Cystic Fibrosis

Question 1

CFTR Modulators

Answer 1

Ivacaftor
Lumacaftor / Ivacaftor
Tezacaftor / Ivacaftor
Elexacaftor / Tezacaftor / Ivacaftor

Question 2

Ivacaftor - Role

Answer 2

“potentiator” - facilitates opening of the chloride channel

Question 3

Lumacaftor, Tezacaftor, Elexacaftor - Role

Answer 3

“corrector” - fixes the defective CFTR protein so it can move to the proper place on the airway cell surface

Question 4

Ivacaftor - Mutations

Answer 4

heterozygous F508del (one copy)
or other responsive mutations

Question 5

Ivacaftor - Age Requirement

Answer 5

1 month or older

Question 6

Lumacaftor + Ivacaftor - Mutations

Answer 6

homozygous F508del (two copies)

Question 7

Lumacaftor + Ivacaftor - Age Requirement

Answer 7

1 year or older

Question 8

Tezacaftor + Ivacaftor - Mutations

Answer 8

homozygous F508del (two copies)
or at least 1 other responsive mutation (based on in vitro data)

Question 9

Tezacaftor + Ivacaftor - Age Requirement

Answer 9

6 years or older

Question 10

Elexacaftor + Tezacaftor + Ivacaftor - Mutations

Answer 10

hetero- or homozygous F508del (either one or two copies)
or at least 1 of 175 other approved mutations

Question 11

Elexacaftor + Tezacaftor + Ivacaftor - Age Requirement

Answer 11

2 years or older

Question 12

CFTR Modulators - Adverse Effects

Answer 12

adverse effects: abdominal pain, diarrhea, rash, increased ALT/AST, rhinorrhea, headache

Question 13

CFTR Modulators - LFT Monitoring

Answer 13

monitor LFTs at baseline, every 3 months x 1 year, then yearly
stop if ALT or AST > 5x ULN
or AST > 3x ULN & bilirubin > 2x ULN

Question 14

CFTR Modulators - DDIs

Answer 14

strong CYP3A4 inhibition (clarithromycin, itraconazole)
moderate CYP3A4 inhibition (erythromycin, fluconazole)
CYP3A4 induction (rifampin, carbamazepine, phenobarbital, phenytoin, St. John’s wort)

Question 15

Strong CYP3A4 Inhibitors - CFTR Modulators Dose Adjustment

Answer 15

I - twice weekly
ETI - twice weekly

Question 16

Moderate CYP3A4 Inhibitors - CFTR Modulators Dose Adjustment

Answer 16

I - once daily
ETI - alternate with I every other day

Question 17

CF - Pulmonary Therapies

Answer 17

anti-inflammatory agents
inhaled antibiotics
mucolytic agents / bronchodilators
annual vaccinations (influenza)
physiotherapy

Question 18

Anti-inflammatory Agents

Answer 18

azithromycin
ibuprofen

Question 19

Mucolytic Agents

Answer 19

dornase alfa 2.5 mg QD-BID inhaled
saline 7% BID inhaled (pre-treat with albuterol)

Question 20

Azithromycin - Dose

Answer 20

10 mg/kg MWF, or
250 mg MWF if 18-40 kg
500 mg MWF if 36 kg or more

only in patients 6 and older

Question 21

Inhaled Antibiotics

Answer 21

• TOBI nebulizer 300 mg BID (over 15 min)
• TOBI Podhaler 112 mg BID (over ~5 min)
• Aztreonam 75 mg TID (over 2-3 min; pre-treat with albuterol)

28 days on, 28 days off for all
6 years or older for all

Question 22

Acute Pulmonary Exacerbations - Symptoms

Answer 22

cough
increased sputum production
SOB
chest pain
loss of appetite, weight loss
lung function decline

Question 23

APE - Pulmonary Management

Answer 23

intensify all of the following:
- vest treatment
- dornase alfa
- hypertonic saline
- albuterol (to QID)

Question 24

APE with MSSA and no PA - Antibiotic Choice

Answer 24

penicillin or cephalosporin

Question 25

APE with MSSA and PA - Antibiotic Choice

Answer 25

cefepime + aminoglycoside

Question 26

APE with MRSA and no PA - Antibiotic Choice

Answer 26

vancomycin or linezolid

Question 27

APE with MRSA and PA - Antibiotic Choice

Answer 27

vancomycin or linezolid + aminoglycoside + ceftazadime

Question 28

Aminoglycosides - EID PK Goals

Answer 28

peak 22.5-27.5 mcg/mL
18-hr < 1 mcg/mL
trough < 0.1 mcg/mL (undetectable)
AUC 80-100 mcg/mL x hr

Question 29

Vancomycin - PK Goals

Answer 29

trough 10-20 mcg/mL
AUC / MIC 400 or greater

Question 30

IV Antibiotics - Levels Monitoring

Answer 30

draw serum concentrations initially and every 3-7 days