Cystic Fibrosis Flashcards
CFTR Modulators
Ivacaftor
Lumacaftor / Ivacaftor
Tezacaftor / Ivacaftor
Elexacaftor / Tezacaftor / Ivacaftor
Ivacaftor - Role
“potentiator” - facilitates opening of the chloride channel
Lumacaftor, Tezacaftor, Elexacaftor - Role
“corrector” - fixes the defective CFTR protein so it can move to the proper place on the airway cell surface
Ivacaftor - Mutations
heterozygous F508del (one copy)
or other responsive mutations
Ivacaftor - Age Requirement
1 month or older
Lumacaftor + Ivacaftor - Mutations
homozygous F508del (two copies)
Lumacaftor + Ivacaftor - Age Requirement
1 year or older
Tezacaftor + Ivacaftor - Mutations
homozygous F508del (two copies)
or at least 1 other responsive mutation (based on in vitro data)
Tezacaftor + Ivacaftor - Age Requirement
6 years or older
Elexacaftor + Tezacaftor + Ivacaftor - Mutations
hetero- or homozygous F508del (either one or two copies)
or at least 1 of 175 other approved mutations
Elexacaftor + Tezacaftor + Ivacaftor - Age Requirement
2 years or older
CFTR Modulators - Adverse Effects
adverse effects: abdominal pain, diarrhea, rash, increased ALT/AST, rhinorrhea, headache
CFTR Modulators - LFT Monitoring
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
CFTR Modulators - DDIs
strong CYP3A4 inhibition (clarithromycin, itraconazole)
moderate CYP3A4 inhibition (erythromycin, fluconazole)
CYP3A4 induction (rifampin, carbamazepine, phenobarbital, phenytoin, St. John’s wort)
Strong CYP3A4 Inhibitors - CFTR Modulators Dose Adjustment
I - twice weekly
ETI - twice weekly
Moderate CYP3A4 Inhibitors - CFTR Modulators Dose Adjustment
I - once daily
ETI - alternate with I every other day
CF - Pulmonary Therapies
anti-inflammatory agents
inhaled antibiotics
mucolytic agents / bronchodilators
annual vaccinations (influenza)
physiotherapy
Anti-inflammatory Agents
azithromycin
ibuprofen
Mucolytic Agents
dornase alfa 2.5 mg QD-BID inhaled
saline 7% BID inhaled (pre-treat with albuterol)
Azithromycin - Dose
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
Inhaled Antibiotics
- 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
Acute Pulmonary Exacerbations - Symptoms
cough
increased sputum production
SOB
chest pain
loss of appetite, weight loss
lung function decline
APE - Pulmonary Management
intensify all of the following:
- vest treatment
- dornase alfa
- hypertonic saline
- albuterol (to QID)
APE with MSSA and no PA - Antibiotic Choice
penicillin or cephalosporin
APE with MSSA and PA - Antibiotic Choice
cefepime + aminoglycoside
APE with MRSA and no PA - Antibiotic Choice
vancomycin or linezolid
APE with MRSA and PA - Antibiotic Choice
vancomycin or linezolid + aminoglycoside + ceftazadime
Aminoglycosides - EID PK Goals
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
Vancomycin - PK Goals
trough 10-20 mcg/mL
AUC / MIC 400 or greater
IV Antibiotics - Levels Monitoring
draw serum concentrations initially and every 3-7 days