
• Proton pump inhibitors (PPI)Proton pump inhibitors (PPI)– Pantoprazole,lansoprazole,Pantoprazole,lansoprazole,
omeprazole, esomeprazoleomeprazole, esomeprazole– ““Enzyme Boosting”Enzyme Boosting”
Images, accessed 11/29/09: http://i45.photobucket.com/albums/f77/pharmerpillid/Prevacid15mgODT.jpg http://myhealth.ucsd.edu/library/healthguide/en-us/images/media/medical/Multum/protonix40mg.jpg
GastroparesisGastroparesis17,1817,18
• Often related to CFRDOften related to CFRD
• Affects the ability of the stomach to empty Affects the ability of the stomach to empty its contentsits contents– No blockage (obstruction)No blockage (obstruction)
• Drug therapy that Drug therapy that helps nausea/vomitinghelps nausea/vomiting– Ondansetron (Zofran®)Ondansetron (Zofran®)– Prochlorperazine (Compazine®)Prochlorperazine (Compazine®)
• Drug therapy can Drug therapy can help increase motilityhelp increase motility– Metoclopramide (Reglan®)Metoclopramide (Reglan®)– Erythromycin (E-Mycin®)Erythromycin (E-Mycin®)
Hepatobiliary DiseaseHepatobiliary Disease
• Up to 30% incidence, usually later in lifeUp to 30% incidence, usually later in life
• Bile duct obstruction from abnormal bile Bile duct obstruction from abnormal bile composition and flow (cholestasis)composition and flow (cholestasis)
• Potential complications: Potential complications: – CirrhosisCirrhosis– Biliary colic secondary to cholelithiasisBiliary colic secondary to cholelithiasis– Portal hypertension Portal hypertension liver transplant liver transplant
Hepatobiliary DiseaseHepatobiliary Disease19,2019,20
• Drug therapy: Drug therapy: UrsodiolUrsodiol– Ursodeoxycholic acidUrsodeoxycholic acid– 30 mg/kg/day BID (max 300 mg PO 30 mg/kg/day BID (max 300 mg PO
BID)BID)
• Clinical effectsClinical effects– Slows progression of disease, Slows progression of disease,
improves bile flowimproves bile flow– Displaces toxic bile acids and Displaces toxic bile acids and
reduces liver enzymesreduces liver enzymes– Stimulates bicarbonate and chloride Stimulates bicarbonate and chloride
secretionsecretion
Image, accessed 11/29/09:http://hdlighthouse.org/treatment-care/_localimages/ursodiol.jpg
Distal intestinal obstruction Distal intestinal obstruction syndrome (DIOS)syndrome (DIOS)
• Obstruction of the right colon and/or Obstruction of the right colon and/or terminal ileum with viscid fecal matterterminal ileum with viscid fecal matter
• Presentation: colicky periumbilcal and/or Presentation: colicky periumbilcal and/or right lower quadrant pain, abdominal right lower quadrant pain, abdominal distension, nausea/vomiting, decreased distension, nausea/vomiting, decreased stool outputstool output
• Risk factors:Risk factors:– PERT non-adherence, dehydration, narcotic PERT non-adherence, dehydration, narcotic
useuse
Distal intestinal obstruction Distal intestinal obstruction syndrome (DIOS)syndrome (DIOS)
• TreatmentTreatment– HydrationHydration– Use of drug therapyUse of drug therapy
• Polyethylene glycol (Miralax®, GoLytely®)Polyethylene glycol (Miralax®, GoLytely®)• EnemasEnemas• N-acetylcysteineN-acetylcysteine
– Surgical resectionSurgical resection
Poor AppetitePoor Appetite1919
• CF anorexia CF anorexia due to:due to:– Elevated serum cytokines due to chronic Elevated serum cytokines due to chronic
infectioninfection– Smell/taste disturbance due to sinusitisSmell/taste disturbance due to sinusitis– GERDGERD– Aggressive nutritional interventionsAggressive nutritional interventions– Behavioral/psychosocial factorsBehavioral/psychosocial factors
• Not all CF patients will require drug Not all CF patients will require drug therapy, but continued nutritional failure therapy, but continued nutritional failure leads to considered added drug therapyleads to considered added drug therapy
Poor Appetite: Appetite Poor Appetite: Appetite StimulantsStimulants1919
• MegesterolMegesterol– Synthetic progestin with antiestrogenic effectsSynthetic progestin with antiestrogenic effects– Cytokine inhibitionCytokine inhibition
• CyproheptadineCyproheptadine– Histamine and serotonin antagonistHistamine and serotonin antagonist– Side effect of appetite stimulationSide effect of appetite stimulation
• DronabinolDronabinol– Psychoactive substance, side effect of appetite stimulationPsychoactive substance, side effect of appetite stimulation
• MirtazipineMirtazipine– Antidepressant, side effect of appetite stimulation and weight Antidepressant, side effect of appetite stimulation and weight
gaingain
CF-Related Diabetes (CFRD)CF-Related Diabetes (CFRD)2020
• Not really Type I or 2 diabetes mellitus…Not really Type I or 2 diabetes mellitus…
• Insulin vs. oral agentsInsulin vs. oral agents– Standard = Insulin (e.g. insulin glargine (long-Standard = Insulin (e.g. insulin glargine (long-
acting) + lispro (intermittent short-acting)) + acting) + lispro (intermittent short-acting)) + carbohydrate countingcarbohydrate counting
– Oral agents not recommended, but Oral agents not recommended, but occasionally usedoccasionally used• Evidence demonstrating efficacy lackingEvidence demonstrating efficacy lacking
• Possible affects of drug therapy on serum Possible affects of drug therapy on serum glucose levelsglucose levels
Other Concurrent Drug TherapyOther Concurrent Drug Therapy• PediatricPediatric
– Psychiatric disordersPsychiatric disorders• Attention deficit hyperactivity disorder (ADHD)Attention deficit hyperactivity disorder (ADHD)• Major depressive disorderMajor depressive disorder
– Seizure disorderSeizure disorder
• AdultAdult– Psychiatric disordersPsychiatric disorders
• Bipolar disorderBipolar disorder• Major depressive disorderMajor depressive disorder
– HypertensionHypertension– HyperlipidemiaHyperlipidemia
““Keep watch also on the fault of Keep watch also on the fault of patients which often make them lie patients which often make them lie
about the taking of things prescribed.” about the taking of things prescribed.”
-Hippocrates-Hippocrates
Physician, Physician, 5 5thth Century BC Century BC
Therapy AdherenceTherapy Adherence
• Adherence to CF treatment continues to Adherence to CF treatment continues to be a challenge be a challenge – Drug therapyDrug therapy– CPTCPT
• Factors in adherenceFactors in adherence– Age-specific Age-specific
• Child vs. adolescence vs. adultChild vs. adolescence vs. adult
– Patient-specificPatient-specific• Patient or caregiver beliefsPatient or caregiver beliefs• FinancialFinancial
Age Specific Factors Age Specific Factors 2121
Infants & Young Children
• Caregiver administration• Caregiver beliefs regarding
medicine, treatment of disease
• Reasons for non-adherence: – Forgetting– Multiple caregivers– D/C due to resolution of
symptoms– Misunderstanding
instructions– Resistance from child– Concern regarding adverse
effects or lack of efficacy
AdolescentsAdolescents
• Patient administration
• Age of “adherence nadir”
• Growing independence vs. parental involvement
• Reasons for non-adherence:– Risk-taking behavior,
invincible perspective– Peer influence– Adverse effects– Forgetting/timing– Psychosocial/psychiatric
issues
What are CF Patients Adherent What are CF Patients Adherent With? With? 2222
Arias Llorente RP. García CB, Díaz Martín JJ. Treatment compliance in children and adults with cystic fibrosis. J Cystic Fib. 2008; 7:359-367.
Children vs. Adolescent Children vs. Adolescent AdherenceAdherence2323
Zindani GN, Streetman DD, Streetman DS, Nasr SZ. Adherence to treatment in children and adolescent patients with cystic fibrosis. J Adolesc Health. 2006 Jan;38(1):13-7.
Group 1:<12 years
Group 2:≥ 12 years
Approaches to Increase Approaches to Increase AdherenceAdherence
• Patient and caregiver educationPatient and caregiver education– School system involvementSchool system involvement
• Assess regimen Assess regimen at visits – create schedule at visits – create schedule to suite patient’s daily routine if possibleto suite patient’s daily routine if possible
• Tools Tools used to measure adherenceused to measure adherence– Medication Event Monitoring System ([MEMS] Medication Event Monitoring System ([MEMS]
APREX, a division of AARDEX, Inc., Union City, APREX, a division of AARDEX, Inc., Union City, California)California)
– Track empty vials? Refills?Track empty vials? Refills?– I-neb™ AAD systemI-neb™ AAD system
CF Interdisciplinary Team CF Interdisciplinary Team Physician Physician Clinical PharmacistClinical PharmacistNurse ClinicianNurse ClinicianClinical DietitianClinical DietitianRespiratory TherapistRespiratory TherapistSocial Worker Social Worker Health Care Trainees (e.g. MSW, MD, RT, Health Care Trainees (e.g. MSW, MD, RT,
PharmD)PharmD)
Role of the Clinical PharmacistRole of the Clinical PharmacistEducate other health care professionals Educate other health care professionals
about therapy options based on the most about therapy options based on the most recent biomedical literature.recent biomedical literature.
Patient/caregiver education regarding Patient/caregiver education regarding mediation use, safety, and efficacy.mediation use, safety, and efficacy.
Recommend and monitor CF regimens Recommend and monitor CF regimens (i.e., kinetics, medication review)(i.e., kinetics, medication review)
Serve as a clinical researcher in Serve as a clinical researcher in evaluating effective and safe treatment evaluating effective and safe treatment options for children, adolescents, and options for children, adolescents, and adults with CF.adults with CF.
My Pathway to Pediatric Pulmonary My Pathway to Pediatric Pulmonary Medicine…Medicine…
My Role at the UA Pediatric My Role at the UA Pediatric Pulmonary CenterPulmonary Center
SummarySummary• CF drug therapy is multi-faceted, often CF drug therapy is multi-faceted, often
involving multiple organ systems with use involving multiple organ systems with use of various dosage forms.of various dosage forms.
• Drug dosing in CF may differ from non-CF Drug dosing in CF may differ from non-CF due to differences in pharmacokinetics due to differences in pharmacokinetics and pharmacodynamics, although much is and pharmacodynamics, although much is still unknown.still unknown.
• Interdisciplinary approach to drug therapy Interdisciplinary approach to drug therapy selection and patient education is selection and patient education is essential to optimize outcomeessential to optimize outcome
ReferencesReferences1. Flume PA, O’Sullivan BP, Robinson KA, et al. Cystic Fibrosis Pulmonary Guidelines: Chronic medications for
maintenance of lung health. Am J Respir Crit Care Med. 2007;176:957-969.2. Nasr SZ, Kuhns LR, Brown RW, Hurwitz ME, Sanders GM, Strouse PJ. Use of computerized tomography and
chest x-rays in evaluating efficacy of aerosolized recombinant human DNase in cystic fibrosis patients younger than age 5 years: a preliminary study. Pediatr Pulmonol. 2001 May;31(5):377-82.
3. Donaldson SH, Bennett WD, Zeman KL et al. Mucous clearance and lung function in cystic fibrosis with hypertonic saline. NEJM. 2006;354:241-250.
4. Elkins MR, Robinson M, Rose BR, et al. A controlled-trial of long-term inhaled hypertonic saline in patients with cystic fibrosis. NEJM. 2006;354:229-240.
5. Konstan MW, Byard PJ, Hoppel CL, Davis PB. Effect of High-Dose Ibuprofen in Patients with Cystic Fibrosis. NEJM. 1995:332;848-854.
6. Clement A, Tamalet A, Leroux E, Ravilly S, Fauroux B, Jais, J-P. Long term effects of azithromycin in patients with cystic fibrosis: a double blind, placebo controlled trial. Thorax 2006;61:895–902. Thorax 2006;61:895–902.
7. Gibson RL, Burns JL, Ramsey BW. Pathophysiology and management of pulmonary infections in cystic fibrosis. Am J Respir Crit Care Med. 2003 Oct 15;168(8):918-51.
8.8. Flume PA, Mogayzel PJ, Robinson KA, Goss CH, Rosenblatt RL, Kuhn RJ, Marshall BC. Clinical Practice Flume PA, Mogayzel PJ, Robinson KA, Goss CH, Rosenblatt RL, Kuhn RJ, Marshall BC. Clinical Practice Guidelines for Pulmonary Therapies Committee. Cystic Fibrosis Pulmonary Guidelines: Treatment of Pulmonary Guidelines for Pulmonary Therapies Committee. Cystic Fibrosis Pulmonary Guidelines: Treatment of Pulmonary Exacerbations. Am J Respir Crit Care Med . 2009; 180:802–808.Exacerbations. Am J Respir Crit Care Med . 2009; 180:802–808.
9. Cystic Fibrosis Foundation Patient Registry. 2001 Annual Data Report to the Center Directors. Bethesda, MD: Cystic Fibrosis Foundation; 2002.
10. Eubanks V, Koppersmith N, Wooldridge N, et al: Effects of megestrol acetate on weight gain, body composition, and pulmonary function in patients with cystic fibrosis. J Pediatr 2002; 140:439-444.
11. Ramsey BW, Pepe MS, Quan JM, et al: Intermittent administration of inhaled tobramycin in patients with cystic fibrosis. N Engl J Med 1999; 340:23
12. Stallings VA, Stark LJ, Robinson KA, Feranchak AP, Quinton H. Evidence-based practice recommendations for nutrition-related management of children and adults with cystic fibrosis and pancreatic insufficiency: results of a systematic review. J Am Diet Assoc 2008;108:832-9.
ReferencesReferences13. Hendeles L, Dorf A, Stecenko A, Weinberger M. Treat-ment failure after substitution of generic pancrelipase
capsules: correlation with in vitro lipase activity. JAMA 1990;263:2459-61.
14. Up-to-Date 2009©. Accessed 11/29/09. Cystic fibrosis: Assessment and management of pancreatic insufficiency. PERT Preparations Table. http://www.utdol.com/online/content/image.do;jsessionid=539B6F5A1A27621314B31A4EB12EB98C.1003?imageKey=PEDS%2F19219.
15. Durie PR, Bell L, Linton W, Corey ML, Forstner GG. Effect of cimetidine and sodium bicarbonate on pancreatic replacement therapy in cystic fibrosis. Gut 1980;21:778-86.
16. Francisco MP, Wagner MH, Sherman JM, Theriaque D, Bowser E, Novak DA. Ranitidine and Omeprazole as Adjuvant Therapy to Pancrelipase to Improve Fat Absorption in Patients With Cystic Fibrosis. J Pediatr Gastroenter Nutr. 2002;35:79-83.
17. Tonelli AR, Drane WE, Collins DP, Nichols W, Antony VB, Olson EL. Erythromycin improves gastric emptying half-time in adult cystic fibrosis patients with gastroparesis. J Cyst Fibros. 2009 May;8(3):193-7.
18. Gumaste V, Baum J. Treatment of gastroparesis: an update. Digestion. 2008;78(4):173-9.
19. Chinuck RS, Fortnum H, Baldwin DR. Appetite stimulants in cystic fibrosis: a systematic review. J Hum Nutr J Hum Nutr Diet. 2007 Dec;20(6):526-37.Diet. 2007 Dec;20(6):526-37.
20. Zirbes J, Milla CE. Cystic fibrosis related diabetes. Paediatr Respir Rev. 2009 Sep;10(3):118-23.
21. Thatcher Shope J. Medication compliance. Pediatr Clin North Am 1981; 28: 5-21.
21. Arias Llorente RP. García CB, Díaz Martín JJ. Treatment compliance in children and adults with cystic fibrosis. J Cystic Fib. 2008; 7:359-367.
22.22. Zindani GN, Streetman DD, Streetman DS, Nasr SZ. Adherence to treatment in children and adolescent Zindani GN, Streetman DD, Streetman DS, Nasr SZ. Adherence to treatment in children and adolescent patients with cystic fibrosis. J Adolesc Health. 2006 Jan;38(1):13-7.patients with cystic fibrosis. J Adolesc Health. 2006 Jan;38(1):13-7.
