1. Challenges of Pharmacotherapy in the Treatment of Cystic Fibrosis
Hanna Phan, Pharm.D.
Clinical Assistant Professor Clinical Pharmacy Specialist, Pediatric Pulmonary Medicine
Residency Program Director, Pediatric Pharmacotherapy Department of Pharmacy Practice and Science
The University of Arizona - College of Pharmacy

2. Objectives
Review common medications used in the outpatient and inpatient settings in the treatment of cystic fibrosis (CF)
Identify challenges of treatment adherence in CF
Understand the role of a clinical pharmacist as part of an interdisciplinary team in management of CF
**Conflict of Interest: I have no relevant financial relationships to disclose for this presentation.

3. Disease Severity, Age, and Therapy
SA, 2 yo ♀
EN, 7 yo ♀
CM, 30 yo ♂
JS, 50 yo ♂
CPT
Creon 12,000
Albuterol
AquADEK liquid
CPT
Creon 12,000
Albuterol
Source CF
Dornase alfa
Tobramycin
Fluticasone NS
Budesonide
CPT
Creon 24,000
Albuterol
Source CF
Dornase alfa
Tobramycin
Azithromycin
Pantoprazole
NaCl 7% Solution
Dronabinol
Megestrol
Ursodiol
Fluticasone NS
Fluticasone/salmeterol
Zolpidem
CPT
Ultrase MT 20
Albuterol
Source CF
Vitamin D
Dornase alfa
Tobramycin
Azithromycin
Pantoprazole
Insulin lispro
Insulin lantus
Clonazepam
Fluticasone/salmeterol
Hydrochlorothiazide
Fluticasone NS
Montelukast
Docusate sodium
CPT = Chest physical therapy

4. CF Drug Therapy Basics
Therapy selection depends on CF severity and organ systems affected
Pulmonary, infectious diseases, etc.
Gastrointestinal, hepatic, etc.
Different pharmacokinetics with CF
Drug selection, dosing, frequency, adverse effects
Off-label medication use
‘Polypharmacy’ is a common concern
Therapy or excessive drug burden
Incorporating therapy as part of everyday life is a challenge in itself

5. Pharmacokinetic Challenges in CF
Absorption
Differences in gastric pH
Slower GI motility
Distribution
Larger volume of distribution
Metabolism
Possible difference in hepatic clearance
Elimination
Increased renal clearance
Absorption
Gastric hyperacidity
Decreased bicarbonate secretion
GERD
Pancreatic insufficiency
Impaired intestinal motility
Affects solubility, rate, extent of absorption  may need higher dose to compensate for poor absorption
Examples:
Reduced absorption of: cyclosporin, tacrolimus,
Slower rate of absorption of: ciprofloxaxin, levofloxacin
Distribution
Increased Vd of β-lactams and aminoglycosides
Therefore, CF patients require larger dose to achieve therapeutic concentrations
Protein binding
Lower albumin in cirrhotic and undernourished patients, not all CF patients
Metabolism
↑ hepatic blood flow?
No effect on CYP 1A2, 2C9, 2D6, 3A4
↑ glucuronidation clearance?
May need higher doses?
Elimination
↑ renal excretion
↑ glomerular filtration rate (GFR)
↑ tubular secretion, ↓ tubular resorption
Lack of controlled studies…
Enhanced clearance of:
Aminoglycosides (renal and non-renal clearance)
Trimethoprim
Ciprofloxacin?
Ceftazidime
Ticarcillin

6. Overall Goals of Therapy
Prolong survival
Optimize/improve quality of life
Slow disease progression
Achieve normal growth and development
Decrease hospitalization frequencies and duration
Minimize adverse drug reactions

7. Pulmonary Drug Therapy

8. Bronchodilators – β agonists1
Nebulized or HFA inhaler
Commonly used as part of CPT
Bronchial hyperresponsiveness, wheezing
Prevent bronchospasm during respiratory therapy and other inhaled treatments
Albuterol
2.5mg nebulized BID (w/ CPT), increased during exacerbation an/or hospitalization
Levalbuterol
When to use versus albuterol?
Why is it not used for everyone?
hydroflouroalkane (HFA) – propellant, used to be chlorofluorocarbons (CFCs)
Images, accessed 11/15/09:

9. Dornase alfa (Pulmozyme®)1,2
Recombinant DNA enzyme
Selectively cleaves extracellular DNA from pulmonary secretions, improve viscoelastic properties of secretions
Promotes airway clearance of mucous  reduce respiratory infection risk
↓ Hospital LOS, duration of IV antibiotics
Given as part of CPT regimen
Recombinant DNA enzyme
Selectively cleaves DNA in pulmonary secretions, improve viscoelastic properties of secretions
Promotes airway clearance of mucous  reduce respiratory infection risk
↓ Hospital LOS, duration of IV antibiotics
reducing viscosity
For use in mild, moderate, and severe CF to improve lung function and reduce exacerbations.
2.5 mg nebulized daily given as part of CPT regimen
Adverse effects
Initial worsening of bronchospasm
Voice alteration/hoarseness
Sore throat & cough
Rash, conjunctivitis
Image, accessed 11/15/09:

10. Hypertonic Saline1,3,4
Increases hydration of airway surface liquid via osmotic flow
Breaks ionic bonds in mucus
Stimulates cilial beat via the release of prostaglandin E2
Helps improve mucociliary clearance
Causes sputum production and cough  improve airway obstruction
Should precede dose with bronchodilator (i.e., albuterol) to decrease incidence of bronchospasm, part of CPT
3% (3.5%) and 7% solutions
Improvement in lung function not as great as dornase alfa, but better than placebo per Cochrane Review in 2005.
People in the study were put into one of two groups. One group inhaled normal saline that was a 0.9% salt solution. The other group inhaled hypertonic saline that was a 7% salt solution. Both groups inhaled a bronchodilator drug (to open airways) then inhaled a sterile salt-water mist using a nebulizer twice a day for a year. During the study, the patients and investigators did not know who was inhaling normal saline and who was inhaling hypertonic saline. Patients were watched closely for any health benefits or any problems while inhaling either solution.
Both groups had better lung function during the study. However, those taking hypertonic saline had even better lung function than the people taking normal saline. Also, it was found that the people in the hypertonic saline group had fewer lung infections than the other group.
We do know that people who are 6 years of age and older, or who have an FEV1 greater than or equal to 40% predicted might be able to take hypertonic saline. Before it can be prescribed, your CF care team will assess you or your child.
Image, accessed 11/15/09:

11. Corticosteroids Inhaled Systemic (oral)
Budesonide (Pulmicort®), Fluticasone (Flovent ®)
Attenuate reactive airways, reduce inflammation
Concurrent asthma
Systemic (oral)
Prednisone
Reduce inflammation (?)
Eigen et al. - Prolonged treatment, alternate-day regimen
Initially appeared to improve pulmonary function and diminish hospitalization rates
Treatment < 24 months at 1mg/kg/day
After 4 years, modest efficacy w/prohibitive side effects, including growth retardation, cataracts, and abnormalities of glucose tolerance
Image, accessed 11/15/09:

12. High-dose Ibuprofen1,5
Inhibits the migration, adherence, swelling, and aggregation of neutrophils, as well as the release of lysosomal enzymes
Decreases rate of decline of FEV1, decreases hospitalizations
Study population…
Requires pharmacokinetic dosing
ADE concerns: GI bleeding
Currently not used in all patients
Started ~1995, used in patients ≥6 years, based on available studies
Use of ibuprofen in cystic fibrosis (CF) began in 1995 with publication of the results of a Cystic Fibrosis Foundation-supported four-year, double-blind, placebo-controlled trial of ibuprofen in people ages 5 to 39 years with CF. The study showed that ibuprofen slowed the rate of pulmonary decline over a four-year period. Those taking ibuprofen also had better growth and were in the hospital less than those who did not take ibuprofen. Everyone had mild lung disease at the start of the study. The effect on pulmonary function took years to show. The people with CF who benefited the most were those who took the drug consistently throughout the four-year study period, and who were younger than 13 years of age when the study began. A study in Canada in people with CF ages 6 to 17 years and data from CF Foundation’s Patient Registry also supports the benefits of ibuprofen in CF.
20-30 mg/kg/dose PO Q12H
Target level mcg/mL (peak)
Should use consistent dosage form
Image, accessed 11/21/09:

13. Azithromycin1,6 “Anti-inflammatory” agent Not “antibiotic prophylaxis”
Immunomodulatory properties
Suppresses inflammation
Alters biofilm formation
Not “antibiotic prophylaxis”
Mon-Wed-Fri regimen
Considerations
Check for presence of atypical mycobacterium
Patient weight
Presence of mucoid P. aeruginosa (but new data!)
Benefit seen w/ ≤ 1 year use (RCT), ages ≥ 6 yr
Improvement in FEV1, improved QOL, fewer courses/days of antibiotics for exacerbations
During the clinical trial, lung function (FEV1), weight, and days spent in the hospital to treat lung infections were watched for changes. The people with CF who were involved in the study were split into two groups. One group took a placebo—an inactive pill that has no treatment value. The other group took azithromycin. During the trial, neither the patient nor the CF researchers knew who took which. Over six months, the group that took the azithromycin saw about a six-percent improvement in their lung function and an increase in their weight. They also spent 47 percent fewer days in the hospital for the treatment of a lung infection.
Use > 1 year - ↑ S. aureus resistance?
Long-term effect requires additional studies
Though the data is considered fair given limited studies and subjects, it is recommended for chronic use in patients ages ≥ 6 yrs to improve lung function and reduce exacerbations.
Azithromycin dosing
< 40 kg  250 mg PO 3x/week
≥ 40 kg  500 mg PO 3x/week
Image, accessed 11/21/09:

14. Antimicrobial Therapy7,8
Intravenous (IV), oral (PO), or nebulized (NMT) route
Treatment (mean duration ~ days)
Prophylaxis (outpatient, on/off months)
Factors affecting antibiotic selection:
Cultures and susceptibilities (past and present)
Often more than one pathogen…
Age
Child vs. adolescent vs. adult
Organ function (i.e., renal, hepatic)
History of allergies and adverse drug events

15. P. aeruginosa S. aureus CF - Resident Primer
Age-specific prevalence of airway infections in patients with CF. Organisms reported to the U.S. Cystic Fibrosis Patient Registry, 2001.
Overall percentage of patients (all ages) who had at least one respiratory tract culture (sputum, bronchoscopy, oropharyngeal, or nasal) performed in
2001 that was positive for the following organisms: Pseudomonas aeruginosa (red line), 58.7%; Staphylococcus aureus (green line), 48.0%; Haemophilus influenzae (dark blue line), 15.9%; Stenotrophomonasmaltophilia (yellow line), 8.4%; Achromobacter xylosoxidans (light
blue line), 4.4%; Burkholderia cepacia (black line), 3.1%.
P. aeruginosa and S. aureus have enhanced ability to bind to the CF airway epithelium because of the altered CF mucus, higher mucus osmolarity, or altered glycoconjugate composition of the airway cells.
Resistant pathogens are common
9Cystic Fibrosis Foundation Patient Registry Annual Data Report to the Center Directors. Bethesda, MD: Cystic Fibrosis Foundation; 2002.
7Gibson RL, Burns JL, Ramsey BW. Pathophysiology and management of pulmonary infections in cystic fibrosis. Am J Respir Crit Care Med Oct 15;168(8):
H.Phan, PharmD

16. Antibiotics for CF Exacerbation7,8
Multi-drug resistant (MDR) pathogens are common
2+ drug therapy approach
From different drug classes
Outpatient
Oral agent(s) + nebulized agent + increased CPT
IV agent(s) ± oral agent(s) ± nebulized agent + increased CPT
Inpatient

17. Commonly Used Antibiotics in CF: Oral Agents7,8
S. aureus
Methicillin-susceptible (MSSA)
Cephalexin, amoxicillin/clavulanate
Methicillin-resistant (MRSA)
Sulfamethoxazole/trimethoprim, clindamycin, linezolid
P. aeruginosa
Ciprofloxacin
H. influenzae
Amoxicillin/clavulanate, cefuroxime

18. Commonly Used Antibiotics in CF: Nebulized Agents 7,8
P. aeruginosa
Tobramycin solution (TOBI®)
Colistimethate (colistin)

19. Commonly Used Antibiotics in CF: IV Agents7,8
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

20. Commonly Used Antibiotics in CF: IV Agents7,8
Pathogen
Antimicrobial
S. maltophilia
Sulfamethoxazole / trimethoprim
Piperacillin / tazobactam
Levofloxacin or moxifloxacin
Ticarcillin / Clavulanate + aztreonam
H. influenzae
All drugs listed for P. aeruginosa provide coverage (rec. 3rd gen cephalosporin), may not need for double coverage combination

21. Commonly Used Antibiotics in CF: IV Agents7,8
Pathogen
Antimicrobial
B. cepacia
Sulfamethoxazole / 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

22. Scedosporium apiospermum
Antifungal Agents7,8
Pathogen
Antifungal
Candida spp. (most)
Fluconazole
 Aspergillus spp.
Itraconazole
Voriconazole
Scedosporium apiospermum

23. Antibiotic Prophylaxis1,11
Some patients may be given oral antibiotic therapy for prophylaxis (rare)
Most common form is nebulized antibiotics
Tobramycin solution (TOBI®)
Colistimethate (colistin)
The above are given twice a day, 28 days on/off schedule

24. Gastrointestinal and Nutritional Drug Therapy

25. Concurrent GI/Nutrition Issues
Malabsorption (pancreatic insufficency)
Gastroesophageal reflux disease (GERD)
Gastroparesis
Hepatobiliary disease
Distal intestinal obstruction syndrome (DIOS)
Poor intake/appetite
CF related diabetes (CFRD)

26. Pancreatic Insufficiency12,13
Pancreatic enzyme replacement therapy (PERT)
Several manufacturers
Creon®, Pancrease®, Pancrearb®, Ultrase®, Viokase®, ZenPep®, Pangestyme™
FDA Ruling
All manufacturers of pancreatic enzyme products must secure FDA approval of their products by submitting New Drug Application by 4/2009 in order to remain available to patients

27. PERT Products14 Image, accessed 11/29/09: Up-to-date 2009 ©

28. Pancreatic Insufficiency12
Nutritional supplements
Fat-soluble vitamins
Vitamins A, D, E, and K
ADEK®, AquADEK®, SourceCF®
Vitamin D
Ergocalciferol
Vitamin E
Over the counter supplement formulations (capsules)
Iron supplements
Ferrous sulfate, ferrous gluconate
Considerations with GERD medications…
A – bone development/growth, normal vision, reproduction, proper immune function, cofactor
D – bone development
E – antioxidant
K – coagulation, bone development

29. Gastroesophageal reflux disease (GERD)15,16
> 25-30% incidence
Histamine-2 receptor antagonists (H2RA)
Famotadine
Ranitidine
Proton pump inhibitors (PPI)
Pantoprazole,lansoprazole,
omeprazole, esomeprazole
“Enzyme Boosting”
Images, accessed 11/29/09:

30. Gastroparesis17,18 Often related to CFRD
Affects the ability of the stomach to empty its contents
No blockage (obstruction)
Drug therapy that helps nausea/vomiting
Ondansetron (Zofran®)
Prochlorperazine (Compazine®)
Drug therapy can help increase motility
Metoclopramide (Reglan®)
Erythromycin (E-Mycin®)

31. Hepatobiliary Disease
Up to 30% incidence, usually later in life
Bile duct obstruction from abnormal bile composition and flow (cholestasis)
Potential complications:
Cirrhosis
Biliary colic secondary to cholelithiasis
Portal hypertension  liver transplant
Biliary duct obstruction  chronic inflammation

32. Hepatobiliary Disease19,20
Drug therapy: Ursodiol
Ursodeoxycholic acid
30 mg/kg/day BID (max 300 mg PO BID)
Clinical effects
Slows progression of disease, improves bile flow
Displaces toxic bile acids and reduces liver enzymes
Stimulates bicarbonate and chloride secretion
Image, accessed 11/29/09:

33. Distal intestinal obstruction syndrome (DIOS)
Obstruction of the right colon and/or terminal ileum with viscid fecal matter
Presentation: colicky periumbilcal and/or right lower quadrant pain, abdominal distension, nausea/vomiting, decreased stool output
Risk factors:
PERT non-adherence, dehydration, narcotic use

34. Distal intestinal obstruction syndrome (DIOS)
Treatment
Hydration
Use of drug therapy
Polyethylene glycol (Miralax®, GoLytely®)
Enemas
N-acetylcysteine
Surgical resection

35. Poor Appetite19 CF anorexia due to:
Elevated serum cytokines due to chronic infection
Smell/taste disturbance due to sinusitis
GERD
Aggressive nutritional interventions
Behavioral/psychosocial factors
Not all CF patients will require drug therapy, but continued nutritional failure leads to considered added drug therapy

36. Poor Appetite: Appetite Stimulants19
Megesterol
Synthetic progestin with antiestrogenic effects
Cytokine inhibition
Cyproheptadine
Histamine and serotonin antagonist
Side effect of appetite stimulation
Dronabinol
Psychoactive substance, side effect of appetite stimulation
Mirtazipine
Antidepressant, side effect of appetite stimulation and weight gain

37. CF-Related Diabetes (CFRD)20
Not really Type I or 2 diabetes mellitus…
Insulin vs. oral agents
Standard = Insulin (e.g. insulin glargine (long-acting) + lispro (intermittent short-acting)) + carbohydrate counting
Oral agents not recommended, but occasionally used
Evidence demonstrating efficacy lacking
Possible affects of drug therapy on serum glucose levels

38. Other Concurrent Drug Therapy
Pediatric
Psychiatric disorders
Attention deficit hyperactivity disorder (ADHD)
Major depressive disorder
Seizure disorder
Adult
Bipolar disorder
Hypertension
Hyperlipidemia
Need to consider other concurrent drug therapy when adding new medications (e.g. CF exacerbations and antibiotics or antifungals) due to possibility of drug interactions.

39. “Keep watch also on the fault of patients which often make them lie about the taking of things prescribed.” -Hippocrates Physician, 5th Century BC
“Keep watch also on the fault of patients which often make them lie about the taking of things prescribed.” (Hippocrates, a Greek Physician, 5th century BC)

40. Therapy Adherence
Adherence to CF treatment continues to be a challenge
Drug therapy
CPT
Factors in adherence
Age-specific
Child vs. adolescence vs. adult
Patient-specific
Patient or caregiver beliefs
Financial

41. Infants & Young Children
Age Specific Factors 21
Infants & Young Children
Adolescents
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
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
DM patients at least 28% of patients not adhering, adherence lowest amongst cancer patients during adolescence.
Discuss stories of parents who believe treatment in hospital plus a few weeks of outpatient inhaler use cures asthma
Discuss The Spirit Catches You and You Fall Down (literal definition of epilepsy in Hmong), by Anne Fadiman tells the story of Lia Lee, a young Hmong girl whose epilepsy was diagnosed in Merced, California.
The most important lesson is the necessity of seeing a case from the patient's point of view. Even if the doctor's knowledge exceeds the patient's by an incalculably huge factor, that knowledge will do little good if the patient does not trust the doctor or if the doctor does not understand the patient. The best remedy for both those problems is for the doctor to look at things from the patient's perspective (which may be culturally influenced).

42. What are CF Patients Adherent With? 22
Objectives: To determine treatment compliance and how compliance was perceived by patients, parents and by a multidisciplinary team in Cystic
Fibrosis (CF) patients. Also to analyse the relative importance given to each of the prescribed treatments, reasons for non-adherence and to
investigate possible predictors of therapeutic compliance.
physiotherapy, respiratory medication (including DNase, antibiotics, and inhaled corticosteroids), digestive medication (including pancreatic enzymes, vitamins, deoxycholic acid, and antacids) and
nutritional supplements.
Patients and methods: 34 CF patients (21 females), aged between 1.6 and 40.6 years, attending an outpatient CF clinic. Design: cross-sectional. A
self-administered questionnaire was given to all patients whilst attending a programmed visit which was used to determine compliance to different
treatments (physiotherapy, nutritional supplements, respiratory and digestive medications). Patients were subjectively classified as compliant or
non-compliant by medical staff involved in their care.
Results: Treatment compliance was greater for digestive (88.2%) and respiratory medication (61.8%), compared to physiotherapy (41.2%) or
nutritional supplements (59%). CF patients considered digestive medication indispensable (94.1%), compared to nutritional supplements
(44.1%). Whilst 26.4% of CF patients considered that respiratory medications or nutritional supplements influenced little or nothing in their
quality of life. Comparing age groups younger patients were found to be more compliant (10.4 vs years p=0.008) and had less severe
disease (Shwachman score 83.2 vs p=0.048).
Conclusions: CF patients had greater treatment adherence when prescribed digestive and respiratory medications, compared to physiotherapy or
nutritional supplements. Therapeutic adherence was found to worsen with age and disease severity, however improved with treatments which were
perceived by patients as more important or had a greater influence in their quality of life.
Arias Llorente RP. García CB, Díaz Martín JJ. Treatment compliance in children and adults with cystic fibrosis. J Cystic Fib ; 7:

43. Children vs. Adolescent Adherence23
Group 1:
<12 years
Group 2:
≥ 12 years
Purpose: The purpose of this study was to monitor medication adherence in cystic fibrosis (CF)
patients and its correlation with disease severity and patient age.
Methods: Children less than 12 years of age (group 1) and adolescents 12 years of age and older (group
2) were recruited from the University of Michigan CF Center. The study duration was 3 months. A total
of 22 patients per group were enrolled. Adherence to ADEKs, an oral multivitamin, and dornase alfa, a
nebulized mucolytic medication, was monitored. Adherence to ADEKs was monitored by using the
Medication Event Monitoring System (MEMS) SmartCaps (APREX, AARDx, Inc., Union City, California).
Dornase alfa adherence rate was monitored by counting empty medication vials.
Results: Thirty-three patients completed the study, 15 patients in group 1 and 18 patients in group
2. The overall mean adherence rates for ADEKs and dornase alfa were ( SD) 63.6% 24.0% and
66.5% 31.2%, respectively. The median ADEKs and dornase alfa adherence rate for group 1 was
84.6% and 79.1%, respectively (p .08); and for group 2 was 56.7% vs. 78.4%, respectively (p
.07). There was a trend toward significance, suggesting that the adherence rate for ADEKs was
higher than for dornase alfa (p .08) in group 1. Group 2 showed a trend toward adherence to
dornase alfa than to ADEKs (p .07). There was a trend for ADEKs adherence between groups 1
and 2 (p .09), but not for dornase alfa (p .93).
Conclusion: Parental supervision and disease severity are likely to play a major role in adherence
to medical management. Partnership with patients and families about the treatment plan might be
important for improving adherence rate. The MEMS SmartCaps is an electronic monitoring technology
that should be used to measure drug adherence objectively both in further larger clinical trials
and in the outpatient setting.
Zindani GN, Streetman DD, Streetman DS, Nasr SZ. Adherence to treatment in children and adolescent patients with cystic fibrosis. J Adolesc Health Jan;38(1):13-7.

44. Approaches to Increase Adherence
Patient and caregiver education
School system involvement
Assess regimen at visits – create schedule to suite patient’s daily routine if possible
Tools used to measure adherence
Medication Event Monitoring System ([MEMS] APREX, a division of AARDEX, Inc., Union City, California)
Track empty vials? Refills?
I-neb™ AAD system
In contrast to standard
nebulisers which deliver a constant flow of aerosol, the I-neb
only releases medication during inspiration, providing a more
efficient delivery of drug to the lungs. Since its introduction,
adherence data have been routinely downloaded, monitored and
shared with patients/parents in the clinic and used to inform
clinical decision making if appropriate.

45. CF Interdisciplinary Team
Physician
Clinical Pharmacist
Nurse Clinician
Clinical Dietitian
Respiratory Therapist
Social Worker
Health Care Trainees (e.g. MSW, MD, RT, PharmD)

46. Role of the Clinical Pharmacist
Educate other health care professionals about therapy options based on the most recent biomedical literature.
Patient/caregiver education regarding mediation use, safety, and efficacy.
Recommend and monitor CF regimens (i.e., kinetics, medication review)
Serve as a clinical researcher in evaluating effective and safe treatment options for children, adolescents, and adults with CF.

47. My Pathway to Pediatric Pulmonary Medicine…
Undergraduate studies
(The University of Michigan)
Doctor of Pharmacy (PharmD)
4 years
Clinical Practice
(Pediatrics, NICU)
3 years
Postdoctoral Fellowship
(The Ohio State University, The Research Institute at Nationwide Children’s Hospital)
2 years
Clinical Assistant Professor and Clinical Pharmacy Specialist
(The University of Arizona, College of Pharmacy)
Continued scholarship, practice, and teaching in pediatric pharmacotherapy with focus in pulmonary medicine
Previous to my fellowship, my research was primarily medication safety (ValiMed, fluorometer used to check iv medications prior to dispensing in a pediatric hospital).
During fellowship, I broaded my research to include review of off-label medications used in special patient popualations (neonates) with interest in infectious diseases (nebulized AMG for tracheitis), OL med safety in peds ER, health literacy of caregivers of children regarding asthma, diabetes. My service was the general pediatrics, peds pulmonary, and peds infectious diseases as well as an asthma and adhd clinic (Fridays, 1/2 days) within an outpatient general pediatrician clinic.
Now, my area of interest is more focused, in pediatric pulmonary, with emphasis in CF and asthma. I am currently exploring my research options in pharmacogenomics (application in medication safety, prediction of ADR and efficacy as a pair) and medication adherence in asthma and CF.
I also train pharmacy trainees, both student and postgraduate as a faculty member at the COP and as residency director of the pediatric specialty pharmacy residency program, which will have its first trainee in July 2010.

48. My Role at the UA Pediatric Pulmonary Center
CF Clinic
Intake and assessment of medication regimens
Assessment of adherence
Recommend drug therapy for maintenance and exacerbations
Education
Inpatient
Notified of new admissions to UMC
Evaluate and assess patient data (e.g., cultures) and recommend initial antimicrobial regimen and lab monitoring parameters
Weekly rounding with team to assess progress and recommend any changes in therapy
Scholarship and Education
Participate in research in the ARC
Asthma CF
Participate in the education of health care professional trainees
Fellows
Residents
Students
PPC trainees

49. Summary
CF drug therapy is multi-faceted, often involving multiple organ systems with use of various dosage forms.
Drug dosing in CF may differ from non-CF due to differences in pharmacokinetics and pharmacodynamics, although much is still unknown.
Interdisciplinary approach to drug therapy selection and patient education is essential to optimize outcome

50. Questions?

51. References
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 ;176:
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 May;31(5):
Donaldson SH, Bennett WD, Zeman KL et al. Mucous clearance and lung function in cystic fibrosis with hypertonic saline. NEJM. 2006;354:
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:
Konstan MW, Byard PJ, Hoppel CL, Davis PB. Effect of High-Dose Ibuprofen in Patients with Cystic Fibrosis. NEJM. 1995:332;
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.
Gibson RL, Burns JL, Ramsey BW. Pathophysiology and management of pulmonary infections in cystic fibrosis. Am J Respir Crit Care Med Oct 15;168(8):
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 Exacerbations. Am J Respir Crit Care Med ; 180:802–808.
Cystic Fibrosis Foundation Patient Registry Annual Data Report to the Center Directors. Bethesda, MD: Cystic Fibrosis Foundation; 2002.
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:
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
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.

52. References
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:
Up-to-Date 2009©. Accessed 11/29/09. Cystic fibrosis: Assessment and management of pancreatic insufficiency. PERT Preparations Table.
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:
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.
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 May;8(3):193-7.
Gumaste V, Baum J. Treatment of gastroparesis: an update. Digestion. 2008;78(4):173-9.
Chinuck RS, Fortnum H, Baldwin DR. Appetite stimulants in cystic fibrosis: a systematic review. J Hum Nutr Diet Dec;20(6):
Zirbes J, Milla CE. Cystic fibrosis related diabetes. Paediatr Respir Rev Sep;10(3):
Thatcher Shope J. Medication compliance. Pediatr Clin North Am 1981; 28: 5-21.
Arias Llorente RP. García CB, Díaz Martín JJ. Treatment compliance in children and adults with cystic fibrosis. J Cystic Fib ; 7:
Zindani GN, Streetman DD, Streetman DS, Nasr SZ. Adherence to treatment in children and adolescent patients with cystic fibrosis. J Adolesc Health Jan;38(1):13-7.