Cystic Fibrosis

Question 1

What must you ALWAYS check before prescribing something to a CF patient??

Answer 1

Drug Allergies!

Question 2

What is the most common CFTR mutation?

Answer 2

F508delta

Question 3

What are some comorbidities that come with CF? (5)

Answer 3

Depression/anxiety
Asthma
Acid reflux
CF-related diabetes
Sinus disease

Question 4

What is the minimum age to use Ivacaftor?

Answer 4

1 month

Question 5

What is the minimum age to use Lumacaftor/ivacaftor?

Answer 5

1 year

Question 6

What is the minimum age to use elexacaftor/tezacaftor/ivacaftor (Trikafta)?

Answer 6

2 years

Question 7

What is the minimum age to use Tezacaftor/Ivacaftor?

Answer 7

6 years

Question 8

Ivacaftor - usable mutations

Answer 8

G551D**
HETEROZYGOUS F508delta
R117H, G1244E, G1349D, G178R, G551S, S1251N, S1255P, S549N, S549R

Question 9

What mutation is Lumakaftor/Ivacaftor indicated for?

Answer 9

F508delta HOMOZYGOUS mutation

Question 10

What mutations are indicated for Tezacaftor/Ivacaftor?

Answer 10

F508delta homozygous
OR
≥1 responsive mutuation (same as Trikafta)

Question 11

What mutations are indicated for Trikafta?

Answer 11

≥ 1 copy of F508delta
OR
One of >175 other mutations
(Pretty much anyone can use)

Question 12

What are some AEs of CFTR modulators?

Answer 12

INCREASED AST/ALT
Abdominal pain
Diarrhea
Rash
Increased blood creative phosphokinase
Rhinorrhea
HA

Question 13

What is the main monitoring parameter for CFTR modulators?

Answer 13

Liver transaminases & bilirubin every 3 months for the first year then every year

Question 14

What two factors affect CFTR dosing?

Answer 14

Age
Weight

Question 15

What are moderate CYP3A4 inhibitors (2) and how would you change T/I or E/T/I dosing?

Answer 15

Moderate inhibitors:
- Erythromycin
- Fluconazole

Alternate every OTHER day with just Ivacaftor

Question 16

What are strong CYP3A4 inhibitors (2) and how would you change Ivacaftor, T/I, E/T/I dosing?

Answer 16

Strong CYP3A4 inhibitors:
- Clarithromycin
- Itraconazole

Adjust to TWICE PER WEEK dosing

Question 17

What are CYP3A4 inducers (5) and how would you change Ivacaftor, T/I, E/T/I dosing?

Answer 17

Inducers:
- Rifampin
- Carbamazepine
- Phenobarbital
- Phenytoin
- St. John’s Wort
(Mostly antiepileptics)

AVOID CFTR modulator use!

Question 18

Patient ZB has just turned 1 year old and has been on ivacaftor since he was 2 months old. What is the next step for treatment with CFTR modulators?

Answer 18

Keep using ivacaftor then switch to Trikafta (E-T-I) once he turns 2 years old.

Question 19

Which vaccine is recommended to CF patients?

Answer 19

Influenza, starting at 6 months

Question 20

What non-pharmacologic therapy can be used for mucolysis?

Answer 20

High frequency chest wall oscillation (HFCWO)
Aka “vest” therapy

Question 21

What bronchodilators should you use in CF? When would you use them?

Answer 21

Only SABAs recommended

Used in:
- asthmatic CF patients
- improve deposition of inhaled meds
- if other medications cause bronchospasm, use PRN

Question 22

What TWO topical mucolytic/hydrating agents are there for CF patients?

Answer 22

Dornase alpha = 2.5 mg inhaled 1-2 times daily
Improves FEV1, Decreases rate of APEs
AEs: vocal hoarseness, rash

Hypertonic Saline = 7% inhaled BID
May pretreat w/ albuterol
Only decrease in APEs
AEs: bronchospasms

Question 23

Who should use azithromycin (3x weekly)?

Answer 23

Patients ≥6 years with chronic pseudomonas
Patients ≥6 years WITHOUT Pseudomonas (consider!)

Question 24

What are some AEs of using azithromycin?

Answer 24

Nausea
Diarrhea
Wheezing
ABX resistance?? -> not really a concern

Question 25

What inhaled antibiotics could be considered in those with pseudomonas? What is the timeline for administration?

Answer 25

Tobramycin (TOBI podhaler or nebulized soln) - BID - Podhaler preferred d/t rapid administration - increased FEV, decreased APEs Aztreonam nebulized soln - TID - Increased FEV only Both are 28 days ON and 28 days OFF

Question 26

What are AEs of tobramycin and aztreonam inhaled abx?

Answer 26

Tobra AEs - voice alteration, tinnitus Aztreonam AEs - bronchospasms (pretreat w/ SABA)

Question 27

What are symptoms of APEs?

Answer 27

SOB Increased sputum production Loss of appetite Lung function decline Cough Chest Pain

Question 28

If a patient is having an APE, how do you alter their current pulmonary treatment regimen?

Answer 28

DOUBLE the FREQUENCY of all! Vest treatment Dornase alpha Hypertonic saline SABA

Question 29

What abx do you use in CF APE with... - MSSA + no pseudomonas? - MSSA + pseudomonas? - MRSA + no pseudomonas? -MRSA + pseudomonas?

Answer 29

MSSA + no PA = Penecillin/Cephalosporin MSSA + PA = Cefepime + Tobramycin (aminoglycoside) MRSA + no PA = Vancomycin or Linezolid MRSA + PA = Vancomycin or Linezolid AND Ceftazidime (beta-lactam) + Tobramycin (aminoglycoside)

Question 30

What are two dosing strategies for abx in APEs to improve efficacy?

Answer 30

Extended interval aminoglycoside dosing Continuous beta-lactam infusion

Question 31

What is the duration of abx used in APEs?

Answer 31

10-14 days No improvement in 5-7 days, adjust

Question 32

What should be monitored when using abx for APEs? (4)

Answer 32

Monitor: - Sx persistence & resolution - FEV, FVC - Sputum dx and ABX susceptibilities - BUN, SCr

Question 33

What are the goal peaks and troughs of… - traditional aminoglycoside dosing? -Extended-interval aminoglycoside dosing?

Answer 33

Traditional: Peak - 10-12 mcg/mL Trough - <1.5 mcg/mL Extended: Peak - 22.5-27.5 mcg/mL @ 18hr - <1 mcg/mL Trough - <0.1 mcg/mL

Question 34

What is the goal trough of vancomycin?

Answer 34

10-20 mcg/mL Draw every 3-7 days