Cystic Fibrooooo Flashcards
How old do you have to be to use ivacaftor?
older than 1 month
How old do you have to be to use Lumacaftor-Ivacaftor
Older than 1 year
How old do you have to be to use tezacaftor/ivacaftor
older than 6 years
How old do you have to be to use elexacaftor/tezacaftor/ivacaftor
Older than 2 years
Mutation that can use ivacaftor
ivacaftor-responsive CFTR mutation (G551D) - I think we get this chart on the exam??
Mutation that can use lumacaftor/ivacaftor
2 copies of the F508 del CFTR mutation (homozygous)
Mutation that can use tezacaftor/ivacaftor
2 copies of the F508 del CFTR mutation (homozygous)
OR
> 1 CFTR mutation that is reponsive to T-I
Mutation that can use elexacaftor/tezacaftor/ivacaftor
Everyone :)
ivacaftor MOA
- Facilitate opening of the Cl channel (CFTR potentiator)
- Does NOT create more protein, helps existing proteins work better
lumacaftor MOA
fixes defective CFTR protein so that it can move to the proper place on the airway cell surface (CFTR corrector)
tezacaftor MOA
fixes defective CFTR protein so that it can move to the proper place on the airway cell surface (CFTR corrector)
CFTR modulator agents
-caftor
CFTR modulator monitoring
- AST/ALT Q3mo. for the first year and then annualy after
- Need dose adjustment if liver impairment
CFTR admin
- Give with fat containing meal to boost absoprtion
- NO GRAPEFRUIT
Dornase alfa in CF
- Breaks up secretions
- Improves pulmonary function and reduce acute pulmonary exacerbations
- Well tolerated
Hypertonic salinein CF
- Doesn’t improve lung function but does reduce times that pateint gets sick
- Well tolerated, but some bronchospasm reported as AE
Bronchodilator use in CF
- Really only used because some of the other meds can cause bronchospasms (e.g. hypertonic saline
- Albuterol is the most used agent
anti-inflammatory agent in CF
Azithromycin - not being used as an ABX
- Dosed MWF
- If pt <25kg: 10mg/kg
- If pt <40kg: 250mg
- If pt >40kg: 500mg
Azithromycin indication in CF?
most clear indication for patients w PA colonization
Can be used w/o PA if hx of frequent APEs
CF non-pharm and supplements
- Flu vaccine
- Physiotherapy
- Vitamins: A, D, E, K
- Pancreatic enzyme replacement (PERT) - microencapsulated products
- dose dependent on lipase component - Fe
- Zinc if poor weight gain
CF inhaled ABX
- Tobramycin
- Nebulizer admined over 15min
- DPI admined over 2-7 min
- Aztreonam
- Nebulizer admined over 2-3 min
- Use ABX alternating 28 days ON and 28 days OFF → reduce resistnace
S/S of acute CF pulmonary exacerbation
- Cough, Increased sputum production
- SOB
- Chest pain
- Loss of appetite, Weight loss
- Lung function decline
CF exacerbation admission: what to do with homes meds
basically double frequency
- Increase vest treatment frequency
- Increase dornase alfa frequency
- Infrease hypertonic saline frequency
- Increase bronchodilator frequency
doubleitandgiveittothenextperson
CF exacerbation admission: ABX monitoring
- S/S persistence and/or resolution
- Pulmonary function tests: FEV1 and FVC
- Sputum culture and susceptibilities
- BUN/SCr
- ABX serum [ ]
if no improvement in 5-7 days, re-culture and/or adjust ABX (
CF exacerbation: MSSA infection ABX options
anti-staph penicillin OR cephalosporin 10-14D
CF exacerbation: MSSA and PA infection ABX options
Aminoglycoside AND cefepime 10-14D
CF exacerbation: MRSA infection ABX options
Vanco or linezolid 10-14D
CF exacerbation: MRSA and PA infection ABX options
- vanco or linezolid +
- aminoglycoside +
- beta-lactam (ceftazidime)
for 10-14D
Aminoglycoside goal [ ]
- Traditional
- Goal peak: 10-12 mcg/ml
- Goal trough: <1.5 mcg/ml
- Extended interval
- Goal peak: 22.5-27.5 mcg/ml
- Goal 18hr: <1mcg/ml
- AUC 80-100 mcg/ml*hr
Vanco goal [ ]
- Goal trough: 10-20 mcg/mL (→ AUC/MIC >400)
- Serum concentrations drawn initially and then every 3 – 7d
CFTR modulator AE
Generally well tolerated, but….
- abdominal pain
- diarrhea
- rash
- rhinorrhea
- headache
- elevated ALT/AST
How is ivacaftor dosed?
- BID
- strength dependent on age and weight
How is lumacaftor/ivacaftor dosed
- combo tab BID
- strength dependent on age and weight
How is tezacaftor/ivacaftor dosed
- combo tab in AM, ivacaftor tab in PM
- strength dependent on age and weight
How is elexacaftor/tezacaftor/ivacaftor dosed?
- combo tab in AM and ivacaftor in PM
- strength dependent on age and weight
CFTR modulator DDI with moderate CYP3A4 inhibitors
erythromycin and fluconazole
- iva: decrease to QD
- teza or tri: combo and iva taken on alternating days
CFTR modulator DDI with strong CYP3A4 inhibitors
clarithromycin and itraconazole
- iva: decrease to twice weekly
- teza or tri: decrease to twice weekly
- luma: decrease dose to 1 tab QD for 1 week then return back to BID (only if luma is being added to strong CYP3A4, not if CYP3A4 being added to luma
CFTR modulator DDI with CYP3A4 inducers
rifampi, CBZ, phenobarbital, phenytoin, St. John
- avoid CFTR use
When to use ETI
First line, whenever applicable in whoever can
When to use TI
In patients who have the appropriate mutation, can’t use ETI and are over 6
When to use iva
if pt < 2 years but greater than 1 month old and has appropriate mutation; switch to ETI when they turn 2
When to use LI
if pt < 2 years but greater than 1 year and is F508delta homo
* switch to ETI when they turn 2
Important equations for CF ABX
there’s 3: Ke, C, and T1/2
- Ke = ln(C1/C2) / ∆t
- C = C0 (e^-kt)
- T1/2 = 0.693/ Ke
AGS peak is 1 hr post infusion
The patient develops an erythematous, pruritic rash on her face, neck, and upper torso, during
vancomycin infusion. What is it?
AnaphyLACTOID reaction - vanco flushing syndrome (mast cell mediated but not hypersensitivity)
How to treat vanco anaphylactoid reaction?
Step 1: Stop vancomycin infusion
Step 2: Order diphenhydramine +/- H2RA +/- IV fluids (if patient hypotensive)
Most episodes will resolve within 20 minutes, and the vancomycin may be restarted at 50% of the original rate (mild cases)
What do you do if Scr increases 50% while on abx therapy for APE?
Check tobramycin 18-hour level and vancomycin trough prior to next dose.
Hold doses pending level assessment.
