What are the 10 ADEs of inhaled Aztreonam? (3 were in red)
1. *Fever (MC in children)
4. Nasal congestion
5. Pharyngeal pain
8. Chest discomfort
9. Abd pain
Do not repeat aztreonam ______ days after completion
(to provide continuous coverage: could do 28d Aztreonam then 28d Tobramycin then 28d Aztreonam....)
The following is the mechanism of which drug?
–Reversibly inhibits cyclooxygenase-1 and 2 (COX-1 and 2) enzymes
–decreased formation of prostaglandin precursors
What is the minimum age that you can give ibuprofen?
must be > 6 months
Which patients is high-dose ibuprofen indicated for?
Patients under 18y/o w/ FEV >60%
(insufficient evidence for ppl under 18y/o)
•Less decline in pulmonary function
•Able to maintain weight and had less hospital admissions
•Benefits exceed the risks of GI complications and nephrotoxicity
•< 5% of CF patients on this regimen
What are requirements to obtain a specific therapeutic level of ibuprofen?
Frequent blood draws for pharmacokinetic monitoring
- Target peak plasma concentration between 50-100 μg/ml
What are the 6 main ADEs of Ibuprofen?
3. *Fluid retention
4. *Epigastric pain
5. *GI bleed
(also dyspepsia and flatulance can occur)
Interactions of which CFTR modulator?
–Substrate of CYP3A4 (major);
–Inhibits CYP2C8 (weak), CYP2C9 (weak), CYP3A4 (weak), P-glycoprotein
The following are the main ADEs of which med?
- *Abdominal pain
- *Transaminases increased
(a CFTR modulator)
MOA of which med?
–Potentiates epithelial cell chloride ion transport of defective (G551D mutant) cell-surface CFTR protein
–improves regulation of salt and water absorption and secretion in various tissues (eg, lung, gastrointestinal tract).
(a CFTR modulator)
What is the con of Ivacaftor?
Very expensive (~300,000/year)
MOA of the combination of which 2 drugs?
- F508del mutation interferes with CFTR protein folding and channel gating activity
- partially corrects the CFTR misfolding
- Improves the gating abnormality
People w/ 2 copies of the ______ mutation represent the largest group of people w/ CF
Data from 2 phase III studies on people w/ 2 copies of the F508del mutation showed statistically significant improvements in lung function when pts were treated with what?
Data from 2 phase III studies on people w/ 2 copies of the F508del mutation showed that patients who took Lumacaftor/ivacaftor also experienced reductions in _____ and improvements in _______*
(in addition to improvements in lung function)
*reductions in pulmonary exacerbations*
*Improvements in BMI*
>10% of people taking Lumacaftor/Ivacaftor experience what main ADE? (the only red one)
(Also nausea, diarrhea, chest discomfort and dyspnea)
What are the 6 main ADEs of Lumacaftor/Ivacaftor? (the ones in red)
3. Menstrual disease (amenorrhea, dysmennorhea, etc)
4. Increased creatinine phosphokinase
Tezacaftor/Ivacaftor is combination therapy used to tx CF.... What is Tezacaftor designed to do?
Tezacaftor is designed to move the defective CFTR protein to the proper place in the airway cell surface (similar to Lumacaftor)
Tezacaftor/Ivacaftor is combination therapy used to tx CF.... What is Ivacaftor designed to do?
Ivacaftor helps facilitate the opening of the chloride channel on the cell surface to allow chloride and sodium (salt) to move in and out of the cell
Who is Tezacaftor/Ivacaftor combination therapy approved for? (2 different types of individuals)
- individuals >12y/o with 2 copies of 508del (MC CF mutation)
- individuals who have a single copy of one of 26 specified mutations -- regardless of their other mutation
Tezacaftor/Ivacaftor (Symdeko) should be taken with what type of food?
The dose of Tezacaftor/Ivacaftor should be reduced in patients with moderate and severe _______
The dose of Tezacaftor/Ivacaftor should be reduced when it is co-administered with drugs that are moderate or strong _______ inhibitors
Concomitant use of Tezacaftor/Ivacaftor with strong CYP3A inducers (e.g., rifampin, St. John’s wort) may substantially decrease the therapeutic effectiveness of __________thus co-administration is not recommended
Avoid food containing grapefruit or Seville oranges when giving what med?
What are the 4 common adverse drug rxns of Tezacaftor/Ivacaftor?
3. Sinus Congestion
"Some Headaches Never Die"
How should you monitor a patient on Tezacaftor/Ivacaftor?
ALT and AST prior to initiating treatment and every 3 months during the first year of treatment, annually thereafter
Monitoring parameters for Tezacaftor/Ivacaftor:
When should you discontinue treatment?
If significant elevations of transaminases
(ALT or AST >5 x upper limit of normal (ULN), or ALT or AST >3 x ULN with bilirubin >2 x ULN)
Why is baseline and follow-up examinations recommended in pediatric patients prior to initiating treatment with Tezacaftor/Ivacaftor?
Cataracts: Non-congenital lens opacities/cataracts have been reported in pediatric patients
Which 2 vaccines should be given to patients with CF?
1. influenza vaccine (anyone older than 6mo)**
2. Pneumococcal vaccine**
The following describes which recommended vaccine for patients w/ CF?
- Monoclonal antibody against respiratory syncytial virus
- Children younger than 24 months of age
- Not a firm recommendation
When should a CF patient be given oxygen and BiPAP?
Oxygen: progressive CF accompanied by worsening hypoxemia
BiPAP: advanced CF and hypercapnia
According to the International Society for Heart and Lung Transplantation, when should a pt be referred to a transplant center? (4 things)
FEV <30% predicted or a rapid decline in FEV1, particularly in young female patients
- Increasing freq. of exacerbations requiring abx
- Refractory/recurrent pneumothorax
- Recurrent hemoptysis not controlled by emobilization
What 4 GI treatments are used in CF?
Pancreatic enzyme supplementation
- Prevention and tx of cirrhosis
What disease is 6-8x more common in CF children than those w/o CF? How do you tx this?
- Proton Pump Inhibitors
Which group of meds?
–act by irreversibly blocking the hydrogen/potassium adenosine triphosphatase enzyme system (the H+/K+ ATPase, or more commonly, the gastric proton pump) of the gastric parietal cells.
–The proton pump is the terminal stage in gastric acid secretion, being directly responsible for secreting H+ ions into the gastric lumen.
Proton Pump Inhibitors
The following are apart of which group of meds and what do they treat? ("-prazole")
Proton Pump Inhibitors
Used to tx GERD
What are the 5 main ADEs of Omeprazole? (the ones in red)
1. Acid regurgitation
3. Back pain
What is the "backbone of GI therapy" in patients w/ CF?
pancreatic enzyme supplementation
Dosage of Pancreatic enzyme supplementation is calculated using ______ units
ADEs of pancreatic enzyme supplementation:
Prolonged contact of the enzyme supplements with oral mucosa may cause ______, especially with the powdered form
–Administer with food (eg, applesauce), even in infants*
–Mouth should be rinsed after administration, particularly in infants*
Pancreatic Enzyme Supplementation
*Excessive doses of pancreatic enzymes can cause what?*
(characterized by inflammation and strictures)**
(risk reduced by limiting dose to < 2500 lipase units/kg)
- Pancreatic insufficiency and CF related liver dz lead to ____ _______
- This predisposes to what?
- Fat malabsorption
- predisposes to deficiencies (Vitamins A, D, E, K)
Decreased calcium absorption and intake in CF can lead to what?
Dosing of Vitamin A, D, E, and K supplementation is based on what?
The following describes what med, which is used to tx CF- related liver disease:
–Decreases the cholesterol content of bile and bile stones
–Mechanism is reduction of the secretion of cholesterol from the liver and the fractional reabsorption of cholesterol by the intestines
Gallstone dissolution agent
What are the 4 main ADEs of Ursodeoxycholic acid (Gallstone dissolution agent)
(the ones that are blue on the slide)
4. Serum creatinine increased