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Cystic Fibrosis Module #2: Chronic Medications: Changing the Course of Cystic Fibrosis

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Chronic Medications: Changing the Course of Cystic Fibrosis

Dr. Jeffery T. Zobell, Pharm.D., BCPPSDr. David C. Young, Pharm.D.

Objectives

• Discuss current guideline recommendations regarding chronic medication use in patients with CF

• Review the current evidence and future directions regarding chronic medications in patients with CF


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Areas Where Drug Therapy Exists

Cystic Fibrosis

Gastrointestinal Endocrine Pulmonary

Pulmonary Pathogenesis

• Primary cause of morbidity & mortality– ~90% of fatalities

• Hypotheses have been proposed to explain the pulmonary pathogenesis

• Steps have been recognized as targets for therapeutic interventions

Flume et al., Am J Respir Crit Care Med 2009; 180:802–808


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Thick viscous secretions

Bronchial Obstruction

Activation of airway inflammatory cells (PMNs)

Infection

Inflammation

Bronchiectasis

Targets of Existing Therapy

NonpharmacologicChest physiotherapy, Vest

• Nutrition• Physical activity• Psychosocial• Airway clearance

– Chest physiotherapy (CPT)– Positive expiratory pressure (PEP) devices– High-frequency chest wall oscillation systems

(Vest)

Yankaskas et al. Chest. 2004 Jan;125(1 Suppl):1S-39S.

Non-pharmacologic


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Chronic CF Therapies – Recommended Order

Aerosolized antibiotics

Airway clearance

Dornase alfa

Hypertonic saline

Bronchodilator

Mogayzel PJ, et al. Am J Respir Crit Care Med. 2013;187(7):680-689.




Infection

Inflammation

Bronchiectasis

Targets of Existing TherapyBronchodilators

Albuterol, Levalbuterol, Salmeterol, Formoterol, Arformoterol, Indacaterol, Olodaterol, Ipratropium, Tiotropium


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Chronic Inhaled Beta2 agonists (albuterol, levalbuterol, formoterol,olodaterol)

• 50 to 60% of CF patients have significant intermittent reactive airways

• May provide benefit for CF patients with airway hyper-responsiveness

• Insufficient evidence to recommend for or against chronic, daily use in CF pts > 6 yrs

Mogayzel P et al. Am J Respir Crit Care Med 2013 187(7):680–689

Chronic Inhaled Anticholinergics(ipratropium, tiotropium)

• Insufficient evidence to recommend for or against chronic, daily use in CF pts > 6 yrs

• Ratjen et al. 2015– ↑ FEV1 AUC0–4 h of 2.62% in pooled phase 2/3

trial tiotropium vs placebo CF pt >5yrs

• Brandt et al. 2016– Adult CF pt w/FEV1 >70% improvement annual

FEV1 decline (3.5%)

Brandt C et al. PLoS One. 2016 Jun 28;11(6):e0158193Mogayzel P et al. Am J Respir Crit Care Med 2013 187(7):680–689Ratjen F et al. J Cyst Fibros. 2015 Sep;14(5):608-14


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Inhaled Bronchodilators Evidence Summary

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?• Insufficient evidence to

recommend for or against chronic, daily use in CF pts > 6 yrs

Future • Chronic, daily use in CF pts > 6 yrs




Infection

Inflammation

Bronchiectasis


MucolyticsDornase alfa, Hypertonic saline


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Hypertonic Saline (Sodium chloride, HyperSal®, Nebusal®, Pulmosal®)• Dose: 4 mL nebulized twice daily• Available in 3, 3.5, 6, 7, & 10% / 4ml• CFF recommends chronic use >6yrs

– ↑ FEV1 (3-12%), QOL(?)– ↓ pulmonary exacerba ons (56%)

• Adverse effects– Bronchospasm

• Administer albuterol/levalbuterol prior to hypertonic saline to prevent bronchospasm

Flume P et al. Am J Respir Crit Care Med 2007 176:957–969Mogayzel P et al. Am J Respir Crit Care Med 2013 187(7):680–689

• Rosenfeld, et al. 2012 – No change in APE in pts 4-60months

• Rosenfeld, et al. 2015– Currently enrolling phase 2 study hypertonic

saline in pts 3-5yrs

Hypertonic saline

Rosenfeld M, et al. JAMA 2012;307(21):2269-2277ClinicalTrials.gov Identifier: NCT02378467


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• CF pts > 6 yrs w/FVC >40% – FDA approved >5yrs

• 2.5mg nebulized every day – Moderate-severe disease

• ↑ FEV1 (6%), ↑ Increase QOL• ↓ APE (28%)

– Mild disease• ↑ FEV1 (3%), ↑ Increase QOL• ↓ APE (34%)

Dornase alfa (Pulmozyme®)

Flume P et al. Am J Respir Crit Care Med 2007 176:957–969Mogayzel P et al. Am J Respir Crit Care Med 2013 187(7):680–689

• Yang, et al. 2016 – ↑ FEV1 (4-10% in trials of 1 mo-2yrs),– ↑ QOL– ↓ APE (22% up to 2yrs)– Cost savings offset 18-38% of med cost

• Dentice, et al. 2016– “Timing of dornase alfa inhalation (before or after

airway clearance or the time of day) can be based on practical reasons or individual preference “

Dornase alfa (Pulmozyme®)

Yang C, Chilvers M, et al. Cochrane Database of Systematic Reviews 2016Dentice R, Elkins M. Cochrane Database of Systematic Reviews 2016


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Chronic CF Therapies – Recommended Order

Aerosolized antibiotics

Airway clearance

Dornase alfa

Hypertonic saline

Bronchodilator

Dentice R, Elkins M. Cochrane Database of Systematic Reviews 2016

Dornase alfa (Pulmozyme®)• Adverse effects

– voice alteration, pharyngitis, rash, laryngitis, chest pain, conjunctivitis, rhinitis, decrease in FVC of ≥10%, fever, and dyspnea

• Storage/Stability– In refrigerator (2-8°C/36-46°F)– Ampules should be protected from strong light– Do not use beyond the expiration date stamped

on the ampule

Lexi-Drugs Online. Hudson, Ohio: Lexi-Comp, Inc.; June 2016


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• Aitken, et al. 2012 – Double-blind, randomized, controlled– >6yrs; FEV1 30-89%; N=318– 400mg BID vs placebo x 26 weeks + 26 weeks open

label– ↑ Increase relative FEV1 (3.75%)– No difference in APE, hospitalizations, QOL

• Aitken, et al 2014– Currently enrolling phase 3 study inhaled dry

powdered mannitol in pts >18yrs w/ FEV1 40-90%

Inhaled Dry Powdered Mannitol

Aitken M et al. Am J Respir Crit Care Med. 2012 Mar 15;185(6):645-52ClinicalTrials.gov identifier: NCT02134353

Mucolytics Evidence Summary

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Yes

• Hypertonic saline in pts > 6yrs• Dornase alfa in pts > 6yrs with moderate to

severe dx• Dornase alfa in pts > 6yrs with mild dx

Future

• Hypertonic saline in pts 3-5yrs with FEV1 <99% (Phase 2)

• Inhaled dry powdered mannitol in pts >18yrs w/ FEV1 40-90% (Phase 3)


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Infection

Inflammation

Bronchiectasis


Antimicrobials

Inhaled tobramycin;

Inhaled aztreonam;

IV antibiotics

Aerosolized ABX in CFAminoglycosides β-Lactams Quinolone Others

Amikacin Aztreonam Levofloxacin Colistimethatesodium

Tobramycin Ciprofloxacin Vancomycin


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Tobramycin inhaled solution (TIS)Guideline Dose Dose Interval

(hrs)Comments

CFF (Mogayzel et al.) 300mg BID 28days on/28 days off

UK CF Trust 300mg BID 28days on/28 days off

Initial treatmentshould be nebulized colistin

European Consensus (Heijerman et al.)

300mg BID 28days on/28 days off

CFF, 1994; Mogayzel et al. 2013; UK CF Trust 2009; Doring et al. 2000; Heijerman et al. 2009

Tobramycin (TOBI®, TOBI Podhaler®, Bethkis®,Kitabis®)Medication Indication Dosage Adverse effectsTobi® >6yrs with

P. aeruginosa (FEV1 25%-75%)

300mg/5ml nebulized BID 28days on/off via DeVilbiss Pulmo-Aide Compressor + Pari LC+ nebulizer

Voice alteration, tinnitus

Bethkis® >6yrs with P. aeruginosa (FEV1 40%-80%)

300mg/4ml nebulized BID 28days on/off via Pari VIOS Air Compressor + Pari LC+ nebulizer

↓ FEV1, rales, dysphonia

Kitabis® >6yrs with P. aeruginosa (FEV1 25%-75%)

300mg/5ml nebulized BID 28days on/off via DeVilbiss Pulmo-Aide Compressor + Pari LC+ nebulizer (co-packaged)

cough, pharyngitis, ↑ sputum

Tobi Podhaler® >6yrs with P. aeruginosa (FEV1 25%-80%)

112 mg (4 x 28 mg capsules) inhaledBID BID 28days on/off

cough, lung disorder, productive, dyspnea, pyrexia, oropharyngeal pain, dysphonia, hemoptysis, and headache



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Tobramycin (TOBI®, TOBI Podhaler®, Bethkis®,Kitabis®)

• TOBI®, Bethkis®,Kitabis®– Storage/Stability

• refrigeration at 2°C to 8°C (36°F to 46°F). May be stored in foil pouch (opened or unopened) at room temperature of 25°C (77°F) for up to 28 days. Protect from light. The colorless to pale yellow solution may darken over time if not stored under refrigeration; however, the color change does not affect product quality. Do not use if solution has been stored at room temperature for >28 days.

• TOBI Podhaler®– Storage/Stability

• Store in original package at 25°C (77°F); excursions permitted to 15°C to 30°C (59°F to 86°F). Protect from moisture.


Tobramycin solution EvidenceTrial Treatment/ Study Design Outcomes

Ramsey BW et al. 1999n=520 pts

Tobramycin 300 mg BID – 28 days on and 28 off for 24 wksRDBPCT, Multicenter

FEV-1 (p<0.001); in density of P. aeruginosa (p<0.001), hospitalizations (26% reduction)

MacLusky IB et al. 1989n=27 pts

Tobramycin 80 mg TID for 32 mo;RPBPCT

PF in 6/15 in tx group and 11/12 in control; resistance in 4/12 in tx and 0/12 in placebo

Ramsey BW et al. 1993n=71 pts

Tobramycin 600 mg TID – 28 days on and 2x28 days off (or 28 days off and 2x28 days on); RDBPCT 3 period crossover; Multicenter

FEV1 (p<0.001) by 9.7% and in sputum density of P. aeruginosa (p<0.001)

Gibson RL et al. 2003n=21 pts (age 6mo-6yrs)

Tobramycin 300 mg BID for 28 days; RDBPCT; Multicenter

Eradication of colonization in 8/8 tx (5 with mucoid strain) and 1/13 of placebo; no difference in markers of inflammation – Study terminated early

Murphy TD et al. 2004n=400 pts (age 6-15yrs)

Tobramycin 300 mg BID for 28 days on 28 days off; RCT; Multicenter

2.42-fold risk of hospitalization– study terminated early; Abx (p=0.009)

Treggiari MM et al. 2011n=304 (age 1-12yrs)

Tobramycin 300 mg BID – 28 days on and PO Ciprofloxacin 15-20mg/kg BID -14 days for 18 mo; RPCT, Multicenter

No difference in exacerbation rates or prevalence of P. aeruginosa


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Tobramycin powder EvidenceTrial Treatment/ Study Design Outcomes

Galeva I et al. 2013n=62 (6-21yrs)

TIP 112mg BID – 28 days on and 28days off; RDBCT, Multicenter

FEV-1 (p<0.05); in density of P. aeruginosa (p=0.002)

Konstan M et al. 2010 n=95 (6-21yrs)

TIP 112mg BID – 28 days on and 28days off for 3 cycles; RDBCT, Multicenter

FEV-1 (p<0.002) ; in density of P. aeruginosa, hospitalizations, and need for IV ABX

Konstan M et al. 2011n=517 (>6yrs)

TIP 112mg or TIS 300 mg BID – 28 days on and 28days off for 3 cycles; Rand, Open-label, Multicenter

No difference in FEV-1 or sputum density of P. aeruginosa; Administration time significantly less with TIP (5.6min vs. 19.7min; p<0.0001)

• Ramsey B, et al. 2014 (OPTIMIZing)– Currently enrolling phase 3 study pts 6mo-18yrs– TIS +/- Azithromycin in pts with early isolation of

P. aeruginosa• Nichols D, et al. 2016 (TEACH-IP-15)

– Currently enrolling phase 2 study pts >12yrs– TIS + Azithromycin P. aeruginosa w/ FEV125-

100%

Tobramycin inhaled

Ramsey B, et al. ClinicalTrials.gov Identifier: NCT02054156Nichols D, et al. ClinicalTrials.gov Identifier:NCT02677701


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Tobramycin Evidence Summary

Yes• Pts > 6yrs with moderate to severe dx with chronic P. aeruginosa

Yes?• Pts > 6mo with mild dx with chronic P. aeruginosa• Pts > 6mo with early P. aeruginosa

Future?

• Pts > 6mo-18yrs with early P. aeruginosa TIS +/- Azithromycin (Phase 3)• Pts > 12yrs TIS + Azithromycin P. aeruginosa w/ FEV125-100% TIS +

Azithromycin (Phase 2)

Guideline Dose Dose Interval (hrs)

Comments

CFF (Mogayzel et al.) 75mg TID 28days on/28 days off

UK CF Trust N/A

European Consensus (Heijerman et al.)

75mg TID 28days on/28 days off


Aztreonam solution


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Aztreonam (Cayston®)• Indicated for management of CF patients (>7yrs) with P. aeruginosa

(FEV1>25%<75%)• 75mg/1ml nebulized TID via Cayston Altera for 28 days; Then OFF 28 days• Adverse effects

– Cough, nasal congestion, wheezing, oropharyngeal pain, pyrexia, chest discomfort, abdominal pain and vomiting

• Storage/Stability– In refrigerator (2-8°C or 36-46°F) or until expiration date. Opened

or unopened pouches at room temperature (up to 25°C/77°F) for up to 28 days.

– Avoid exposing ampules to intense light. – You should not use Cayston if it is cloudy, if there are particles in the

solution, or if it has been stored at room temperature for more than 28 days. You should not use Cayston beyond the expiration date stamped on the ampule.


Aztreonam solution Evidence

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Trial Treatment/ Study Design Outcomes

McCoy et al. 2008n=211 (>6yrs)

AZLI 75mg BID or TID – 28 days on and monitored for 56days; RDBCT, Multicenter

Time to next abx (p=0.007); FEV-1 (p=0.001); in density of P. aeruginosa (p=0.006)

Retsch-Bogart et al. 2009n=164 (>6yrs)

AZLI 75mg TID – 28 days on and monitored for 14days; RDBCT, Multicenter

FEV-1 (p<0.001); in density of P. aeruginosa (p<0.001)

Assael BM et al. 2012n=273 (>6yrs)

AZLI 75mg TID vs. TIS TID– 28 days on/28 days off for 3 cycles; RDBCT, Multicenter

Mean change in FEV-1 >AZLI (p=0.002); in hospitalizations, need for abx (p=0.044; p=0.004)

Wainright CE et al. 2011n=157 (>6yrs; FEV-1>75%)

AZLI 75mg TID vs. TIS TID– 28 days on/28 days off for 3 cycles; RDBCT, Multicenter

FEV-1 (p<0.021); in density of P. aeruginosa (p<0.001)


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• Tiddens H, et al. 2015 (ALPINE)– 3 mo-18yrs w/ new onset P. aeruginosa w/FEV1>80%– AZLI 75mg neb TID 28-day– 89.1% (n=90) were free of Pa at the end of treatment and

75.2% (n=76) were free of Pa 4 weeks after the end of treatment

• Tullis E, et al. 2014– >6yrs w/ chronic B. cepacia w/FEV1>80%– AZLI 75mg neb TID 24-weeks– No significant treatment differences (AZLI vs. placebo) were

observed at week 24 for any endpoints, including FEV1% predicted, number of respiratory exacerbations requiring systemic/inhaled antibiotics, or hospitalizations

Aztreonam inhaled

Tiddens H, et al. J Cyst Fibros. 2015 Jan;14(1):111-9.Tullis E, et al. J Cyst Fibros 2014;13(3):296-305

Aztreonam Evidence Summary

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Yes• Pts > 6yrs with moderate to severe dx with chronic

P. aeruginosa infection

Yes?• Pts > 6yrs with mild dx with chronic P. aeruginosa

infection

Future ?

• Pts 3mo<18yrs with new onset P. aeruginosa w/FEV1>80%

• Pt > 6yrs with P. aeruginosa w/FEV1 25-75% continuous alternating therapy (Phase 3)


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Colistimethate sodium (CMS)Guideline CMS Dose

(mg)Dose Interval (hrs)

Comments

CFF (Mogayzel et al.) N/A

UK CF Trust (>2 yrs) 80-160mg BID Initial treatmentshould be nebulized colistin

European Consensus (Doring et al.)

80-160mg QD-BID Max 320mg/day


Colistimethate sodium (CMS)

• Currently not FDA approved• Colistin DPI (Colobreathe ®, Tadim ®) currently

in Europe, United Kingdom, Australia


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Colistimethate sodium powder (Colobreathe®,Tadim®)

Medication Indication Dosage Adverse effects

Colobreathe® >6yrs with P. aeruginosa (FEV1<25%>75%)

1,662,500 IU (125mg CMS) BID via Turbospin® DPI inhaler; Treatment may be continued as long as the physician considers the patient is obtaining benefit

Cough, throat irritation, dyspnea, dysphonia

Tadim® >2yrs with P. aeruginosa (FEV1<25%>75%)

1-2 million IU (80-160mg CMS) neb soln two or three times daily

Chest tightness

CMS EvidenceTrial Treatment Outcomes

Valerius NH et al. 1991n=26 pts

CMS 80mg BID with PO Cipro for 3wk; RPCT

Tx pts were 88% less likely to be colonized with Pseudomonas at 24 mo post tx; clinical outcomes not measured

Taccetti G et al. 2005n=47 pts

CMS 80-160mg BID with PO cipro;

Median time to recolonization 18 mo after eradication; FEV-1 less than in pts with chronic infx (p<0.05)

Frederiksen B et al. 1997n=48

CMS 80mg BID –160mg TID with PO cipro

Tx prevented or delayed chronic infx by 78% over 3.5 yrs (p<0.005)


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CMS Evidence

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Trial Treatment Outcomes

Hodson ME et al. 2002n=115 pts (age 7-50 yrs)

TIS 300 mg BID or CMS 80 mg BID for 4 wks; RCOL,multicenter

Tobramycin (n=53) hadFEV1 compared to colistin (n=62) 6.7% vs. 0.37% (p=0.006); Did not reach target sample size of 60 pts per group

Jensen T et al. 1987n=40 pts (age 7-35 yrs)

CMS 80mg BID; RDBPCT In FVC at 90 days with tx (7 vs 18); no difference in FEV1 btwn groups

Schuster A et al. 2013n=380 (>6yrs)

CMS DPI 125mg BID 24-weeks vs. TIS 300mg BID 28 days on 28 days off for 3 cycles.

No difference in meanchange in FEV1 (-0.56%; 95% CI -2.71-1.70%); Ease of use 91% vs. 54% (p<0.001)

CMS powder Evidence Summary

Yes

• Pts > 6yrs with moderate to severe dx with chronic P. aeruginosa infection for 24-weeks (FEV1<25%>75%)

• >2yrs with moderate to severe dx with chronic P. aeruginosa (FEV1<25%>75%)

Yes?• Pts with early colonization with P. aeruginosa in combo with PO cipro• Only one trial was prospective, randomized, and PC

Future• Showing non-inferiority vs TIS; Need trial comparing CMS DPI vs TIP


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Future Inhaled antibiotics

• Levofloxacin solution (Aeroquin®)• Liposomal Amikacin solution (Arikace®)• Vancomycin powder (AeroVanc®)




Infection

Inflammation

Bronchiectasis


Anti-inflammatoryIbuprofen, Azithromycin, Inhaled corticosteroids


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Anti-inflammatory Therapy

• Ibuprofen– Inhibits cyclooxygenase and lipoxygenase (at high

doses)– Via inhibition of lipooxygenase = migration &

function of neutrophils is ↓– Ages 6-17 years– FEV-1>60% predicted– Use 20-30 mg/kg twice daily– Peak plasma 50-100 mcg/mL

• Draw levels 60, 120,180minutes after taking dose


Anti-inflammatory Therapy• Azithromycin (Macrolide antibiotic)

– Long tissue half life--accumulates in sputum & lungs

• Potent anti-inflammatory– Exact mechanism unknown– Inhibits production of proinflammatory cytokines– Exhibits anti-biofilm effects

• May improve pulmonary function & decrease hospitalizations

Flume P et al. Am J Respir Crit Care Med. 2007;176(10):957-69


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Anti-inflammatory Therapy• Patient selection

– >6 years– Persistent P. aeruginosa (net benefit high)– Without Persistent P. aeruginosa (net benefit moderate)

• Azithromycin Dosing – <18 kg: 10 mg/kg/dose M, W, F– 18-37.5 kg: 250 mg M, W, F– >37.5 kg: 500 mg M, W, F– <40kg: 250mg daily– >40kg: 500mg daily


Anti-inflammatory Evidence Summary

Yes• Ibuprofen 6 and 17 years of age, with an FEV1 > 60% predicted• Azithromycin >6yrs with chronic P. aeruginosa• Azithromycin >6yrs w/o chronic P. aeruginosa

Yes?• Inhaled steroids in pts with asthma or abpa

Future• ?


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Infection

Inflammation

Bronchiectasis


CFTR ModulatorsIvacaftor, lumacaftor/ivacaftor

Ivacaftor (Kalydeco®)• CFTR potentiator for G551D, G178R, S549N,

S549R, G551S, G1244E, S1251N, S1255P,G1349D, and R117H mutations

• Dosage– ≥ 6 yrs: 150 mg (1 tablet) twice daily– 2-6yrs: <14 kg: 50 mg packet twice daily; ≥14 kg: 75 mg

packet twice daily– Reduce dose moderate/severe hepatic impairment

• Increase absorption with high-fat meal– ↑ 2.5 to 4-fold

• Pregnancy category B



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Ivacaftor (Kalydeco®)• Adverse effects

– headache, oropharyngeal pain, upper respiratory tract infection, nasal congestion, abdominal pain, nasopharyngitis, diarrhea, rash, nausea, and dizziness

• Must monitor LFT quarterly 1st year then annual• Ophthalmological exams at baseline and yearly eye

exams (pediatric patients)• Interactions

– CYP3A4 inducers (rifampin)• Avoid concomitant use

– CYP3A4 inhibitors (azole antifungals)• Reduce dose to 150mg twice weekly (ketoconazole)• Reduce dose to 150mg daily (fluconazole)• Avoid grapefruit or Seville oranges

Lumacaftor + Ivacaftor (Orkambi®)

• Homozygous F508del • Dosage (lumacaftor/ivacaftor)

– 6-11yrs: 100 mg/125mg (2 tablets) twice daily• Approved 9/28/16

– ≥ 12 yrs: 200 mg/125mg (2 tablets) twice daily– Reduce dose moderate/severe hepatic impairment

• Increase absorption with high-fat meal– ↑ 2 to 3-fold

• Pregnancy category ?


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• Adverse effects– dyspnea, nasopharyngitis, nausea, diarrhea, upper

respiratory tract infection, fatigue, respiration abnormal, blood creatinine phosphokinase increased, rash, flatulence, rhinorrhea, influenza

• Must monitor LFT quarterly 1st year then annual• Ophthalmological exams at baseline and

yearly eye exams (pediatric patients)


• Interactions– CYP3A4 inducers (rifampin)

• Avoid concomitant use– CYP3A4 inhibitors (azole antifungals)

• Reduce dose to 200/120mg daily x7d then 400/250mg BID (ketoconazole)

• No dosage adjustment is required for patients already maintained on lumacaftor/ivacaftor who begin therapy with a CYP3A inhibitor.

• No dosage adjustment of ivacaftor/lumacaftor with: azithromycin, aztreonam, budesonide, ceftazidime, cetirizine, ciprofloxacin, colistimethate, colistin, dornase alfa, fluticasone, ipratropium, levofloxacin, pancreatin, pancrelipase, salbutamol, salmeterol, sulfamethoxazole and trimethoprim, tiotropium, and tobramycin

• Avoid grapefruit or Seville oranges


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CFTR Modulator Evidence Summary

Yes• >2yrs for G551D, G178R, S549N, S549R, G551S, G1244E, S1251N, S1255P,G1349D,

and R117H mutations• >12yrs for homozygous F508del mutations

Yes?• Ivacaftor >6yrs non-G551D mutations

Future• >2-5yrs ivacaftor PK/PD with >1 gating mutation • 0-2yrs ivacaftor PK/PD with G551D, G178R, S549N, S549R, G551S, G1244E,

S1251N, S1255P, or G1349D.G1349D mutation • >6-11yrs for homozygous F508del mutations w/FEV1 70-105%

Conclusions

• Cystic fibrosis is a genetic disorder that affects multiple organ systems

• The complexity of chronic medications to treat and alleviate symptoms of CF has dramatically increased.

• Pharmacists can play a key role in the management chronic medications in the treatment of patients with cystic fibrosis

objectives - proces3.proce.com/res/pdf/cf/cf2handout.pdf · objectives • discuss current...

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