Download medication guidelines for pediatric patients with cystic fibrosis

Medication Guidelines for Pediatric Cystic Fibrosis Patients
Cameron Jordan, PharmD, BCPS
Pediatric Pharmacy Satellite Hours: 07:00-23:30
Pediatric Pharmacy #: 984-974-6679
Blue Team Pharmacist Pager #: 123-7108
After 23:30, call Central Pharmacy for questions: 984-974-8761
Oral Antibiotics
Drug
Dosing
Maximum
single dose
2000 mg
Amoxicillin/
clavulanic acid
15 mg/kg TID
(standard dose) or 45
mg/kg BID (high dose)
Cefpodoxime
5 mg/kg BID
200 mg
Cefuroxime axetil
10-15 mg/kg BID
(suspension) or
250-500mg BID (tablet)
500 mg
Cephalexin
25 mg/kg QID
1000 mg
Ciprofloxacin
20 mg/kg BID
1000 mg
Clarithromycin
15 mg/kg/day divided
BID
500 mg
Clindamycin
600 mg
Dicloxacillin2
30-40 mg/kg/day
divided TID
6.25-12.5mg/kg QID
Doxycycline
1-2 mg/kg BID
100 mg
Levofloxacin
< 5 yo: 10 mg/kg BID
> 5 yo: 10 mg/kg daily
750 mg
250mg*, 500mg*, 750mg tablets*
25mg/mL solution*
Linezolid
< 12 yo: 10 mg/kg Q8
> 12yo: 10 mg/kg Q12
600 mg
600mg tablet*
100mg/5mL suspension*
Minocycline
4 mg/kg once, then 2
mg/kg Q12
100 mg
50mg*, 75mg*, 100mg capsules*
Sulfamethoxazole/
Trimethoprim
(SMX/TMP)
4-6 mg TMP/kg Q12
160mg TMP
80 mg TMP+400 mg SMX tab* 160
mg TMP+800 mg SMX DS tab*
40mg TMP+200mg SMX/5mL
suspension*
500 mg
Available preparations
Other considerations
500mg*, 875mg tablets*
200mg*, 400mg chewables*
XR tablets 1000mg
200mg/5mL*, 400 mg/5mL
suspension*
ES suspension: 600 mg/5mL (less
clavulanic acid)
100mg, 200mg tablets
50mg/5mL, 100mg/5mL
suspension
125mg*, 250mg*, 500mg tablets*
125mg/5mL, 250mg/5mL
suspension
600mg/5mL for high
dose only
250*, 500mg capsules*
125mg/5mL*, 250mg/5mL
suspension*
100mg, 250mg*, 500mg*, 750mg
tablets*
100 mg/mL*, 250mg/5mL
suspension
500mg, 1000mg XR tablets
250mg*, 500mg tablets*
500mg XR tablets
125mg/5mL*, 250mg/5mL
suspension*
75mg, 150mg*, 300mg capsules
75mg/5mL suspension*
125mg*, 250mg*, 500mg
capsules*
50mg*, 100mg capsules*
25mg/5mL suspension*
Suspension and tablet
are not interchangable
Suspension must be
administered with food
Do not give oral
suspension via G-tube or
NG tube
Hold tube feeds 1 hr
before and 2 hrs after
administration
Avoid within 2hrs of
antacids, Ca, Fe, Mg, and
cholestyramine
Suspension should be
administered 1 hr before
or 2hrs after eating
Consider continuing q8
hour dosing if > 12 yr
but less than 45 kg
Avoid within 2hrs of
antacids, Ca, Fe, Mg, and
cholestyramine
*Indicates UNC formulary item
1
Intravenous Antibiotics



Double-cover Pseudomonas, do not combine anti-pseudomonal beta lactams, as they can be antagonistic
Initial doses for Tobramycin and Amikacin should be based on patients’ previous doses; see pharmacist consult note
for past dosing information
If patient has not received aminoglycosides in the past, use the following guide for dosing
Drug
Amikacin
Dosing
15 mg/kg Q12
Maximum single dose
Aztreonam1,2
Cefepime1,3
50-75 mg/kg Q6
50 mg/kg Q8
8-12 g/day
2000 mg
Ceftaroline4
< 6 months: 8 mg/kg Q8
> 6 months and <33 kg:
12 mg/kg Q8
> 33 kg: 400 mg Q8
200-400 mg/kg/day
divided Q6-8
50-100 mg/kg Q12
75 mg/kg Q8
10 mg/kg Q8
10-13.3 mg/kg Q8
3-5 mg/kg/day divided
Q8
25 mg/kg Q6
400 mg
< 5 yo: 10 mg/kg Q12
> 5 yo: 10 mg/kg daily
< 12 yo: 10 mg/kg Q8
≥ 12 yo: 10 mg/kg Q12
750 mg
40 mg/kg Q8
50 mg/kg Q6
100 mg/kg Q6 (based on
piperacillin component)
10 mg/kg Q24 or
previous total daily dose
6mg Q12
2000 mg
2000 mg
4000mg piperacillin
(4.5g Zosyn®)
15-20 mg/kg Q6-8
2000 mg
Ceftazidime1,3
Ceftriaxone
Cefuroxime
Ciprofloxacin1,5
Clindamycin
Colistin1,6
Imipenem/
Cilastatin1,2
Levofloxacin1,5
Linezolid
Meropenem1,2
Oxacillin1
Piperacillin/
Tazobactam1,3
Tobramycin
(extended interval)
Tobramycin
(traditional dosing)
Vancomycin10
Other considerations
Draw peak and trough with 3rd
dose
May require 50 mg/kg Q6 for
Pseudomonas MIC > 161
8-12 g/day
2000 mg
1500 mg
400 mg
2700 mg/day
100mg
Monitor renal function closely
Can use up to 8 mg/kg/day
1000 mg
600 mg
Consider continuing q 8 hour
dosing if > 12 yr but less than
45 kg
Draw levels at 2 and 8 hours
after 1st or 2nd dose started
Draw peak and trough with 3rd
dose
Draw trough prior to 4th dose
2
Nontuberculous Mycobacterium – Antibiotics
*Typically start only one drug each day to assess for nausea/vomiting from each drug
Recommended Regimens (vary by physician preference):
1. Clarithromycin or azithromycin
2. Amikacin
3. Cefoxitin, imipenem/cilastatin, tigecycline, or linezolid
Drug
Amikacin12
Dosing
15 mg/kg IV daily
Maximum single dose
Azithromycin12
5 mg/kg PO daily
Cefoxitin12
200 mg/kg/day divided
TID-QID
15 mg/kg PO BID
20-25 mg/kg IV Q6
250mg (<40kg), 500mg
(> 40 kg)
2g
Clarithromycin12
Imipenem/
cilastatin12
Linezolid12
Tigecycline12,13
< 12 yo: 10 mg/kg Q8
≥ 12 yo: 10 mg/kg Q12
< 10 yo: 1.2 mg/kg IV Q12
> 10 yo: 50mg IV daily
500mg
500mg
600mg
Other considerations
Draw peak and trough with 3rd
dose; goal peak = 20-30 mg/L
Can utilize TID dosing for
home convenience
Can consolidate to Q8 dosing
for home
1:1 PO to IV conversion
50mg
Synergy for Staphylococcus aureus:
Rifampin: 10 mg/kg/dose PO q 12 hours (max dose 600 mg daily for adults)
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Antifungals
*These have lots of drug interactions!
Drug
Dosing
Fluconazole
12 mg/kg x 1, then 6-12
mg/kg IV/PO Q24
Itraconazole
5 mg/kg PO Q12
Voriconazole (IV)
Loading doses:
< 12 yo: 9 mg/kg IV Q12 x 2
doses
> 12 yo: 6 mg/kg IV Q12 x 2
doses
Maintenance doses:
< 12 yo: 5-7 mg/kg IV Q12
> 12 yo: 4 mg/kg IV Q12
9 mg/kg PO Q12
Voriconazole (PO)
Posaconazole19
Maximum
single dose
800mg
200 mg
Suspension: 3-4 mg/kg QID
Tablets: 300mg PO BID x 1
day, then 300mg daily
IV: 300mg IV BID x 1 day,
then 300mg daily
Suspension:
400mg
Available oral preparations
50mg*, 100mg*, 150mg*, 200
mg tablets*
50mg/5mL*, 200mg/5mL
suspension
100mg capsules*
50mg/5mL solution*
50mg*, 200mg tablets*
40mg/mL suspension*
40mg/mL suspension*
100mg DR tablet*
Considerations for antifungal therapies:
Fluconazole
Itraconazole
Posaconazole
Voriconazole
Renally Dose
Adjust
Yes
No
No
No, but do not use IV
formulation if CrCl<50
Drug
Interactions
PPIs: May decrease
fluconazole levels
May increase tacrolimus
levels
Capsules: food increases
absorption
PPIs: May decrease
itraconazole levels
May increase tacrolimus
levels
Capsules: food increases
absorption
PPIs: May decrease
posaconazole levels
May increase tacrolimus
levels
Best absorption with a highfat meal
PPIs: May increase
voriconazole levels
May increase tacrolimus levels
Solution: food decreases
absorption. Take on empty
stomach
Day 5 of therapy
Solution: food decreases
absorption. Take on empty
stomach
Day 14 of therapy
Meals
Steady State
Food may decrease
voriconazole absorption
Give 1 hour before or 1 hour
after a meal
Day 5 of therapy
Day 5 – 7 of therapy in the
absence of a loading dose
Goal Trough
Concentrations
(30 min prior
to dose)
N/A
Itraconazole +
hydroxyitraconazole
> 1 and < 10 mcg/mL
> 700 ng/mL
Day 2 of therapy following a
loading dose
1 – 5.5 mcg/mL
Recommend
Adjustments
N/A
< 1 mcg/mL – increase dose
by 50%
< 700 mg/mL – increase
dose by 50%
< 1 mcg/mL – increase dose by
50%
> 10 mcg/mL – decrease
dose by 25-50%
> 5.5 mcg/mL – decrease dose
by 25-50% (may consider
alternative agents if clinically
significant toxicities)
4
Pharmacokinetic Monitoring for Aminoglycosides and Vancomycin
Peaks and troughs of aminoglycosides are monitored for efficacy and safety, beginning with the 3rd or 4th dose.
For traditional dosing, the trough is drawn immediately before a dose, the dose is given and followed by a flush, and
the peak is drawn 2 hours after hanging the dose. All peaks and troughs must be obtained via peripheral sticks
unless otherwise discussed with pulmonary service.
For extended interval dosing, timed tobramycin levels are drawn at 2 hours and 8 hours after the 1st or 2nd dose is
started. The service pharmacist will use these to extrapolate peak and trough concentrations.
Desired parameters are as follows:
Tobramycin (traditional): trough < 1 mg/dL; extrapolated peak 12-15 mg/dL
Tobramycin (extended interval): trough < 1 mg/dL; extrapolated peak 20-30 mg/dL
Amikacin (for Mycobacterium abscessus): trough < 5 mg/dL; extrapolated peak 20-30 mg/dL
Amikacin (other indications): trough < 5 mg/dL; extrapolated peak 35-45 mg/dL
Usually monitor troughs only for Vancomycin. Trough is drawn immediately before the fourth dose is due. Desired
parameters are:
Vancomycin: trough 15-20 mg/dL
BUN/SCr should be obtained twice weekly. Ensure adequate hydration and discontinue all other nephrotoxic drugs
(including ibuprofen at any dose). Patients should also receive an annual hearing evaluation to evaluate for
ototoxicity from aminoglycosides.
If on vancomycin + aminoglycoside, consider obtaining BUN/SCr more frequently.
Nebulized Medications
Albuterol: 2.5-5 mg nebulized QID
Hypertonic Saline: to transition patient to 7%
3% Hypertonic Saline: 5mL nebulized BID-QID
5.45% Hypertonic Saline: 4mL nebulized BID-QID
1mL 0.9% Sodium Chloride + 3mL 7% Sodium Chloride
7% Hypertonic Saline: 4mL nebulized BID-QID
Dornase Alfa (Pulmozyme®): 2.5mg/2.5mL ampule nebulized daily-BID
Use with PARI® LC + nebulizer
Nebulized antibiotics are administered via nebulizer after the patient’s usual inhaled treatments (including
bronchodilators and dornase) and chest physiotherapy.
Amikacin: Doses vary based on patient tolerance (outpatient therapy only)
250 mg nebulized BID, if tolerated can increase to 500 mg nebulized BID
Aztreonam: 75 mg nebulized TID
Patients must supply own medication, Altera device, and cleaning supplies for inpatient use
Colistin: Doses vary based on patient tolerance
< 6 years: 75 mg nebulized BID
> 6 years: 150 mg nebulized BID
Tobramycin: 300 mg nebulized BID
Vancomycin: 250 mg nebulized BID (outpatient therapy only)
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Other CF Therapies
Pancreatic Enzyme Supplements: Use patient’s home brand, OK to use home meds if not available at UNC.
Infants: Initiate therapy with 1 capsule of Pancreaze 4,200 or equivalent mixed with one teaspoon of
applesauce at beginning of feed. Do not place enzymes in baby bottles. Usual doses: 1500-2500 units
lipase/kg/feed.
Children: Initiate therapy with 500-2000 units lipase/kg/meal. Usual doses are 10,000-15,000 units
lipase/kg/day.
Goals: Adjust doses based on degree of steatorrhea and stool frequency: 3-4 stools/day for infants; 1-2
stools/day for children and adolescents. If enzyme requirement is large (>3000 units lipase/kg/meal)
consider use of a H2 blocker (acidity inactivates enzymes). Do not exceed 3000 units/lipase/kg/meal.
Doses > 20,000 units/kg/day increase risk of fibrosing colonopathy.
Product
Pancreaze® 4,200
10,500
16,800
21,000
Creon® 3,000
6,000
12,000
24,000
Zenpep® 3,000
5,000
10,000
15,000
20,000
Viokace® 10,440
20,880
Pertzye® 8,000
16,000
Ultresa® 13,800
20,700
23,000
Common Pancrelipase Products
Dosage Form
Lipase Units
Amylase Units
4,200
17,500
Capsule, enteric
10,500
43,750
coated microspheres
16,800
70,000
21,000
61,000
3,000
15,000
6,000
30,000
Capsule, enteric
coated microspheres
12,000
60,000
24,000
120,000
3,000
16,000
5,000
27,000
Capsule, enteric
10,000
55,000
coated microspheres
15,000
82,000
20,000
109,000
Tablet, non-enteric
10,440
39,150
coated
20,880
78,300
Capsules, enteric8,000
30,250
coated microtablets
16,000
60,500
Capsules, delayed13,800
27,600
release
20,700
41,400
23,000
46,000
Protease Units
10,000
25,000
40,000
37,000
9,500
19,000
38,000
76,000
10,000
17,000
34,000
51,000
68,000
39,150
78,300
28,750
57,500
27,600
41,400
46,000
Vitamin D Supplementation – Cholecalciferol
Age
Routine dosing with CF
specific vitamins (IU)
Step 1:
Step 2:
Dose increases (IU)
Dose titration maximum (IU)
25OH = 20-30 *
25OH = 10-20 *
Birth – 12 months
400 – 500
800 – 1,000
Not > 2,000
> 12 months – 10 yr
800 – 1,000
1,600 – 3,000
Not > 4,000
> 10 yr – 18 yr
800 – 2,000
1,600 – 6,000
Not > 10,000
> 18 yr
800 – 2,000
1,600 – 6,000
Not > 10,000
* Indicates total vitamin D (IU) intake per day, including Source CF vitamins
** Adapted from 2011 CF Update on Treatment of Vitamin D Deficiency
1 Source CF Softgel/Tablet = 1,000 units cholecalciferol
6
ADEK/SourceCF Vitamins: 1 SourceCF chew tab = 2 mL liquid SourceCF
< 1 yr: Liquid SourceCF vitamins 1 mL QDay
1-3 yr: Liquid SourceCF vitamins 2 mL QDay
May initiate chewable vitamins (1 QDay) at 2 yr
3-9 yr: SourceCF chewable vitamins 1 QDay
> 10 yr: SourceCF chewable vitamins 2 QDay
Vitamin K: For patients receiving oral or intravenous antibiotics
< 1 yr: 2.5 mg PO additional twice a week
> 1 yr: 5 mg PO additional twice a week
May require daily vitamin K if PT elevated at admit
Salt Supplement: Add supplemental salt to newborn and infant formula and food
< 6 months: 1/8 teaspoon per day
> 6 months – 1 yr: 1/4 teaspoon per day
Ursodiol: 10-15 mg/kg/dose PO BID
Azithromycin (Anti-inflammatory):
< 25 kg: 10 mg/kg/dose PO Q MWF
25 – 39kg: 250 mg PO Q MWF
> 40 kg: 500 mg PO Q MWF
References:
1. Zobell JT, Young DC, Waters CD, et al. Optimization of anti-pseudomonal antibiotics for cystic fibrosis
pulmonary exacerbations: VI. Executive summary. Pediatr Pulmonol. 2013;48:525-537.
2. Zobell JT, Young DC, Waters CD, et al. Optimization of anti-pseudomonal antibiotics for cystic fibrosis
pulmonary exacerbations: I. Aztreonam and carbapenems. Pediatr Pulmonol. 2012;47:1147-1158.
3. Zobell JT, Waters CD, Young DC, et al. Optimization of anti-pseudomonal antibiotics for cystic fibrosis
pulmonary exacerbations: II. Cephalosporins and penicillins. Pediatr Pulmonol. 2013;48:107-122.
4. Ceftaroline clinical trial
5. Stockmann C, Sherwin CMT, Zobell JT, et al. Optimization of anti-pseudomonal antibiotics for cystic
fibrosis pulmonary exacerbations: III. Fluoroquinolones. Pediatr Pulmonol. 2013;48:211-220.
6. Young DC, Zobell JT, Waters CD, et al. Optimization of anti-pseudomonal antibiotics for cystic fibrosis
pulmonary exacerbations: IV. Colistimethate sodium. Pediatr Pulmonol. 2013;48:1-7.
7. Flume PA, Mogayzel PJ, Robinson KA, et al. Cystic fibrosis pulmonary guidelines: treatment of
pulmonary exacerbations. Am J Respir Crit Care Med. 2009;180:802-808.
8. Trust UCF. Antibiotic treatment for cystic fibrosis in UK Cystic Fibrosis Trust Antibiotic Working Group.
2009.
9. Doring G, Conway SP, Heijerman HGM, et al. Antibiotic therapy against Pseudomonas aeruginosa in
cystic fibrosis: a European consensus. Eur Respir J. 2000;16:749-767.
10. Taketomo CK, Hodding JH, Kraus DM. Pediatric Dosage Handbook, 21st edition, 2014-2015.
11. Gibson RL, Burns JL, Ramsey BW. Pathophysiology and management of pulmonary infections in cystic
fibrosis. Am J Resp Crit Care Med 2003;168:918-51.
12. Chimel JF, Aksamit TR, Chotirmall SH, et al. Antibiotic management of lung infections in cystic fibrosis:
II. Nontuberculous mycobacteria, anaerobic bacteria, and fungi. Ann Am Thorac Soc. 2014;11(8):12981306.
13. Wallace RJ, et al. Clinical experience in 52 patients with tigecycline-containing regimens for salvage
treatment of Mycobacterium abscessus and Mycobacterium chelonae infections. J Antimicrob Chemother.
2014;69:1945-1953.
14. An official ATS/IDSA statement: Diagnosis, treatment, and prevention of nontuberculous mycobacterial
disease. Am J Respir Crit Care Med. 2007;175:367-416.
15. Andes D, Pascual A, Marchetti O: Antifungal therapeutic drug monitoring: established and emerging
indications. Antimicrob Agents Chemother 2009;53(1):24-34.
16. Hope WW, Billaud EM, Lestner J, Denning DW: Therapeutic drug monitoring for triazoles. Curr Opin
Infect Dis 2008;21:580-586.
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17. Pascual A et al. Voriconazole TDM in patients with invasive mycoses improves efficacy and safety
outcomes. CID 2008;45:201-211.
18. Scott LJ, Simpson D. Voriconazole: a review of its use in the management of invasive fungal infections.
Drugs 2007;67:269--98.
19. Bernardo VA, Cross SJ, Crews KR, et al. Posaconazole therapeutic drug monitoring in pediatric patients
and young adults with cancer. Ann Pharmacother. 2013;47(7-8):976-983.
Revised 5/15
Cameron Jordan, PharmD, BCPS
8